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Clerici M, Ciardulli MC, Lamparelli EP, Lovecchio J, Giordano E, Dale TP, Forsyth NR, Maffulli N, Della Porta G. Human tendon stem/progenitor cell-derived extracellular vesicle production promoted by dynamic culture. ARTIFICIAL CELLS, NANOMEDICINE, AND BIOTECHNOLOGY 2025; 53:1-16. [PMID: 40063517 DOI: 10.1080/21691401.2025.2475099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 11/14/2024] [Accepted: 02/24/2025] [Indexed: 05/13/2025]
Abstract
Tendon injuries significantly impact quality of life, prompting the exploration of innovative solutions beyond conventional surgery. Extracellular Vesicles (EVs) have emerged as a promising strategy to enhance tendon regeneration. In this study, human Tendon Stem/Progenitor Cells (TSPCs) were isolated from surgical biopsies and cultured in a Growth-Differentiation Factor-5-supplemented medium to promote tenogenic differentiation under static and dynamic conditions using a custom-made perfusion bioreactor. Once at 80% confluence, cells were transitioned to a serum-free medium for conditioned media collection. Ultracentrifugation revealed the presence of vesicles with a 106 particles/mL concentration and sub-200nm diameter size. Dynamic culture yielded a 3-fold increase in EV protein content compared to static culture, as confirmed by Western-blot analysis. Differences in surface marker expression were also shown by flow cytometric analysis. Data suggest that we efficiently developed a protocol for extracting EVs from human TSPCs, particularly under dynamic conditions. This approach enhances EV protein content, offering potential therapeutic benefits for tendon regeneration. However, further research is needed to fully understand the role of EVs in tendon regeneration.
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Affiliation(s)
- Marta Clerici
- Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, Salerno, Italy
- School of Pharmacy and Bioengineering, Keele University, Stoke-on-Trent, UK
| | - Maria Camilla Ciardulli
- Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, Salerno, Italy
| | - Erwin Pavel Lamparelli
- Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, Salerno, Italy
| | - Joseph Lovecchio
- School of Science and Engineering, Reykjavík University, Reykjavík, Iceland
- Institute of Biomedical and Neural Engineering, Reykjavik University, Reykjavík, Iceland
| | - Emanuele Giordano
- Department of Electrical, Electronic and Information Engineering "Guglielmo Marconi" (DEI), University of Bologna, Cesena, Italy
| | - Tina P Dale
- School of Pharmacy and Bioengineering, Keele University, Stoke-on-Trent, UK
| | - Nicholas R Forsyth
- School of Pharmacy and Bioengineering, Keele University, Stoke-on-Trent, UK
- Vice Principals' Office, University of Aberdeen, Kings College, Aberdeen, UK
| | - Nicola Maffulli
- School of Pharmacy and Bioengineering, Keele University, Stoke-on-Trent, UK
- Department of Trauma and Orthopaedics, Faculty of Medicine and Psychology, Sant'Andrea Hospital, Sapienza University, Rome, Italy
| | - Giovanna Della Porta
- Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, Salerno, Italy
- Interdepartmental Centre BIONAM, University of Salerno, Fisciano, Salerno, Italy
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2
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Li L, Xu X, Cheng P, Yu Z, Li M, Yu Z, Cheng W, Zhang W, Sun H, Song X. Klebsiella pneumoniae derived outer membrane vesicles mediated bacterial virulence, antibiotic resistance, host immune responses and clinical applications. Virulence 2025; 16:2449722. [PMID: 39792030 PMCID: PMC11730361 DOI: 10.1080/21505594.2025.2449722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 11/14/2024] [Accepted: 12/28/2024] [Indexed: 01/12/2025] Open
Abstract
Klebsiella pneumoniae is a gram-negative pathogen that can cause multiple diseases including sepsis, urinary tract infections, and pneumonia. The escalating detections of hypervirulent and antibiotic-resistant isolates are giving rise to growing public concerns. Outer membrane vesicles (OMVs) are spherical vesicles containing bioactive substances including lipopolysaccharides, peptidoglycans, periplasmic and cytoplasmic proteins, and nucleic acids. Emerging studies have reported various roles of OMVs in bacterial virulence, antibiotic resistance, stress adaptation, and host interactions, whereas knowledge on their roles in K. pneumoniae is currently unclear. In this review, we summarized recent progress on the biogenesis, components, and biological function of K. pneumoniae OMVs, the impact and action mechanism in virulence, antibiotic resistance, and host immune response. We also deliberated on the potential of K. pneumoniae OMVs in vaccine development, as diagnostic biomarkers, and as drug nanocarriers. In conclusion, K. pneumoniae OMVs hold great promise in the prevention and control of infectious diseases, which merits further investigation.
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Affiliation(s)
- Lifeng Li
- Henan International Joint Laboratory of Children’s Infectious Diseases, Department of Neonatology, Henan Province Engineering Research Center of Diagnosis and Treatment of Pediatric Infection and Critical Care, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, China
| | - Xinxiu Xu
- Department of Neurology, Qingdao Hospital, University of Health and Rehabilitation Sciences, Qingdao, China
| | - Ping Cheng
- Henan International Joint Laboratory of Children’s Infectious Diseases, Department of Neonatology, Henan Province Engineering Research Center of Diagnosis and Treatment of Pediatric Infection and Critical Care, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, China
| | - Zengyuan Yu
- Henan International Joint Laboratory of Children’s Infectious Diseases, Department of Neonatology, Henan Province Engineering Research Center of Diagnosis and Treatment of Pediatric Infection and Critical Care, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, China
| | - Mingchao Li
- Henan International Joint Laboratory of Children’s Infectious Diseases, Department of Neonatology, Henan Province Engineering Research Center of Diagnosis and Treatment of Pediatric Infection and Critical Care, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, China
| | - Zhidan Yu
- Henan International Joint Laboratory of Children’s Infectious Diseases, Department of Neonatology, Henan Province Engineering Research Center of Diagnosis and Treatment of Pediatric Infection and Critical Care, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, China
| | - Weyland Cheng
- Henan International Joint Laboratory of Children’s Infectious Diseases, Department of Neonatology, Henan Province Engineering Research Center of Diagnosis and Treatment of Pediatric Infection and Critical Care, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, China
| | - Wancun Zhang
- Henan International Joint Laboratory of Children’s Infectious Diseases, Department of Neonatology, Henan Province Engineering Research Center of Diagnosis and Treatment of Pediatric Infection and Critical Care, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, China
| | - Huiqing Sun
- Henan International Joint Laboratory of Children’s Infectious Diseases, Department of Neonatology, Henan Province Engineering Research Center of Diagnosis and Treatment of Pediatric Infection and Critical Care, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, China
| | - Xiaorui Song
- Henan International Joint Laboratory of Children’s Infectious Diseases, Department of Neonatology, Henan Province Engineering Research Center of Diagnosis and Treatment of Pediatric Infection and Critical Care, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, China
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3
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Woo HK, Nam Y, Park HG, Lee H. Bridging laboratory innovation to translational research and commercialization of extracellular vesicle isolation and detection. Biosens Bioelectron 2025; 282:117475. [PMID: 40300344 PMCID: PMC12076185 DOI: 10.1016/j.bios.2025.117475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 03/04/2025] [Accepted: 04/13/2025] [Indexed: 05/01/2025]
Abstract
Extracellular vesicles (EVs) have emerged as promising biomarkers for various diseases. Encapsulating biomolecules reflective of their parental cells, EVs are readily accessible in bodily fluids. The prospect for minimally invasive, repeatable molecular testing has stimulated significant research; however, challenges persist in isolating EVs from complex biological matrices and characterizing their limited molecular cargo. Technical advances have been pursued to address these challenges, producing innovative EV-specific platforms. This review highlights recent technological developments, focusing on EV isolation and molecular detection methodologies. Furthermore, it explores the translation of these laboratory innovations to clinical applications through the analysis of patient samples, providing insights into the potential diagnostic and prognostic utility of EV-based technologies.
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Affiliation(s)
- Hyun-Kyung Woo
- Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Yoonho Nam
- Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Chemical and Biomolecular Engineering (BK21 Four), Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea
| | - Hyun Gyu Park
- Department of Chemical and Biomolecular Engineering (BK21 Four), Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
| | - Hakho Lee
- Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
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Kim MG, Ryu SM, Shin Y. Recent advances in bioreceptor-based sensing for extracellular vesicle analysis. Biosens Bioelectron 2025; 280:117432. [PMID: 40187151 DOI: 10.1016/j.bios.2025.117432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 03/07/2025] [Accepted: 03/31/2025] [Indexed: 04/07/2025]
Abstract
Extracellular vesicles (EVs) are nanoscale, membrane-bound structures secreted by various cell types into biofluids. They show great potential as biomarkers for disease diagnostics, owing to their ability to carry molecular cargo that reflects their cellular origin. However, the inherent heterogeneity of EVs in terms of size, composition, and source presents significant challenges for reliable detection and analysis. Recent advances in bioreceptor-based biosensor technologies provide promising solutions by offering high sensitivity and specificity in EV detection and characterization. These technologies address the limitations of conventional methods, such as ultracentrifugation and bulk analysis. Biosensors utilizing antibodies, aptamers, peptides, lectins, and molecularly imprinted polymers enable precise detection of EV subpopulations by targeting specific EV surface markers, including proteins, lipids, and glycans. Additionally, these biosensors support multiplexed and real-time analysis while preserving the structural integrity of EVs. This review highlights the transformative potential of combining modern biosensing tools with bioreceptor technologies to advance EV research and diagnostics, paving the way for innovations in disease diagnostics and therapeutic monitoring.
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Affiliation(s)
- Myoung Gyu Kim
- Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei Ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Soo Min Ryu
- Life Science and Biotechnology, Underwood International College, Yonsei University, 50 Yonsei Ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Yong Shin
- Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei Ro, Seodaemun-gu, Seoul, 03722, Republic of Korea; Life Science and Biotechnology, Underwood International College, Yonsei University, 50 Yonsei Ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
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5
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Bavafa A, Izadpanahi M, Hosseini E, Hajinejad M, Abedi M, Forouzanfar F, Sahab-Negah S. Exosome: an overview on enhanced biogenesis by small molecules. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:6473-6508. [PMID: 39862264 DOI: 10.1007/s00210-024-03762-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Accepted: 12/23/2024] [Indexed: 01/27/2025]
Abstract
Exosomes are extracellular vesicles that received attention for their potential use in the treatment of various injuries. They communicate intercellularly by transferring genetic and bioactive molecules from parent cells. Although exosomes hold immense promise for treating neurodegenerative and oncological diseases, their actual clinical use is very limited because of their biogenesis and secretion. Recent studies have shown that small molecules can significantly enhance exosome biogenesis, thereby remarkably improving yield, functionality, and therapeutic effects. These molecules modulate critical pathways toward optimum exosome production in a mode that is either ESCRT dependent or ESCRT independent. Improved exosome biogenesis may provide new avenues for targeted cancer therapy, neuroprotection in neurodegenerative diseases, and regenerative medicine in wound healing. This review explores the role of small molecules in enhancing exosome biogenesis and secretion, highlights their underlying mechanisms, and discusses emerging clinical applications. By addressing current challenges and focusing on translational opportunities, this study provides a foundation for advancing cell-free therapies in regenerative medicine and beyond.
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Affiliation(s)
- Amir Bavafa
- Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Neuroscience, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Maryam Izadpanahi
- Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Neuroscience, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Elham Hosseini
- Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Neuroscience, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mehrdad Hajinejad
- Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Qaen Faculty of Medical Sciences, Birjand University of Medical Sciences, Birjand, Iran
| | - Mahsa Abedi
- Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Institute for Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany
| | - Fatemeh Forouzanfar
- Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- Department of Neuroscience, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Sajad Sahab-Negah
- Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- Department of Neuroscience, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
- Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran.
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6
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Zhang L, Wong CY, Shao H. Integrated technologies for molecular profiling of genetic and modified biomarkers in extracellular vesicles. LAB ON A CHIP 2025; 25:2504-2520. [PMID: 40135945 DOI: 10.1039/d5lc00053j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/27/2025]
Abstract
Extracellular vesicles (EVs) are nanoscale membrane vesicles actively released by cells into a variety of biofluids. EVs carry myriad molecular cargoes; these include classical genetic biomarkers inherited from the parent cells as well as EV modifications by other entities (e.g., small molecule drugs). Aided by these diverse cargoes, EVs enable long-distance intercellular communication and have been directly implicated in various disease pathologies. As such, EVs are being increasingly recognized as a source of valuable biomarkers for minimally-invasive disease diagnostics and prognostics. Despite the clinical potential, EV molecular profiling remains challenging, especially in clinical settings. Due to the nanoscale dimension of EVs as well as the abundance of contaminants in biofluids, conventional EV detection methods have limited resolution, require extensive sample processing and can lose rare biomarkers. To address these challenges, new micro- and nanotechnologies have been developed to discover EV biomarkers and empower clinical applications. In this review, we introduce EV biogenesis for different cargo incorporation, and discuss the use of various EV biomarkers for clinical applications. We also assess different chip-based integrated technologies developed to measure genetic and modified biomarkers in EVs. Finally, we highlight future opportunities in technology development to facilitate the clinical translation of various EV biomarkers.
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Affiliation(s)
- Li Zhang
- Institute for Health Innovation & Technology, National University of Singapore, MD6, 14 Medical Drive #14-01, Singapore 117599, Singapore.
| | - Chi Yan Wong
- Institute for Health Innovation & Technology, National University of Singapore, MD6, 14 Medical Drive #14-01, Singapore 117599, Singapore.
| | - Huilin Shao
- Institute for Health Innovation & Technology, National University of Singapore, MD6, 14 Medical Drive #14-01, Singapore 117599, Singapore.
- Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore 117583, Singapore
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
- Department of Materials Science and Engineering, College of Design and Engineering, National University of Singapore, Singapore 117575, Singapore
- Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673, Singapore
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7
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Nadeau A, Tsering T, Abdouh M, Kienzle L, Cleyle J, Taylor L, Douanne N, Dickinson K, Siegel PM, Burnier JV. Characterization of extracellular vesicle-associated DNA and proteins derived from organotropic metastatic breast cancer cells. J Exp Clin Cancer Res 2025; 44:157. [PMID: 40410902 PMCID: PMC12100931 DOI: 10.1186/s13046-025-03418-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2025] [Accepted: 05/12/2025] [Indexed: 05/25/2025] Open
Abstract
BACKGROUND While primary breast cancer (BC) is often effectively managed, metastasis remains the primary cause of BC-related fatalities. Gaps remain in our understanding of the mechanisms regulating cancer cell organotropism with predilection to specific organs. Unraveling mediators of site-specific metastasis could enhance early detection and enable more tailored interventions. Liquid biopsy represents an innovative approach in cancer involving the analysis of biological materials such as circulating tumor DNA and tumor-derived extracellular vesicles (EV) found in body fluids like blood or urine. This offers valuable insights for characterizing and monitoring tumor genomes to advance personalized medicine in metastatic cancers. METHODS We performed in-depth analyses of EV cargo associated with BC metastasis using eight murine cell line models with distinct metastatic potentials and organotropism to the lung, the bone, the liver, and the brain. We characterized the secretome of these cells to identify unique biomarkers specific to metastatic sites. RESULTS Small EVs isolated from all cell lines were quantified and validated for established EV markers. Tracking analysis and electron microscopy revealed EV secretion patterns that differed according to cell line. Cell-free (cf)DNA and EV-associated DNA (EV-DNA) were detected from all cell lines with varying concentrations. We detected a TP53 mutation in both EV-DNA and cfDNA. Mass spectrometry-based proteomics analyses identified 698 EV-associated proteins, which clustered according to metastatic site. This analysis highlighted both common EV signatures and proteins involved in cancer progression and organotropism unique to metastatic cell lines. Among these, 327 significantly differentially enriched proteins were quantified with high confidence levels across BC and metastatic BC cells. We found enrichment of specific integrin receptors in metastatic cancer EVs compared to EVs secreted from non-transformed epithelial cells and matched tumorigenic non-metastatic cells. Pathway analyses revealed that EVs derived from parental cancer cells display a cell adhesion signature and are enriched with proteins involved in cancer signaling pathways. CONCLUSION Taken together, the characterization of EV cargo in a unique model of BC organotropism demonstrated that EV-DNA and EV proteomes were informative of normal and cancer states. This work could help to identify BC biomarkers associated with site-specific metastasis and new therapeutic targets.
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Affiliation(s)
- Amélie Nadeau
- Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
- Department of Pathology, McGill University, Montreal, QC, Canada
| | - Thupten Tsering
- Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
- Department of Pathology, McGill University, Montreal, QC, Canada
| | - Mohamed Abdouh
- Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
| | - Laura Kienzle
- Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
| | - Jenna Cleyle
- Centre for Translational Biology, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
| | - Lorne Taylor
- Centre for Translational Biology, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
| | - Noélie Douanne
- Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
- Department of Pathology, McGill University, Montreal, QC, Canada
| | - Kyle Dickinson
- Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
| | - Peter M Siegel
- Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, QC, Canada
- Department of Medicine, McGill University, Montreal, QC, Canada
| | - Julia V Burnier
- Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
- Department of Pathology, McGill University, Montreal, QC, Canada.
- Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, QC, Canada.
- Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada.
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8
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Liu C, Cheng C, Cheng K, Gao AS, Li Q, Atala A, Zhang Y. Precision exosome engineering for enhanced wound healing and scar revision. J Transl Med 2025; 23:578. [PMID: 40410904 PMCID: PMC12103044 DOI: 10.1186/s12967-025-06578-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2025] [Accepted: 05/05/2025] [Indexed: 05/25/2025] Open
Abstract
The dysfunction of wound-healing processes can result in chronic non-healing wounds and pathological scar formation. Current treatment options often fall short, necessitating innovative approaches. Exosomes, extracellular vesicles secreted by various cells, have emerged as promising therapeutic agents serving as an intercellular communication system. By engineering exosomes, their cargo and surface properties can be tailored to enhance therapeutic efficacy and specificity. Engineered exosomes (eExo) are emerging as a favorable tool for treating non-healing wounds and pathological scars. In this review, we delve into the underlying mechanisms of non-healing wounds and pathological scars, outline the current state of engineering strategies, and explore the clinical potential of eExo based on preclinical and clinical studies. In addition, we address the current challenges and future research directions, including standardization, safety and efficacy assessments, and potential immune responses. In conclusion, eExo hold great promise as a novel therapeutic approach for non-healing wounds and non-healing wounds and pathological scars. Further research and clinical trials are warranted to translate preclinical findings into effective clinical treatments.
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Affiliation(s)
- Chuanqi Liu
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China
| | - Chen Cheng
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China
| | - Kun Cheng
- Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, 64108-2718, USA
| | - Allen S Gao
- Department of Urologic Surgery, School of Medicine, University of California, Davis Sacramento, CA, 95817, USA
| | - Qingfeng Li
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.
| | - Anthony Atala
- Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC, 27151, USA
| | - Yuanyuan Zhang
- Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC, 27151, USA.
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9
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Asgari R, Rashidi S, Soleymani B, Bakhtiari M, Mohammadi P, Yarani R, Mansouri K. The supportive role of stem cells-derived exosomes in the embryo implantation process by regulating oxidative stress. Biomed Pharmacother 2025; 188:118171. [PMID: 40412359 DOI: 10.1016/j.biopha.2025.118171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2025] [Revised: 04/28/2025] [Accepted: 05/10/2025] [Indexed: 05/27/2025] Open
Abstract
Oxidative stress can affect many aspects of the reproduction process. The embryo implantation process is also one of the critical steps in establishing a successful pregnancy, and several factors, including oxidative stress, can impact the process. Oxidative stress is a state of imbalance between pro-oxidant molecules such as reactive oxygen species (ROS) and antioxidant defenses. Excessive levels of ROS cause damage to the cellular macromolecules such as nucleic acids, proteins, and lipids, resulting in cell dysfunction and pathological conditions. Recently, studies have displayed the therapeutic and antioxidant properties of exosomes derived from stem cells. Exosomes are one type of extracellular vesicles (EVs) secreted by almost all cells and contain different biomolecules. The unique properties of exosomes, like regulation of biological processes, transportation of biomolecules, stability, and biodegradability, can make exosomes a promising therapeutic option in reproductive disorders and diseases. Exosomes also can significantly improve the curative effect of oxidative stress-related pathogenesis. Accordingly, this review aims to provide a novel overview of how exosomes derived from stem cells can regulate oxidative stress and support the process of embryo implantation, hoping to pave the way to clinical applications and future research in this field.
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Affiliation(s)
- Rezvan Asgari
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Sahar Rashidi
- Department of Obstetrics and Gynecology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Bijan Soleymani
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mitra Bakhtiari
- Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Pantea Mohammadi
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Reza Yarani
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; Translational Type 1 Diabetes Research, Department of Clinical, Research, Steno Diabetes Center Copenhagen, Gentofte, Denmark
| | - Kamran Mansouri
- Regenerative Medicine Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
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10
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Liu Q, Liu M, Lu W, Li H, Ma Z, Xiong J, Zhang P. Surface-enhanced confocal Raman microscopy to characterize esophageal cancer cell-derived extracellular vesicles and maternal cells. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2025; 17:4167-4175. [PMID: 40353506 DOI: 10.1039/d4ay02300e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/14/2025]
Abstract
Exosomes, a subtype of extracellular vesicles, are increasingly recognized as promising biomarkers for human cancers. Rapid detection and classification of esophageal cancer-associated exosomes could significantly improve non-invasive screening for potential patients. This study aims to establish a label-free, direct surface-enhanced Raman scattering (SERS) method to capture characteristic molecular information from both esophageal cancer cells and their corresponding exosomes using confocal Raman microscopy. The results revealed distinct Raman spectra for esophageal cancer cells and their exosomes within the range of 500-1600 cm-1, with notable signal similarities observed at 506-622, 778-832, 1079-1098, and 1572-1630 cm-1. In contrast, significant differences were identified in Raman peaks related to nucleic acids (723, 654, 1354 cm-1) and proteins (998, 1028, 1354, 1560 cm-1). An orthogonal partial least squares discriminant analysis (OPLS-DA) model was utilized to discern subtle variations among these highly similar samples, achieving an accuracy rate of 100%. By comparing the spectral correlations between esophageal cancer cells and their exosomes, this study provides valuable insights into the molecular composition and cellular origins of exosomes. The findings demonstrate the potential of integrating SERS with OPLS-DA for the precise and rapid detection and monitoring of esophageal cancer through exosomal biomarkers, offering a powerful tool for diagnostic applications.
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Affiliation(s)
- Qianjin Liu
- College of Future Technology, State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100871, China.
| | - Mengdong Liu
- College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China.
| | - Wenjing Lu
- College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China.
| | - Han Li
- College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China.
| | - Zixuan Ma
- College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China.
| | - Jingwei Xiong
- College of Future Technology, State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100871, China.
| | - Ping Zhang
- College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China.
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11
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Kang H, Qiu L, Li Y, Xu X, Pei R, Yang T, Yang L, Xu X, Sun N. Si Microanemones Integrated Microfluidic Chip for Highly Efficient Isolation of Extracellular Vesicles. Adv Healthc Mater 2025:e2500439. [PMID: 40395100 DOI: 10.1002/adhm.202500439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2025] [Revised: 04/29/2025] [Indexed: 05/22/2025]
Abstract
Liquid biopsy has emerged as a transformative approach for early cancer detection and treatment monitoring, offering significant potential to improve patient outcomes. However, isolating tumor-derived extracellular vesicles (EVs) from body fluids is often impeded by background noise, making subsequent analysis challenging. Herein, a bio-inspired 3D silicon microanemone (SMA) microfluidic chip is reported. This innovative structure is prepared by a two-step lithographic method combined with nanosphere lithography, achieving an impressive isolation efficiency of 89.4%. Simulation results reveal that the hierarchical structure not only provides more antibody binding sites but also synergizes with an integrated chaotic mixer to amplify fluid perturbations, while inducing a flow around circular cylinder phenomenon to enhance EV-antibody interactions. Finally, the SMA chip's performance is assessed with clinical samples and combined with RT-qPCR-based β-actin (ACTB) mRNA quantification in purified EVs. The results demonstrate its high sensitivity and specificity in isolating cancer-related EV subgroups, enabling non-invasive and precise detection of cancer biomarkers in blood samples.
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Affiliation(s)
- Hanyue Kang
- Key Laboratory of Advanced Civil Engineering Materials of Ministry of Education, Key Laboratory of D&A for Metal-Functional Materials, School of Materials Science & Engineering, Tongji University, Shanghai, 201804, China
| | - Lei Qiu
- Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Suzhou, 215123, China
- School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei, 230026, China
| | - Yecheng Li
- Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215000, China
| | - Xiaocheng Xu
- Department of Thyroid and Breast Surgery, Suzhou Ninth People's Hospital, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, 215000, China
| | - Renjun Pei
- Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Suzhou, 215123, China
- School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei, 230026, China
| | - Tongqing Yang
- Key Laboratory of Advanced Civil Engineering Materials of Ministry of Education, Key Laboratory of D&A for Metal-Functional Materials, School of Materials Science & Engineering, Tongji University, Shanghai, 201804, China
| | - Lizhi Yang
- Zhejiang Dongfang Polytechnic School of Health Medicine, Wenzhou, Zhejiang, 325000, China
| | - Xiaobin Xu
- Key Laboratory of Advanced Civil Engineering Materials of Ministry of Education, Key Laboratory of D&A for Metal-Functional Materials, School of Materials Science & Engineering, Tongji University, Shanghai, 201804, China
| | - Na Sun
- Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Suzhou, 215123, China
- School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei, 230026, China
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12
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Picchio V, Pontecorvi V, Dhori X, Bordin A, Floris E, Cozzolino C, Frati G, Pagano F, Chimenti I, De Falco E. The emerging role of artificial intelligence applied to exosome analysis: from cancer biology to other biomedical fields. Life Sci 2025; 375:123752. [PMID: 40409585 DOI: 10.1016/j.lfs.2025.123752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2025] [Revised: 05/06/2025] [Accepted: 05/20/2025] [Indexed: 05/25/2025]
Abstract
In recent years, exosomes versatility has prompted their study in the biomedical field for diagnostic, prognostic, and therapeutic applications. Exosomes are bi-lipid small extracellular vesicles (30-150 nm) secreted by various cell types, containing proteins, lipids, and DNA/RNA. They mediate intercellular communication and can influence multiple human physiological and pathological processes. So far, exosome analysis has revealed their role as promising diagnostic tools for human pathologies. Concurrently, artificial intelligence (AI) has revolutionised multiple sectors, including medicine, owing to its ability to analyse large datasets and identify complex patterns. The combination of exosome analysis with AI processing has displayed a novel diagnostic approach for cancer and other diseases. This review explores the current applications and prospects of the combined use of exosomes and AI in medicine. Firstly, we provide a biological overview of exosomes and their relevance in cancer biology. Then we explored exosome isolation techniques and Raman spectroscopy/SERS analysis. Finally, we present a summarised essential guide of AI methods for non-experts, emphasising the advancements made in AI applications for exosome characterisation and profiling in oncology research, as well as in other human diseases.
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Affiliation(s)
- Vittorio Picchio
- Department of Angio Cardio Neurology, IRCCS Neuromed, 86077 Pozzilli, Italy
| | - Virginia Pontecorvi
- Department of Medical Surgical Sciences and Biotechnologies, Sapienza University, 04100 Latina, Italy
| | - Xhulio Dhori
- CINECA, Super Computing Applications and Innovation Department, 000185 Roma, Italy
| | - Antonella Bordin
- Department of Medical Surgical Sciences and Biotechnologies, Sapienza University, 04100 Latina, Italy
| | - Erica Floris
- Department of Medical Surgical Sciences and Biotechnologies, Sapienza University, 04100 Latina, Italy
| | - Claudia Cozzolino
- Department of Medical Surgical Sciences and Biotechnologies, Sapienza University, 04100 Latina, Italy
| | - Giacomo Frati
- Department of Angio Cardio Neurology, IRCCS Neuromed, 86077 Pozzilli, Italy; Department of Medical Surgical Sciences and Biotechnologies, Sapienza University, 04100 Latina, Italy
| | - Francesca Pagano
- Institute of Biochemistry and Cell Biology, National Council of Research (IBBC-CNR), 00015 Monterotondo,Italy
| | - Isotta Chimenti
- Department of Angio Cardio Neurology, IRCCS Neuromed, 86077 Pozzilli, Italy; Department of Medical Surgical Sciences and Biotechnologies, Sapienza University, 04100 Latina, Italy; CINECA, Super Computing Applications and Innovation Department, 000185 Roma, Italy; Institute of Biochemistry and Cell Biology, National Council of Research (IBBC-CNR), 00015 Monterotondo,Italy; Maria Cecilia Hospital, GVM Care & Research, 48033 Cotignola, Italy.
| | - Elena De Falco
- Department of Angio Cardio Neurology, IRCCS Neuromed, 86077 Pozzilli, Italy; Department of Medical Surgical Sciences and Biotechnologies, Sapienza University, 04100 Latina, Italy; CINECA, Super Computing Applications and Innovation Department, 000185 Roma, Italy; Institute of Biochemistry and Cell Biology, National Council of Research (IBBC-CNR), 00015 Monterotondo,Italy; Maria Cecilia Hospital, GVM Care & Research, 48033 Cotignola, Italy
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13
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Zhang Y, Wang C, Shao H. Nanoplasmonic Sensing of Heterogeneous Extracellular Vesicles: From Bulk to Single Vesicles. SMALL METHODS 2025:e2500097. [PMID: 40391615 DOI: 10.1002/smtd.202500097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 04/16/2025] [Indexed: 05/22/2025]
Abstract
Extracellular vesicles (EVs) are heterogeneous nanoscale membrane vesicles released by almost all cell types into the circulation. Depending on their biogenesis and cells of origin, EVs show considerable heterogeneity in their biophysical and biomolecular composition and can serve as reflective and dynamic blood biomarkers for personalized medicine. Conventional analytical technologies, however, often lack the compatibility to reveal nanoscale EV features and resolve vesicle heterogeneity. The past decade has since witnessed the development of various nanoplasmonic technologies to empower EV analysis, through bulk and single-vesicle characterization, at an unprecedented scale and resolution. These platforms achieve versatile measurements that are not only size-matched to EV dimensions but can also probe multiplexed biomolecular contents, thereby providing new insights into EV heterogeneity and enabling transformative clinical opportunities. In this review, key characteristics of EVs and their remarkable heterogeneity are introduced. The sensing principles of plasmonic platforms are also discussed, with recent technology developments highlighted to resolve EV heterogeneity, through bulk analyses of EV subpopulations as well as high-resolution single-EV measurements. An outlook is further provided on emerging opportunities, at the interface of biomarker discovery and technology innovation, to develop empowering nanoplasmonic EV platforms for personalized medicine. biosensing; bulk analysis; extracellular vesicles; nanoplasmonics; single-vesicle analysis.
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Affiliation(s)
- Yan Zhang
- Institute for Health Innovation & Technology, National University of Singapore, Singapore, 117599, Singapore
- Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore, 117583, Singapore
| | - Chao Wang
- Institute for Health Innovation & Technology, National University of Singapore, Singapore, 117599, Singapore
- Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore, 117583, Singapore
| | - Huilin Shao
- Institute for Health Innovation & Technology, National University of Singapore, Singapore, 117599, Singapore
- Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore, 117583, Singapore
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore
- Department of Materials Science and Engineering, College of Design and Engineering, National University of Singapore, Singapore, 117575, Singapore
- Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, 138673, Singapore
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14
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Dai X, Huang H, Liu F. Rapid Identification of Esophageal Squamous Cell Carcinoma Biomarkers by MALDI-TOF MS Fingerprinting of Extracellular Vesicles. Anal Chem 2025; 97:10180-10189. [PMID: 40326690 DOI: 10.1021/acs.analchem.4c06273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/07/2025]
Abstract
Esophageal cancer is a major global health challenge, with high incidence and mortality due to the lack of rapid and sensitive diagnostic tools and specific biomarkers. Cancer-cell-derived extracellular vesicles (EVs) carry unique proteins and nucleic acids, making them valuable sources of cancer biomarkers. We report an integrated method that combines an ultrafast exosome isolation system (EXODUS) with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to detect EVs and identify protein biomarkers for diagnosing and monitoring esophageal squamous cell carcinoma (ESCC). EVs derived from 20 mL culture medium supernatant of ESCC cells with varying degrees of differentiation serve as analysis models. We use EXODUS to isolate EVs rapidly. We then analyze the intact EVs using MALDI-TOF MS, which provides cell line-specific EV fingerprints in minutes. These protein fingerprints allow the discrimination of ESCC from normal control cells and enable the classification of ESCC based on the degree of cell differentiation. We explore critical EV biomarker peaks for ESCC diagnosis (5555 m/z, 8603 m/z, etc.) and monitoring (2268 m/z, etc.). Potential EV biomarker candidates, including YBX1, DIRAS2, HIST1H2AH, and MYBBP1A, are identified through tandem mass tag (TMT) proteomics. We tentatively assign the protein identities of EV marker peaks by correlation with the TMT proteomics. Applying this method to plasma-derived EVs shows promise for rapid, minimally invasive diagnosis and monitoring of ESCC.
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Affiliation(s)
- Xiaodan Dai
- National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
| | - Huiying Huang
- National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
| | - Fei Liu
- National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
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15
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Islam MKB, Marcus RK. Effects of packing density and adsorption conditions on extracellular vesicle dynamic binding capacities for capillary-channeled polymer (C-CP) fiber columns. J Chromatogr A 2025; 1755:466068. [PMID: 40403650 DOI: 10.1016/j.chroma.2025.466068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2025] [Revised: 05/16/2025] [Accepted: 05/17/2025] [Indexed: 05/24/2025]
Abstract
Extracellular vesicles (EVs) are membrane-bound nanoparticles (50-1000 nm) secreted by all cell types and play critical roles in various biological processes. Among these, exosomes, a smaller subset of EVs, have attracted considerable interest due to their potential applications in diagnostics and therapeutics. However, conventional EV isolation methods are often limited by inefficiencies in processing time, recovery, and scalability. Hydrophobic interaction chromatography utilizing capillary-channeled polymer (CCP) fiber stationary phases offers a promising alternative, enabling rapid (<15 min), cost-effective (∼$5 per column) EV isolation with high loading capacities (∼1010-10¹² particles) and minimal sample pre-processing. Despite these advantages, achieving high-throughput EV isolation for larger-scale applications using the CCP fiber platform is the present challenge. To this end, further optimization of stationary phase packing and adsorption conditions is necessary to maximize the available binding surface area in the current microbore column format. This study systematically investigates the influence of interstitial fraction (i.e. packing density) in polyester (PET) CCP fiber columns on the dynamic binding capacity (DBC) of EVs isolated from human urine using a high-performance liquid chromatography platform. Microbore columns (0.76 mm i.d. × 300 mm) packed with PET CCP fibers in both an eight-channel (PET-8) and a novel trilobal (PET-Y) configuration were evaluated using breakthrough curves and frontal analysis. The results reveal that lower packing densities correlate with higher mass- and surface area-based EV binding capacities, with a maximum DBCs of 2.86 × 10¹³ EVs g-1 fiber and 1.22 × 10¹⁴ EVs m⁻² fiber achieved in <2 min of sample loading. Under optimum conditions, surface utilization of >50 % is realized. These results establish a framework for optimizing CCP fiber-based platforms to enhance EV capture efficiency, facilitating the development of scalable EV isolation techniques for biomedical research and therapeutic applications.
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Affiliation(s)
- Md Khalid Bin Islam
- Department of Chemistry, Biosystems Research Complex, Clemson University, Clemson, SC 29634-0973, USA
| | - R Kenneth Marcus
- Department of Chemistry, Biosystems Research Complex, Clemson University, Clemson, SC 29634-0973, USA.
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16
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Wang H, Sun J, Zou Q, Du B, Liu H, Luan Y, Wang X, Yang X, Wang Q, Wang K. Wash-Free Isolation and Quantification of Tumor-Derived Exosomes via In Situ-Formed Hydrogel. ACS Sens 2025. [PMID: 40380946 DOI: 10.1021/acssensors.5c00204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/19/2025]
Abstract
The isolation and detection of exosomes as tumor markers are of vital importance for the early diagnosis, therapeutic monitoring, and mechanistic studies of tumors. Here, exosomes derived from breast cancer cells were chosen as model targets, and a wash-free, enzyme-free, handheld mini centrifugation method based on hydrogels was developed to effectively isolate and detect breast cancer exosomes. Dual aptamers (CD63-T1 and EpCAM-T2) were employed to specifically recognize and capture breast cancer exosomes. This specific recognition triggered the formation of hybridization chain reaction (HCR) nanostructures on the captured exosomes through the interaction of hairpin 1 and the alginate complex (H1-Alg) and hairpin 2 (H2-Cy3). The interaction of Ca2+ and alginate enabled the in situ formation of a hydrogel on the exosome surface. Subsequent low-speed centrifugation using a handheld mini centrifuge facilitated the efficient isolation of the exosomes, thereby eliminating the need for tedious washing steps. Utilizing the classical chelation reaction of ethylene diamine tetraacetic acid (EDTA) with Ca2+, the hydrogel can be rapidly cleaved for enzyme-free release of exosomes. The method demonstrated excellent capture and release efficiencies of approximately 85% and 98%, respectively, for specific cancerous exosomes. Notably, the exosomes isolated by the hydrogel system retained excellent biological activity, making them suitable for further analysis and potential applications. Meanwhile, the highly sensitive detection of breast cancer exosomes based on this strategy could also be achieved with a lower limit of detection as low as 3.2 × 103 particles/mL. This work provides a novel and cost-effective strategy for the effective isolation and detection of tumor-derived exosomes, which can help to promote the subsequent application of exosomes in research.
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Affiliation(s)
- Hongqiang Wang
- State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, PR China
| | - Jiayu Sun
- State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, PR China
| | - Qingqing Zou
- State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, PR China
| | - Bin Du
- State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, PR China
| | - Hui Liu
- State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, PR China
| | - Yanan Luan
- State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, PR China
| | - Xin Wang
- State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, PR China
| | - Xiaohai Yang
- State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, PR China
| | - Qing Wang
- State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, PR China
| | - Kemin Wang
- State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, PR China
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17
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Zhang X, Wang Y, E Q, Naveed M, Wang X, Liu Y, Li M. The biological activity and potential of probiotics-derived extracellular vesicles as postbiotics in modulating microbiota-host communication. J Nanobiotechnology 2025; 23:349. [PMID: 40380331 PMCID: PMC12082936 DOI: 10.1186/s12951-025-03435-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Accepted: 05/01/2025] [Indexed: 05/19/2025] Open
Abstract
Probiotics such as Lactobacillus and Bifidobacterium spp. have been shown to be critical for maintaining host homeostasis. In recent years, key compounds of postbiotics derived from probiotic metabolism and cellular secretion have been identified for their role in maintaining organ immunity and regulating intestinal inflammation. In particular, probiotic-derived extracellular vesicles (PEVs) can act as postbiotics, maintaining almost the same functional activity as probiotics. They also have strong biocompatibility and loading capacity to carry exogenous or parental active molecules to reach distal organs to play their roles. This provides a new direction for understanding the intrinsic microbiota-host communication mechanism. However, most current studies on PEVs are limited to their functional effects/benefits, and their specific physicochemical properties, composition, intrinsic mechanisms for maintaining host homeostasis, and possible threats remain to be explored. Here, we review and summarize the unique physicochemical properties of PEVs and their bioactivities and mechanisms in mediating microbiota-host communication, and elucidate the limitations of the current research on PEVs and their potential application as postbiotics.
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Affiliation(s)
- Xiaoming Zhang
- College of Basic Medical Science, Dalian Medical University, Dalian, China
| | - Ye Wang
- College of Basic Medical Science, Dalian Medical University, Dalian, China
| | - Qiyu E
- College of Basic Medical Science, Dalian Medical University, Dalian, China
| | - Muhammad Naveed
- College of Basic Medical Science, Dalian Medical University, Dalian, China
| | - Xiuli Wang
- College of Basic Medical Science, Dalian Medical University, Dalian, China
| | - Yinhui Liu
- College of Basic Medical Science, Dalian Medical University, Dalian, China
| | - Ming Li
- College of Basic Medical Science, Dalian Medical University, Dalian, China.
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18
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Gu X, Fan Z, Lu L, Xu H, He L, Shen H, Huang R, Li Z. Machine learning-assisted washing-free detection of extracellular vesicles by target recycling amplification based fluorescent aptasensor for accurate diagnosis of gastric cancer. Talanta 2025; 287:127506. [PMID: 39837204 DOI: 10.1016/j.talanta.2024.127506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Revised: 12/07/2024] [Accepted: 12/30/2024] [Indexed: 01/23/2025]
Abstract
Extracellular vesicles (EVs) are promising non-invasive biomarkers for cancer diagnosis. EVs proteins play a critical role in tumor progress and metastasis. However, accurately and reliably diagnosing cancers is greatly limited by single protein marker on EVs. Here, we reported an accurate diagnosis model of gastric cancer by analyzing five types of EVs surface proteins using machine learning in a retrospective study design. A washing-free detection method based on aptasensor and exonuclease Ⅰ was used to profile EVs surface proteins. The aptamer was designed as hairpin structure. The presence of target protein positive EVs converted the conformation of hairpin probes, which subsequently degraded by exonuclease Ⅰ. The exposed target protein could bind with and then open new hairpin probes, thus forming an amplification cycle. The lengths of different detection probes were optimized for detection. With the combination of five target proteins, five machine learning algorithms were compared to achieve a higher diagnostic accuracy. The best model, XGBoost, validated with 20 % of detection results could reach an accuracy of 0.8421. Furthermore, the XGBoost-based surface protein analysis could precisely identify gastric cancer patients with the area under the curve value of 0.9347 (95 % confidential interval (CI) = 0.8590 to 1.000). Since our method utilized a simple and versatile design of detection probes, its diagnostic scope could potentially be expanded to include different protein markers and accurately diagnose other diseases in the future.
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Affiliation(s)
- Xinrui Gu
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, Jiangsu Province, 210008, China
| | - Zeyu Fan
- School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, Jiangsu Province, 211816, China
| | - Luying Lu
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, Jiangsu Province, 210008, China
| | - Hongpan Xu
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, Jiangsu Province, 210008, China
| | - Lei He
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, Jiangsu Province, 210008, China
| | - Han Shen
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, Jiangsu Province, 210008, China.
| | - Rongrong Huang
- School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, Jiangsu Province, 211816, China.
| | - Zhiyang Li
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, Jiangsu Province, 210008, China
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19
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Yi K, Zhang Z, Chen P, Xi X, Zhao X, Rong Y, Long F, Zhang Q, Zhang Y, Gao M, Liu W, Liu BF, Zhu Z, Wang F. Tidal microfluidic chip-based isolation and transcriptomic profiling of plasma extracellular vesicles for clinical monitoring of high-risk patients with hepatocellular carcinoma-associated precursors. Biosens Bioelectron 2025; 276:117228. [PMID: 39954520 DOI: 10.1016/j.bios.2025.117228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 12/02/2024] [Accepted: 02/02/2025] [Indexed: 02/17/2025]
Abstract
Hepatocellular carcinoma (HCC) poses a significant global health burden, with escalating incidence rates and substantial mortality. The predominant etiological factors include liver cirrhosis (LC) and chronic hepatitis B infections (CHB). Surveillance primarily relies on ultrasound and Alpha-fetoprotein (AFP), yet their efficacy, particularly in early HCC detection, is limited. Hence, there is a critical need for accurate non-invasive biomarkers to enhance surveillance and early diagnosis. Extracellular vesicles (EVs) hold promises as stable carriers of signaling molecules, offering potential in tumor diagnosis. Our study developed a novel tidal microfluidic chip for label-free EV isolation, enabling rapid and efficient enrichment from small plasma volumes. Through transcriptome sequencing and single-cell analysis, we identified HMMR and B4GALT2 as promising HCC-associated biomarkers in EVs. In a comprehensive clinical evaluation, bi-mRNAs in EVs exhibited superior diagnostic performance over AFP, particularly in distinguishing early-stage HCC or AFP-negative cases from high-risk individuals (CHB/LC). Notably, our study demonstrated the potential of bi-mRNAs to complement imaging examinations, enabling early detection of HCC lesions. In conclusion, the tidal microfluidic chip offers a practical solution for EV isolation, with the integration of EV-based biomarkers presenting opportunities for improved early detection and management of HCC in clinical practice.
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Affiliation(s)
- Kezhen Yi
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, No.169 Donghu Road, Wuchang District, Wuhan, 430071, PR China
| | - Zhonglin Zhang
- Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, PR China
| | - Peng Chen
- The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, PR China
| | - Xiaodan Xi
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, No.169 Donghu Road, Wuchang District, Wuhan, 430071, PR China
| | - Xudong Zhao
- The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, PR China
| | - Yuan Rong
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, No.169 Donghu Road, Wuchang District, Wuhan, 430071, PR China
| | - Fei Long
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, No.169 Donghu Road, Wuchang District, Wuhan, 430071, PR China
| | - Qian Zhang
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, No.169 Donghu Road, Wuchang District, Wuhan, 430071, PR China
| | - Ying Zhang
- Department of General Surgery, The 5th Center of Chinese PLA General Hospital, Beijing, PR China
| | - Menglu Gao
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, No.169 Donghu Road, Wuchang District, Wuhan, 430071, PR China
| | - Weihuang Liu
- Medical Research Center for Structural Biology, School of Basic Medical Sciences, Wuhan University, PR China
| | - Bi-Feng Liu
- The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, PR China.
| | - Zhenyu Zhu
- Department of Hepatobiliary Surgery, Senior Department of Hepatology, The Fifth Medical Center of PLA Central Hospital, Beijing, PR China.
| | - Fubing Wang
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, No.169 Donghu Road, Wuchang District, Wuhan, 430071, PR China; Center for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University, Wuhan, PR China; Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan, PR China.
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20
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Sonar S, Das A, Yeong Zher L, Narayanan Ravi R, Zheng Kong EQ, Dhar R, Narayanan K, Gorai S, Subramaniyan V. Exosome-Based Sensor: A Landmark of the Precision Cancer Diagnostic Era. ACS APPLIED BIO MATERIALS 2025. [PMID: 40366154 DOI: 10.1021/acsabm.5c00288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/15/2025]
Abstract
Extracellular vesicles are nanoscale vesicles released by a diversity of cells that mediate intercellular communication by transporting an array of biomolecules. They are gaining increasing attention in cancer research due to their ability to carry specific biomarkers. This characteristic makes them potentially useful for highly sensitive, noninvasive diagnostic procedures and more precise prognostic assessments. Consequently, EVs are emerging as a transformative tool in cancer treatment, facilitating early detection and personalized medicine. Despite significant progress, clinical implementation is hindered by challenges in EV isolation, purification, and characterization. However, developing advanced biosensor technologies offers promising solutions to these obstacles. This review highlights recent progress in biosensors for EV detection and analysis, focusing on various sensing modalities including optical, electrochemical, microfluidic, nanomechanical, and biological sensors. We also explore techniques for EV isolation, characterization, and analysis, such as electron microscopy, atomic force microscopy, nanoparticle tracking analysis, and single-particle analysis. Furthermore, the review critically assesses the challenges associated with EV detection and put forward future directions, aiming to usher in a cutting-edge era of precision medicine through advanced, sensor-based, noninvasive early cancer diagnosis by detecting EV-carried biomarkers.
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Affiliation(s)
- Swarup Sonar
- Department of Oncology, Neuron Institute of Applied Research, Amravati, Maharashtra 444605, India
| | - Asmit Das
- Department of Oncology, Neuron Institute of Applied Research, Amravati, Maharashtra 444605, India
| | - Lee Yeong Zher
- Monash University Malaysia, Bandar Sunway, Subang Jaya 47500, Selangor, Malaysia
| | - Ram Narayanan Ravi
- Monash University Malaysia, Bandar Sunway, Subang Jaya 47500, Selangor, Malaysia
| | - Eason Qi Zheng Kong
- Monash University Malaysia, Bandar Sunway, Subang Jaya 47500, Selangor, Malaysia
| | - Rajib Dhar
- Division of Pharmacology, Faculty of Medical and Life Sciences, Sunway University, Bandar Sunway, Subang Jaya 47500, Selangor (Darul Ehsan), Malaysia
| | - Kumaran Narayanan
- Monash University Malaysia, Bandar Sunway, Subang Jaya 47500, Selangor, Malaysia
| | - Sukhamoy Gorai
- Department of Neurological Sciences, Rush University Medical Center, 1620 W Harrison Street, Chicago, Illinois 60612, United States
| | - Vetriselvan Subramaniyan
- Division of Pharmacology, Faculty of Medical and Life Sciences, Sunway University, Bandar Sunway, Subang Jaya 47500, Selangor (Darul Ehsan), Malaysia
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21
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Zhou H, Li D, Lv Q, Lee C. Integrative plasmonics: optical multi-effects and acousto-electric-thermal fusion for biosensing, energy conversion, and photonic circuits. Chem Soc Rev 2025. [PMID: 40354162 DOI: 10.1039/d4cs00427b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/14/2025]
Abstract
Surface plasmons, a unique optical phenomenon arising at the interface between metals and dielectrics, have garnered significant interest across fields such as biochemistry, materials science, energy, optics, and nanotechnology. Recently, plasmonics is evolving from a focus on "classical plasmonics," which emphasizes fundamental effects and applications, to "integrative plasmonics," which explores the integration of plasmonics with multidisciplinary technologies. This review explores this evolution, summarizing key developments in this technological shift and offering a timely discussion on the fusion mechanisms, strategies, and applications. First, we examine the integration mechanisms of plasmons within the realm of optics, detailing how fundamental plasmonic effects give rise to optical multi-effects, such as plasmon-phonon coupling, nonlinear optical effects, electromagnetically induced transparency, chirality, nanocavity resonance, and waveguides. Next, we highlight strategies for integrating plasmons with technologies beyond optics, analyzing the processes and benefits of combining plasmonics with acoustics, electronics, and thermonics, including comprehensive plasmonic-electric-acousto-thermal integration. We then review cutting-edge applications in biochemistry (molecular diagnostics), energy (harvesting and catalysis), and informatics (photonic integrated circuits). These applications involve surface-enhanced Raman scattering (SERS), surface-enhanced infrared absorption (SEIRA), surface-enhanced fluorescence (SEF), chirality, nanotweezers, photoacoustic imaging, perovskite solar cells, photocatalysis, photothermal therapy, and triboelectric nanogenerators (TENGs). Finally, we conclude with a forward-looking perspective on the challenges and future of integrative plasmonics, considering advances in mechanisms (quantum effects, spintronics, and topology), materials (Dirac semimetals and hydrogels), technologies (machine learning, edge computing, in-sensor computing, and neuroengineering), and emerging applications (5G, 6G, virtual reality, and point-of-care testing).
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Affiliation(s)
- Hong Zhou
- Department of Electrical and Computer Engineering, National University of Singapore, Singapore 117583, Singapore.
- Center for Intelligent Sensors and MEMS (CISM), National University of Singapore, Singapore 117583, Singapore
- NUS Graduate School-Integrative Sciences and Engineering Programme (ISEP), National University of Singapore, Singapore 119077, Singapore
- School of Mechanical Engineering, Northwestern Polytechnical University, Xi'an 710072, China
| | - Dongxiao Li
- Department of Electrical and Computer Engineering, National University of Singapore, Singapore 117583, Singapore.
- Center for Intelligent Sensors and MEMS (CISM), National University of Singapore, Singapore 117583, Singapore
| | - Qiaoya Lv
- Department of Electrical and Computer Engineering, National University of Singapore, Singapore 117583, Singapore.
- Center for Intelligent Sensors and MEMS (CISM), National University of Singapore, Singapore 117583, Singapore
| | - Chengkuo Lee
- Department of Electrical and Computer Engineering, National University of Singapore, Singapore 117583, Singapore.
- Center for Intelligent Sensors and MEMS (CISM), National University of Singapore, Singapore 117583, Singapore
- NUS Graduate School-Integrative Sciences and Engineering Programme (ISEP), National University of Singapore, Singapore 119077, Singapore
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22
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Ma H, Li J, Gao M, Dong Y, Luo Y, Su S. An Electrochemical Aptasensor for Accurate and Sensitive Detection of Exosomes Based on Dual-Probe Recognition and Hybridization Chain Reaction. BIOSENSORS 2025; 15:302. [PMID: 40422041 DOI: 10.3390/bios15050302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/09/2025] [Revised: 04/30/2025] [Accepted: 05/07/2025] [Indexed: 05/28/2025]
Abstract
The accurate and sensitive detection of tumor-derived exosomes holds significant promise for the early diagnosis of cancer. In this study, an electrochemical aptasensor was developed for the high-performance detection of exosomes by integrating dual-probe recognition and hybridization chain reaction (HCR). A dual-probe recognition unit composed of a MUC1 aptamer (MUC1-Apt) probe and cholesterol probe was designed for capturing target exosomes and reducing the interference from free proteins, significantly improving the accuracy of exosome detection. It should be noted that the dual-probe recognition unit was formed in conjunction with the HCR. Moreover, a large number of biotins were also assembled on the HCR product, which were used to capture avidin-horseradish peroxidase (SA-HRP) for signal amplification. The CD63 aptamer (CD63-Apt) was immobilized on the surface of a gold electrode for specifically capturing exosomes to construct a classical sandwiched structure. The loaded SA-HRP can efficiently catalyze the reaction of 3, 3', 5, 5' tetramethylbenzidine (TMB) and hydrogen peroxide (H2O2) to generate a large electrochemical signal. According to this phenomenon, a linear relationship of this proposed aptasensor was achieved between the electrochemical response and 1 × 102-1 × 107 particles/mL exosomes, with a detection limit of 45 particles/mL. Moreover, the aptasensor exhibited accepted stability and potential clinical applicability. All results proved that this aptasensor has a promising application in exosome-based disease diagnostics.
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Affiliation(s)
- Haojie Ma
- State Key Laboratory of Flexible Electronics (LoFE) & Jiangsu Key Laboratory of Smart Biomaterials and Theranostic Technology, Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, 9 Wenyuan Road, Nanjing 210023, China
| | - Jie Li
- State Key Laboratory of Flexible Electronics (LoFE) & Jiangsu Key Laboratory of Smart Biomaterials and Theranostic Technology, Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, 9 Wenyuan Road, Nanjing 210023, China
| | - Mengjia Gao
- State Key Laboratory of Flexible Electronics (LoFE) & Jiangsu Key Laboratory of Smart Biomaterials and Theranostic Technology, Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, 9 Wenyuan Road, Nanjing 210023, China
| | - Yan Dong
- State Key Laboratory of Flexible Electronics (LoFE) & Jiangsu Key Laboratory of Smart Biomaterials and Theranostic Technology, Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, 9 Wenyuan Road, Nanjing 210023, China
| | - Yi Luo
- State Key Laboratory of Flexible Electronics (LoFE) & Jiangsu Key Laboratory of Smart Biomaterials and Theranostic Technology, Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, 9 Wenyuan Road, Nanjing 210023, China
| | - Shao Su
- State Key Laboratory of Flexible Electronics (LoFE) & Jiangsu Key Laboratory of Smart Biomaterials and Theranostic Technology, Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, 9 Wenyuan Road, Nanjing 210023, China
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Wang CY, Wang M, Zhao CY, Zhou Q, Zhang XY, Wang FX, Dong JM, Du CP, Zhang CL, Dang Y, Yang AJ, Dong JF, Li M. ADAMTS-13 Prevents VWF-Mediated Gastric Cancer Metastasis. Arterioscler Thromb Vasc Biol 2025. [PMID: 40336476 DOI: 10.1161/atvbaha.125.322553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Accepted: 04/17/2025] [Indexed: 05/09/2025]
Abstract
BACKGROUND Gastric cancer invades local tissue extensively and metastasizes through the circulation to remote organs. Patients with metastasized gastric cancer have poor clinical outcomes. The vasculature in the cancer niche is developed poorly, thus allowing cancer cells to be released into the circulation. However, it is poorly understood how cancer cells adhere to and transmigrate through the fully developed endothelium in remote organs and what key adhesive ligands are involved in the process. Here, we report results from a study designed to investigate the role of hyperadhesive VWF (von Willebrand factor) in promoting the pulmonary metastasis of gastric cancer. METHODS We used mouse models to investigate the roles of hyperadhesive VWF in the pulmonary metastasis of gastric cancer. The findings from these mouse models were validated through in vitro experiments that specifically examined how VWF promoted gastric cancer-derived extracellular vesicles to activate endothelial cells and analyzed established databases of patients with gastric cancer. RESULTS VWF in cancer-bearing mice became hyperadhesive and mediated the adhesion of gastric cancer-derived extracellular vesicles to the endothelium, where gastric cancer-derived extracellular vesicles caused endothelial permeability and promoted the transmigration of cancer cells to the interstitial tissue of the lungs. Reducing VWF adhesive activity by the metalloprotease ADAMTS-13 (A disintegrin and metalloprotease with thrombospondin type motifs, type 13) prevented the pulmonary metastasis of gastric cancer cells in mice. We further validated the findings in mice through targeted in vitro experiments and by associating VWF with the outcomes of patients with gastric cancer through established databases of patients with gastric cancer using bioinformatics tools. CONCLUSIONS We show how VWF becomes hyperadhesive to promote the pulmonary metastasis of gastric cancer through its interaction with gastric cancer-derived extracellular vesicles and that the hyperadhesive activity of VWF is reduced by ADAMTS-13 to prevent the metastasis.
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Affiliation(s)
- Chen-Yu Wang
- Institute of Pathology, School of Basic Medical Sciences, Lanzhou University, China. (C.-y.W., M.W., C.-y.Z., Q.Z., X.-y.Z., J.-m.D., C.-p.D., C.-l.Z., Y.D., A.-j.Y., M.L.)
| | - Min Wang
- Institute of Pathology, School of Basic Medical Sciences, Lanzhou University, China. (C.-y.W., M.W., C.-y.Z., Q.Z., X.-y.Z., J.-m.D., C.-p.D., C.-l.Z., Y.D., A.-j.Y., M.L.)
- Experimental Teaching Center of Basic Medicine, School of Basic Medical Science, Lanzhou University, China. (M.W.)
| | - Chan-Yuan Zhao
- Institute of Pathology, School of Basic Medical Sciences, Lanzhou University, China. (C.-y.W., M.W., C.-y.Z., Q.Z., X.-y.Z., J.-m.D., C.-p.D., C.-l.Z., Y.D., A.-j.Y., M.L.)
| | - Quan Zhou
- Institute of Pathology, School of Basic Medical Sciences, Lanzhou University, China. (C.-y.W., M.W., C.-y.Z., Q.Z., X.-y.Z., J.-m.D., C.-p.D., C.-l.Z., Y.D., A.-j.Y., M.L.)
| | - Xiao-Yu Zhang
- Institute of Pathology, School of Basic Medical Sciences, Lanzhou University, China. (C.-y.W., M.W., C.-y.Z., Q.Z., X.-y.Z., J.-m.D., C.-p.D., C.-l.Z., Y.D., A.-j.Y., M.L.)
| | | | - Jia-Ming Dong
- Institute of Pathology, School of Basic Medical Sciences, Lanzhou University, China. (C.-y.W., M.W., C.-y.Z., Q.Z., X.-y.Z., J.-m.D., C.-p.D., C.-l.Z., Y.D., A.-j.Y., M.L.)
| | - Cun-Pu Du
- Institute of Pathology, School of Basic Medical Sciences, Lanzhou University, China. (C.-y.W., M.W., C.-y.Z., Q.Z., X.-y.Z., J.-m.D., C.-p.D., C.-l.Z., Y.D., A.-j.Y., M.L.)
| | - Chen-Li Zhang
- Institute of Pathology, School of Basic Medical Sciences, Lanzhou University, China. (C.-y.W., M.W., C.-y.Z., Q.Z., X.-y.Z., J.-m.D., C.-p.D., C.-l.Z., Y.D., A.-j.Y., M.L.)
| | - Yun Dang
- Institute of Pathology, School of Basic Medical Sciences, Lanzhou University, China. (C.-y.W., M.W., C.-y.Z., Q.Z., X.-y.Z., J.-m.D., C.-p.D., C.-l.Z., Y.D., A.-j.Y., M.L.)
- Gansu Provincial Maternity and Child-Care Hospital, Lanzhou, China (Y.D.)
| | - Ai-Jun Yang
- Institute of Pathology, School of Basic Medical Sciences, Lanzhou University, China. (C.-y.W., M.W., C.-y.Z., Q.Z., X.-y.Z., J.-m.D., C.-p.D., C.-l.Z., Y.D., A.-j.Y., M.L.)
| | - Jing-Fei Dong
- Bloodworks Research Institute, Seattle, WA (J.-f.D.)
- Division of Hematology, Department of Medicine, University of Washington School of Medicine, Seattle (J.-f.D.)
| | - Min Li
- Institute of Pathology, School of Basic Medical Sciences, Lanzhou University, China. (C.-y.W., M.W., C.-y.Z., Q.Z., X.-y.Z., J.-m.D., C.-p.D., C.-l.Z., Y.D., A.-j.Y., M.L.)
- Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, China. (M.L.)
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24
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Liu S, Feng A, Li Z. Neuron-Derived Extracellular Vesicles: Emerging Regulators in Central Nervous System Disease Progression. Mol Neurobiol 2025:10.1007/s12035-025-05010-4. [PMID: 40325332 DOI: 10.1007/s12035-025-05010-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2025] [Accepted: 04/29/2025] [Indexed: 05/07/2025]
Abstract
The diagnosis and exploration of central nervous system (CNS) diseases remain challenging due to the blood-brain barrier (BBB), complex signaling pathways, and heterogeneous clinical manifestations. Neurons, as the core functional units of the CNS, play a pivotal role in CNS disease progression. Extracellular vesicles (EVs), capable of crossing the BBB, facilitate intercellular and cell-extracellular matrix (ECM) communication, making neuron-derived extracellular vesicles (NDEVs) a focal point of research. Recent studies reveal that NDEVs, carrying various bioactive substances, can exert either pathogenic or protective effects in numerous CNS diseases. Additionally, NDEVs show significant potential as biomarkers for CNS diseases. This review summarizes the emerging roles of NDEVs in CNS diseases, including Alzheimer's disease, depression, traumatic brain injury, schizophrenia, ischemic stroke, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. It aims to provide a novel perspective on developing therapeutic and diagnostic strategies for CNS diseases through the study of NDEVs.
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Affiliation(s)
- Sitong Liu
- Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518107, China
- School of Medicine, Sun Yat-Sen University, Shenzhen, 518107, China
| | - Aitong Feng
- Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518107, China
- School of Medicine, Sun Yat-Sen University, Shenzhen, 518107, China
| | - Zhigang Li
- Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518107, China.
- Shenzhen Key Laboratory of Chinese Medicine Active Substance Screening and Translational Research, Shenzhen, 518107, China.
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25
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XING Y, REN X, LI D, LIU L. [Exosome separation and analysis based on microfluidics technology and its clinical applications]. Se Pu 2025; 43:455-471. [PMID: 40331610 PMCID: PMC12059995 DOI: 10.3724/sp.j.1123.2024.10032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Indexed: 05/08/2025] Open
Abstract
Exosomes are cell-secreted nanoscale vesicles 30-150 nm in size and encompass a diverse array of biomolecules, including lipids, proteins, and nucleic acids. Exosomes play pivotal roles during the intercellular exchange of materials and information, and are closely associated with the onset and progression of a variety of diseases. Therefore, comprehensively investigating exosomes is very important in terms of disease diagnosis and treatment. However, exosomes are genetically heterogeneous and are composed of different materials. Additionally, exosome-size and packing-specific-biomarker heterogeneities result in biofunction diversity. Moreover, isolating and analyzing exosomes is highly challenging owing to their small sizes and heterogeneities. Accordingly, effective separation methods and analytical techniques for highly specifically and efficiently identifying exosomes are urgently needed in order to better understand their functionalities. While separation and analysis is required to reveal exosome heterogeneity, the former is confronted by three primary challenges. Firstly, exosome heterogeneity (including heterogeneous marker expressions and size heterogeneity that results in heterogeneous functions) results in systems that are very difficult to separate. Secondly, the coexistence of non-vesicular contaminants (lipoprotein nanoparticles, soluble proteins, nucleic acids, etc.) and the complex matrix effects of body fluids also contribute to separation difficulties. Thirdly, enrichment is a highly challenging task owing to low exosome concentrations. Traditional methods, such as ultracentrifugation and size-exclusion chromatography, fall short in terms of their abilities to precisely separate and analyze exosomes. On the other hand, microfluidics has emerged as a robust tool for the efficient analysis of complex biological samples and is characterized by miniaturization, precise control, high throughput, automation, and integration. Firstly, the operability, integrability, and modifiability of a microfluidics system facilitate exosome separation and purification based on surface properties, size, charge, and polarity. Secondly, the use of a microfluidics approach, with its high throughput, low reagent consumption, and multichannel manipulability, greatly facilitates preparing exosomes and enhancing their concentrations. Thirdly, microfluidics ensures that diverse separation methods are compatible with downstream analysis techniques. Exosomes are highly heterogeneous; hence, they are classified by type and subpopulation (according to origin, size, molecular markers, functions, etc.). This paper first discusses microfluidics techniques for separating exosomes and examines various separation strategies grounded in the physicochemical properties of exosomes. We then analyze exosome detection methodologies that use microfluidics platforms and encompass traditional group-exosome analysis techniques and novel single-exosome analysis approaches. Finally, we discuss future clinical applications of microfluidics technology in exosome research, particularly its potential for diagnosing and treating diseases, thereby underscoring the applications value of microfluidics technology in the realm of personalized and precision medicine. Furthermore, cutting-edge microfluidics platforms offer novel perspectives for purifying and preparing EVs owing to precise fluid control, integration, miniaturization, and high-throughput characterization. EV populations, subpopulations, and single vesicles can be purified based on their physicochemical properties and microfluidics features. Comprehensive lab-on-a-chip methods are promising in terms of separating EVs based on traits, such as size, surface markers, and charge, and for obtaining highly pure EVs. Recycled EV samples can be prepared by controlling the high-throughput and multichannel capabilities of microfluidics approaches. The transition from bulk EV analysis to single-vesicle analysis provides opportunities to explore the heterogeneous nature of EVs, thereby augmenting their potential for disease diagnosis.
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26
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Allemailem KS, Rahmani AH, almansour NM, Aldakheel FM, Albalawi GM, Albalawi GM, Khan AA. Current updates on the structural and functional aspects of the CRISPR/Cas13 system for RNA targeting and editing: A next‑generation tool for cancer management (Review). Int J Oncol 2025; 66:42. [PMID: 40342053 PMCID: PMC12068846 DOI: 10.3892/ijo.2025.5748] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Accepted: 04/02/2025] [Indexed: 05/11/2025] Open
Abstract
For centuries, a competitive evolutionary race between prokaryotes and related phages or other mobile genetic elements has led to the diversification of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR‑associated sequence (Cas) genome‑editing systems. Among the different CRISPR/Cas systems, the CRISPR/Cas9 system has been widely studied for its precise DNA manipulation; however, due to certain limitations of direct DNA targeting, off‑target effects and delivery challenges, researchers are looking to perform transient knockdown of gene expression by targeting RNA. In this context, the more recently discovered type VI CRISPR/Cas13 system, a programmable single‑subunit RNA‑guided endonuclease system that has the capacity to target and edit any RNA sequence of interest, has emerged as a powerful platform to modulate gene expression outcomes. All the Cas13 effectors known so far possess two distinct ribonuclease activities. Pre‑CRISPR RNA processing is performed by one RNase activity, whereas the two higher eukaryotes and prokaryotes nucleotide‑binding domains provide the other RNase activity required for target RNA degradation. Recent innovative applications of the type VI CRISPR/Cas13 system in nucleic acid detection, viral interference, transcriptome engineering and RNA imaging hold great promise for disease management. This genome editing system can also be employed by the Specific High Sensitivity Enzymatic Reporter Unlocking platform to identify any tumor DNA. The discovery of this system has added a new dimension to targeting, tracking and editing circulating microRNA/RNA/DNA/cancer proteins for the management of cancer. However, there is still a lack of thorough understanding of the mechanisms underlying some of their functions. The present review summarizes the recent updates on the type VI CRISPR/Cas system in terms of its structural and mechanistic properties and some novel applications of this genome‑editing tool in cancer management. However, some issues, such as collateral degradation of bystander RNA, impose major limitations on its in vivo application. Furthermore, additional challenges and future prospects for this genome editing system are described in the present review.
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Affiliation(s)
- Khaled s. Allemailem
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia
| | - Arshad Husain Rahmani
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia
| | - Nahlah Makki almansour
- Department of Biology, College of Science, University of Hafr Al Batin, Hafr Al Batin 31991, Saudi Arabia
| | - Fahad M. Aldakheel
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia
| | - Ghadah Mohammad Albalawi
- Department of Laboratory and Blood Bank, King Fahd Specialist Hospital, Tabuk 47717, Saudi Arabia
| | | | - Amjad Ali Khan
- Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia
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27
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Huang Q, Wang J, Ning H, Liu W, Han X. Exosome isolation based on polyethylene glycol (PEG): a review. Mol Cell Biochem 2025; 480:2847-2861. [PMID: 39702782 DOI: 10.1007/s11010-024-05191-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Accepted: 12/07/2024] [Indexed: 12/21/2024]
Abstract
Exosome acts as an outstanding biomarker for ongoing studies, diagnosis and prognosis of multiples diseases. Therefore, the call for economically and efficiently isolating a large number of exosomes is an active area of investigation. However, to date, the challenges including complex isolated procedure, uneconomical equipment, low protein content and distinct loss in the particle number of exosomes etc. still encounter in exosome isolation. Polyethylene glycol (PEG)-induced exosome isolation increasingly attracts wide attention of scientists. PEG precipitation reveals higher performance in the yield of exosomes among multiple common isolation techniques. PEG-based precipitation is a temporarily low-purity, but inexpensive, time-save, labor-less, convenient and high-yield technique to gain exosomes with high biological activities. Hence, the PEG-based exosome isolation approach wins the endorsement of experimental workers. Herein, we summary the existing knowledge on procedures of PEG-based exosomes separation from different biospecimens, the binding process of PEG to exosomes, some notices, demerits, merits of PEG-based exosome isolation, and at last the advantages by combining PEG-precipitation to other techniques for exosome isolation, with a view to eliciting profound insights for investigators who recruit PEG for exosome separation, and advancing references for the standardization of PEG-based exosome isolation in future.
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Affiliation(s)
- Qionglian Huang
- Institute of Chinese Traditional Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jue Wang
- Institute of Chinese Traditional Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Hanjuan Ning
- Institute of Chinese Traditional Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Weiwei Liu
- Institute of Chinese Traditional Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xianghui Han
- Institute of Chinese Traditional Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
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28
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HUANG Y, WANG H, ZHANG Y, LIN Y, QIAO X, HU L. [Bibliometric analysis of exosomes in the biomarker research field]. Se Pu 2025; 43:498-507. [PMID: 40331613 PMCID: PMC12059985 DOI: 10.3724/sp.j.1123.2025.01025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2025] [Indexed: 05/08/2025] Open
Abstract
Exosomes are extracellular vesicles secreted by cells and are rich in genetic material and proteins. The surfaces of exosome membranes contain many blast-specific markers that provide an important basis for disease diagnosis, progression, and treatment. Herein, we searched the Web of Science core collection (SCI-EXPENED) database for research and review articles on "exosomes" and "biomarkers" or "diagnostics" or "liquid biopsy" as research topics between 2010 and 2024. Bibliometric analysis revealed that exosomes have received increasing levels of attention as disease biomarkers, with China contributing the most to these studies. Herein, we focus on marker diagnoses for cancer, inflammation, and diabetes, as well as neurodegenerative and cardiovascular diseases. Chromatography, mass spectrometry, Raman spectroscopy, and other techniques are typically used to analyze exosomal nucleic acids, proteins, and metabolites, with commonly used test samples including plasma, serum, urine, saliva, cerebrospinal fluid, and other bodily fluids. Research into exosomes as tumor markers has mainly focused on eight highly prevalent cancers, including lung, breast, and prostate cancers. This paper focuses on exosomes as disease biomarkers and uses a bibliometric tool system to analyze the use of exosomes and their contents as biomarkers in the disease diagnosis field between 2010 and 2024, analyzes development prospects, and discusses future exosome-mediated efforts for diagnosing and treating diseases, and is expected to provide a reference for studying and applying exosomes as disease markers.
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29
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XU K, HUANG Y, ZHAO R. [Research progress of peptide recognition-guided strategies for exosome isolation and enrichment]. Se Pu 2025; 43:446-454. [PMID: 40331609 PMCID: PMC12059989 DOI: 10.3724/sp.j.1123.2024.10015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Indexed: 05/08/2025] Open
Abstract
Exosomes are bilayered vesicles derived from living cells and bacteria that are loaded with abundant biomolecules, such as proteins and nucleic acids. As an important medium of remote cell communication, exosomes are closely related to the occurrence and development of a number of diseases, including those involving tumors and inflammation. The isolation and enrichment of exosomes in complex biosystems is greatly significant for the diagnosis, prognosis, and detection of diseases, as well as in molecular-mechanism research. However, exosomes are usually nanoscale size distribution and widely existed in complex biological samples, including blood, tissue fluids, and urine, which bring difficulties and challenges to the isolation and enrichment of exosomes. To address this issue, several methods based on the physical properties of exosomes have been developed. For example, exosomes can be obtained by ultracentrifugation at high centrifugal force based on density differences; they can also be isolated and enriched by size-exclusion chromatography and ultrafiltration based on size heterogeneity. Exosomes can also be separated in high yields but with low purities using commercial polymer-coprecipitation-based isolation kits. While the abovementioned methods can be used to isolate and enrich exosomes in a highly efficient manner, accurately distinguishing interfering particles, including protein aggregates and microvesicles, in biosystems is still difficult, resulting in the poor purity of exosome isolation and enrichment. Affinity ligands are widely used during the affinity isolation and enrichment of exosomes. Antibodies exhibit high selectivity and affinity; consequently exosomes can be captured highly selectively by exploiting specific antigen/antibody interactions. However, antibodies also have some limitations, including complex preparation procedures, high costs, and poor stability. Chemical affinity ligands, such as aptamers, peptides, and small molecules, are also widely used to isolate and enrich exosomes. As a kind of molecular recognition tool, peptides contain a variety of amino acids and exhibit many advantages, including good biocompatibility, low immunogenicity, and design flexibility. Solid-phase synthesis strategies have rapidly developed, thereby providing a basis for automated and large-scale peptide synthesis. Affinity peptides have been widely used to recognize and analyze target biomolecules in complex physiological environments in a highly selective manner. A series of protein-targeting peptides has been reported based on the biomolecular characteristics of exosomes. These affinity peptides can be specifically anchored onto highly enriched transmembrane proteins on exosome surfaces, thereby enabling the efficient and highly selective isolation and enrichment of exosomes in complex systems. Additionally, exosomes contain stable bilayer membranes consisting of abundant and diverse phospholipid molecules. The development of phospholipid-molecule-targeting peptides is expected to effectively eliminate interference from protein aggregates and other particles. In addition to differences in the compositions of phospholipids in biofilms, exosomes are smaller and more curved than apoptotic bodies and microvesicles. A series of affinity peptides capable of inducing and sensing high membrane curvatures are widely used to isolate and enrich exosomes. The tumor microenvironment can produce and release tumor-derived exosomes that are buried in a large number of normal cell-derived exosomes. Accordingly, pH-responsive peptides have been designed and modified based on the acidic environments of tumor-derived exosomes, which were accurately and tightly anchored via peptide insertion and folding. Focusing on the current status of exosome research, this paper introduces and summarizes current and widely used methods for isolating and enriching exosomes. Various exosome-targeting peptide-design and screening principles are introduced based on the characteristics and advantages of peptides. The applications of these peptides to the isolation and enrichment of exosomes are also summarized, thereby providing strong guidance for the efficient and highly selective isolation and enrichment of exosomes in complex life-related systems.
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Rajendran RL, Gangadaran P, Ghosh S, Nagarajan AK, Batabyal R, Ahn BC. Unlocking the secrets of single extracellular vesicles by cutting-edge technologies. Pathol Res Pract 2025; 269:155878. [PMID: 40024075 DOI: 10.1016/j.prp.2025.155878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 02/20/2025] [Accepted: 02/27/2025] [Indexed: 03/04/2025]
Abstract
Extracellular vesicles (EVs), isolated through techniques such as liquid biopsy, have emerged as crucial biomarkers in various diseases, including cancer. EVs were dismissed initially as cellular debris, EVs are now recognized for their role in intercellular communication, carrying proteins, RNAs, and other molecules between cells. Their stability in biofluids and ability to mirror their parent cells' molecular composition make them attractive candidates for non-invasive diagnostics. EVs, including microvesicles and exosomes, contribute to immune modulation and cancer progression, presenting both therapeutic challenges and opportunities. However, despite advances in analytical techniques like high-resolution microscopy and nanoparticle tracking analysis (NTA), standardization in EV isolation and characterization remains a hurdle. Cutting-edge technologies, such as atomic force microscopy and Raman tweezers microspectroscopy, have enhanced our understanding of single EVs, yet issues like low throughput and high technical complexity limit their widespread application. Other technologies like transmission electron microscopy, cryogenic transmission electron microscopy, super-resolution microscopy, direct stochastic optical reconstruction microscopy, single-molecule localization microscopy, tunable resistive pulse sensing, single-particle interferometric reflectance imaging sensor, flow cytometry, droplet digital analysis, total internal reflection fluorescence also contribute to EV analysis. Future research must focus on improving detection methods, developing novel analytical platforms, and integrating artificial intelligence to enhance the specificity of EV characterization. The future of EV research holds promise for breakthroughs in precision medicine, with a collaborative effort needed to translate these advancements into clinical practice.
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Affiliation(s)
- Ramya Lakshmi Rajendran
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; Cardiovascular Research Institute, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Prakash Gangadaran
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; Cardiovascular Research Institute, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Subhrojyoti Ghosh
- Department of Biotechnology, Indian Institute of Technology, Madras, Chennai 600036, India
| | - ArulJothi Kandasamy Nagarajan
- Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu, Tamilnadu 603203, India
| | - Rijula Batabyal
- Department of Biotechnology, Heritage Institute of Technology, Kolkata 700 107, India
| | - Byeong-Cheol Ahn
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; Cardiovascular Research Institute, Kyungpook National University, Daegu 41944, Republic of Korea; Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu 41944, Republic of Korea.
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Das A, Sonar S, Dhar R, Subramaniyan V. Exosomes in melanoma: Future potential for clinical theranostics. Pathol Res Pract 2025; 269:155950. [PMID: 40179441 DOI: 10.1016/j.prp.2025.155950] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2025] [Revised: 03/13/2025] [Accepted: 03/26/2025] [Indexed: 04/05/2025]
Abstract
Melanoma, an aggressive form of skin cancer, presents significant therapeutic challenges due to its resistance to conventional treatments and propensity for metastasis. Exosomes, nanoscale vesicles secreted by a wide variety of cells, have emerged as promising tools for developing novel melanoma therapies. Exosome-based therapeutic approaches offer several advantages, including inherent biocompatibility, low immunogenicity, and the ability to cross biological barriers. This review explores the therapeutic potential of exosomes in melanoma treatment, focusing on their multifaceted roles in modulating tumor cell behavior, enhancing anti-tumor immune responses, and serving as targeted drug delivery vehicles. We discuss various strategies employed to engineer exosomes for enhanced therapeutic efficacy, including loading them with chemotherapeutic agents, small interfering RNAs (siRNAs), microRNAs (miRNAs), and immunomodulatory molecules. Additionally, we highlight the potential of exosomes derived from diverse sources to enhance anti-cancer effects. Furthermore, we address the challenges and future directions in translating exosome-based therapies from bench to bedside, emphasizing the need for standardized isolation and manufacturing protocols, as well as rigorous preclinical and clinical evaluations to unlock the full therapeutic potential of exosomes in the fight against melanoma.
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Affiliation(s)
- Asmit Das
- Department of Oncology and Maxillofacial Pathology, Neuron Institute of Applied Research, Amravati, Maharashtra, India
| | - Swarup Sonar
- Department of Oncology and Maxillofacial Pathology, Neuron Institute of Applied Research, Amravati, Maharashtra, India
| | - Rajib Dhar
- Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, Subang Jaya, Selangor 47500, Malaysia
| | - Vetriselvan Subramaniyan
- Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, Subang Jaya, Selangor 47500, Malaysia.
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Parmal S, Subbappa P, Nikam V, Tarwate Y, Barhate K, Wagh S, Gholap AD, Dua K, Singh SK, Parikh D, Shaikh M, Khan TK, Rajput A. Hyaluronic acid based approaches for wound healing: A comprehensive review. Int J Biol Macromol 2025; 306:141625. [PMID: 40049471 DOI: 10.1016/j.ijbiomac.2025.141625] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Revised: 02/19/2025] [Accepted: 02/27/2025] [Indexed: 05/11/2025]
Abstract
Wound healing is a natural, however complex, tissue repair and regeneration mechanism. Understanding the cascade of biological events associated with wound healing facilitates scientists in designing topical skin formulations with enhanced therapeutic outcomes. In recent years, several innovative approaches have been utilized to treat wounds. Hyaluronic acid (HA)-based formulations have shown promising results. The current manuscript provides a systematic review of various aspects of HA, including its structure, synthesis, mechanism involved in wound healing, and various formulations developed using HA to treat wounds. Covered are innovative treatment strategies explicitly emphasizing nanocarrier-based approaches. Various patents wherein HA has been used to treat wounds are also summarized with the help of a Google patent search. Diving deep, clinical perspectives, toxicity aspects, and application of computational chemistry in HA research are also discussed.
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Affiliation(s)
- Samay Parmal
- Department of Pharmaceutics, Bharti Vidyapeeth Deemed to be University, Poona College of Pharmacy, Erandwane, Pune 411038, Maharashtra, India
| | - Praveen Subbappa
- Alliance Management and Supply Chain, Azurity Pharmaceuticals, Inc., 8 Cabot Road, Suite 2000, Woburn, MA 01801, USA
| | - Vaidehi Nikam
- Department of Pharmaceutics, Bharti Vidyapeeth Deemed to be University, Poona College of Pharmacy, Erandwane, Pune 411038, Maharashtra, India
| | - Yash Tarwate
- Department of Pharmaceutics, Bharti Vidyapeeth Deemed to be University, Poona College of Pharmacy, Erandwane, Pune 411038, Maharashtra, India
| | - Kunika Barhate
- Department of Pharmaceutics, Bharti Vidyapeeth Deemed to be University, Poona College of Pharmacy, Erandwane, Pune 411038, Maharashtra, India
| | - Shrutika Wagh
- Department of Pharmaceutics, Bharti Vidyapeeth Deemed to be University, Poona College of Pharmacy, Erandwane, Pune 411038, Maharashtra, India
| | - Amol D Gholap
- Department of Pharmaceutics, St. John Institute of Pharmacy and Research, Palghar 401404, Maharashtra, India; Department of Pharmaceutics, Amrutvahini College of Pharmacy, Sangamner 422608, Maharashtra, India
| | - Kamal Dua
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia; Faculty of Health, Australian Research Centre in Complementary & Integrative Medicine, University of Technology Sydney, Ultimo 2007, Australia
| | - Sachin Kumar Singh
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India; School of Medical and Life Sciences, Sunway University, 47500 Sunway City, Malaysia
| | - Dhaivat Parikh
- Department of Pharmaceutics, Institute of Pharmacy, Nirma University, S.G. Highway, Ahmedabad 382481, Gujarat, India
| | - Mushtaque Shaikh
- Department of Pharmaceutical Chemistry, Vivekanand Education Society's College of Pharmacy, Chembur (East), Mumbai 400074, Maharashtra, India
| | - Tamanna K Khan
- Department of Chemistry, Guru Nanak Khalsa College of Art Science and Commerce (Autonomus), Matunga (East), Mumbai 400019, Maharashtra, India
| | - Amarjitsing Rajput
- Department of Pharmaceutics, Bharti Vidyapeeth Deemed to be University, Poona College of Pharmacy, Erandwane, Pune 411038, Maharashtra, India.
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Li D, Li S, He S, He H, Yuan G, Ma B, Zhang Y, Yuan C, Liu Z, Deng Z, Xu J. Restoring tendon microenvironment in tendinopathy: Macrophage modulation and tendon regeneration with injectable tendon hydrogel and tendon-derived stem cells exosomes. Bioact Mater 2025; 47:152-169. [PMID: 39906648 PMCID: PMC11791013 DOI: 10.1016/j.bioactmat.2025.01.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Revised: 12/23/2024] [Accepted: 01/14/2025] [Indexed: 02/06/2025] Open
Abstract
Tendinopathy is a common musculoskeletal disorder in which a significant number of patients do not attain effective therapeutic outcomes. The extent of the inflammatory response and the dynamics of collagen synthesis metabolism are critical factors that influence the intrinsic self-repair capacity of tendons. However, the poor microenvironment within the tendon significantly impedes the self-repair process in tendinopathy. In this study, an injectable tendon-derived decellularized extracellular matrix (tdECM) hydrogel was utilized to treat tendinopathy. This hydrogel provides a more cytocompatible microenvironment while retaining certain bioactive factors of native tendon extracellular matrix (ECM), compared to collagen hydrogel. Notably, it was discovered for the first time that the tdECM hydrogel promotes M2 macrophage polarization, thereby exerting an anti-inflammatory effect in vivo. Furthermore, utilizing tdECM as a carrier for the sustained release of tendon-derived stem cells exosomes (TDSCs-Exos), our findings from both in vitro and in vivo studies indicate that the tdECM hydrogel, in conjunction with exosomes, demonstrated a pronounced synergistic enhancement in modulating inflammation, promoting M2 macrophage polarization, and facilitating tendon regeneration and repair efficacy. These results suggest its potential as a promising therapeutic strategy for tendon disorders.
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Affiliation(s)
- Danmei Li
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Shuai Li
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Shukun He
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Hongpu He
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Guangxun Yuan
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Binbin Ma
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Yijun Zhang
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Chengjie Yuan
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Zhiqin Liu
- Department of Orthopaedics, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, 412007, China
| | - Zhenhan Deng
- Department of Orthopaedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
- Geriatrics Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China
| | - Jian Xu
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
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An Y, Su G, Chen W, Song J, Chai M, Zhu L, Zhang Z. Research progress on the mechanisms of microglial extracellular vesicles affecting the prognosis of ischemic stroke. Neurochem Int 2025; 185:105949. [PMID: 40015338 DOI: 10.1016/j.neuint.2025.105949] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Revised: 01/26/2025] [Accepted: 02/13/2025] [Indexed: 03/01/2025]
Abstract
Ischemic stroke is the major type of stroke and one of the main causes of morbidity, mortality, and long-term disability worldwide. Microglia play a complex and crucial role in stroke. They are the primary immune cells in the brain and can rapidly respond to the pathological changes caused by stroke. They promote neuroprotection and repair after ischemic stroke through various mechanisms, such as activation and polarization, dynamic interactions with other cells (neurons, astrocytes, oligodendrocytes, vascular endothelial cells, etc.), and phagocytosis to clear dead cell debris. Among the multiple pathways through which microglia exert their neuroprotective effects, the secretion of extracellular vesicles is one of the most important. The focus of this review is to analyze the latest progress in research on ischemic stroke related to microglia-derived extracellular vesicles, discuss their mechanisms of action, and provide new strategies for improving stroke prognosis. To obtain relevant articles, we conducted a comprehensive search in Pubmed and Web of Science, with keywords related to ischemic stroke and microglia-derived extracellular vesicles or exosomes. A total of 59 articles were included in the review. Existing studies have shown that after a stroke occurs, microglia release extracellular vesicles containing proteins, nucleic acids, metabolites, etc. These vesicles target corresponding receptor cells and can slow down the development of stroke and improve stroke outcomes through various means, such as reducing neuronal apoptosis, inhibiting neuronal autophagy, suppressing neuronal ferroptosis, preventing neuronal pyroptosis, alleviating inflammatory responses, reducing glial scar formation, promoting myelin regeneration and repair, and facilitating blood-brain barrier repair.
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Affiliation(s)
- Yang An
- Department of Neurology, Lanzhou University Second Hospital, 730030 Lanzhou, Gansu, China
| | - Gang Su
- Institute of Genetics, School of Basic Medical Sciences, Lanzhou University, 730030 Lanzhou, Gansu, China
| | - Wei Chen
- Department of Neurology, Lanzhou University Second Hospital, 730030 Lanzhou, Gansu, China
| | - Jinyang Song
- Department of Neurology, Lanzhou University Second Hospital, 730030 Lanzhou, Gansu, China
| | - Miao Chai
- Department of Neurology, Lanzhou University Second Hospital, 730030 Lanzhou, Gansu, China
| | - Longni Zhu
- Department of Neurology, Lanzhou University Second Hospital, 730030 Lanzhou, Gansu, China
| | - Zhenchang Zhang
- Department of Neurology, Lanzhou University Second Hospital, 730030 Lanzhou, Gansu, China.
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Aakel N, Mohammed R, Fathima A, Kerzabi R, Abdallah A, Ibrahim WN. Role of Exosome in Solid Cancer Progression and Its Potential Therapeutics in Cancer Treatment. Cancer Med 2025; 14:e70941. [PMID: 40344389 PMCID: PMC12063069 DOI: 10.1002/cam4.70941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Revised: 04/14/2025] [Accepted: 04/28/2025] [Indexed: 05/11/2025] Open
Abstract
BACKGROUND Exosomes are extracellular vesicles ranging from 40 to 100 nm in diameter that mediate intercellular communication by transferring proteins, lipids, nucleic acids, and other metabolites. In the context of cancer, exosomes influence the tumor microenvironment by carrying regulatory RNAs such as miRNA, circRNA, and lncRNA. They originate from various cells, including adipocytes, fibroblasts, and hepatocellular carcinoma (HCC) cells, and can either promote or inhibit cancer progression through pathways like MAPK and PI3K-Akt. AIM This review aims to explore the role of exosomes in the progression of solid cancers, emphasizing their self-induced activation mechanisms and how they modulate tumor behavior. METHODOLOGY A comprehensive review of recent literature was conducted, focusing on studies that investigated the biological functions of exosomes in solid tumor progression, including their molecular cargo, cellular origin, and involvement in signaling pathways. RESULTS Findings from multiple studies indicate that cancer-derived exosomes contribute to tumor proliferation, metastasis, and therapy resistance by enhancing communication within the tumor microenvironment. These vesicles activate oncogenic pathways and can serve as biomarkers or therapeutic targets due to their role in disease modulation. CONCLUSION Exosomes play a pivotal role in solid cancer progression and offer significant potential in advancing our understanding of tumor biology. Their capacity to influence key signaling pathways and facilitate intercellular communication makes them promising candidates for novel diagnostic and therapeutic strategies.
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Affiliation(s)
- Nada Aakel
- Department of Biomedical ScienceCollege of Health Sciences, QU Health, Qatar UniversityDohaQatar
| | - Rawdhah Mohammed
- Department of Biomedical ScienceCollege of Health Sciences, QU Health, Qatar UniversityDohaQatar
| | - Assela Fathima
- Department of Biomedical ScienceCollege of Health Sciences, QU Health, Qatar UniversityDohaQatar
| | - Rabia Kerzabi
- Department of Biomedical ScienceCollege of Health Sciences, QU Health, Qatar UniversityDohaQatar
| | - Atiyeh Abdallah
- Department of Biomedical ScienceCollege of Health Sciences, QU Health, Qatar UniversityDohaQatar
| | - Wisam Nabeel Ibrahim
- Department of Biomedical ScienceCollege of Health Sciences, QU Health, Qatar UniversityDohaQatar
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Qi L, Luo DZ, Li H, Yan J, He W. Macrophage-driven exosomes regulate the progression of cardiovascular disease. Front Pharmacol 2025; 16:1563800. [PMID: 40371346 PMCID: PMC12075947 DOI: 10.3389/fphar.2025.1563800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Accepted: 04/07/2025] [Indexed: 05/16/2025] Open
Abstract
Exosomes, as vital mediators of intercellular communication, play a critical role in the progression of cardiovascular disease (CVD). Recently, macrophage-derived exosomes (Mφ-Exos) have garnered increasing attention because of their significant potential in early diagnosis, pathological processes, and therapeutic applications for CVD. Exosomes contain diverse nucleic acids (e.g., miRNAs, mRNAs, and long noncoding RNAs (lncRNAs)) and proteins, which serve as specific biomarkers that regulate various stages of CVD. For example, miRNAs encapsulated within exosomes (e.g., miR-21, miR-133a, and miR-155) are closely associated with atherosclerosis, myocardial infarction, coronary artery disease, and stroke, and changes in their abundance can serve as diagnostic and prognostic indicators. Additionally, the composition of Mφ-Exos, including miRNAs, lipids, and proteins, plays a significant role in the initiation, progression, and inflammation of CVD. Research on Mφ-Exos provides new directions for early diagnosis, mechanistic exploration, and novel therapeutic targets in CVD. However, challenges remain regarding exosome isolation and identification technologies. Future studies need to further explore the biological properties of exosomes and develop more efficient, economical, and straightforward isolation methods. This review summarizes the multifaceted regulatory roles of Mφ-Exos in CVD, encompassing key processes such as inflammation, angiogenesis, metabolism, and cell death. Research has shown that M1-Exos promote the progression and exacerbation of CVD through pro-inflammatory and pro-fibrotic mechanisms, while M2-Exos demonstrate significant therapeutic potential via anti-inflammatory, pro-angiogenic, and metabolic reprogramming pathways. These findings not only reveal the complex mechanisms of Mφ-Exos in CVD but also provide new perspectives and potential targets for early diagnosis and precision treatment of the disease.
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Affiliation(s)
- Liao Qi
- Pengzhou Hospital of Traditional Chinese Medicine, Pengzhou, China
| | - De-Zhu Luo
- Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - HuLi Li
- West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - JianWen Yan
- Pengzhou Hospital of Traditional Chinese Medicine, Pengzhou, China
| | - WenJie He
- Pengzhou Hospital of Traditional Chinese Medicine, Pengzhou, China
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Yin D, Wang P, Hao Y, Yue W, Jiang X, Yao K, Wang Y, Hang X, Xiao A, Zhou J, Lin L, Rao Z, Wu H, Liu F, Dong Z, Wu M, Xu C, Huang J, Chang H, Fan Y, Yu X, Yu C, Chang L, Li M. A battery-free nanofluidic intracellular delivery patch for internal organs. Nature 2025:10.1038/s41586-025-08943-x. [PMID: 40307560 DOI: 10.1038/s41586-025-08943-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 03/26/2025] [Indexed: 05/02/2025]
Abstract
The targeted delivery of therapeutics to internal organs to, for example, promote healing or apoptosis holds promise in the treatment of numerous diseases1-4. Currently, the prevailing delivery modality relies on the circulation; however, this modality has substantial efficiency, safety and/or controllability limitations5-9. Here we report a battery-free, chipless, soft nanofluidic intracellular delivery (NanoFLUID) patch that provides enhanced and customized delivery of payloads in targeted internal organs. The chipless architecture and the flexible nature of thin functional layers facilitate integration with internal organs. The nanopore-microchannel-microelectrode structure enables safe, efficient and precise electroperforation of the cell membrane, which in turn accelerates intracellular payload transport by approximately 105 times compared with conventional diffusion methods while operating under relatively low-amplitude pulses (20 V). Through evaluations of the NanoFLUID patch in multiple in vivo scenarios, including treatment of breast tumours and acute injury in the liver and modelling tumour development, we validated its efficiency, safety and controllability for organ-targeted delivery. NanoFLUID-mediated in vivo transfection of a gene library also enabled efficient screening of essential drivers of breast cancer metastasis in the lung and liver. Through this approach, DUS2 was identified as a lung-specific metastasis driver. Thus, NanoFLUID represents an innovative bioelectronic platform for the targeted delivery of payloads to internal organs to treat various diseases and to uncover new insights in biology.
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Affiliation(s)
- Dedong Yin
- Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
- State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
- Institute of Science and Technology of National Health Commission, Beijing, China
| | - Pan Wang
- State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
| | - Yongcun Hao
- MOE Key Laboratory of Micro and Nano Systems for Aerospace, School of Mechanical Engineering, Northwestern Polytechnical University, Xi'an, China
- Ningbo Institute of Northwestern Polytechnical University, Ningbo, China
| | - Wei Yue
- Interdisciplinary Eye Research Institute (EYE-X Institute), Bengbu Medical University, Bengbu, China
| | - Xinran Jiang
- Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
| | - Kuanming Yao
- Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China
| | - Yuqiong Wang
- Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
| | - Xinxin Hang
- Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
| | - Ao Xiao
- Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
| | - Jingkun Zhou
- Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China
| | - Long Lin
- Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
| | - Zhoulyu Rao
- Materials Research Laboratory, University of Illinois Urbana-Champaign, Urbana, IL, USA
| | - Han Wu
- Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
| | - Feng Liu
- Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
| | - Zaizai Dong
- Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
| | - Meng Wu
- Ministry of Education Key Laboratory of Protein Science, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China
| | - Chenjie Xu
- Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China
| | - Jiandong Huang
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Materials Innovation Institute for Life Sciences and Energy (MILES), HKU-SIRI, Shenzhen, China
| | - Honglong Chang
- MOE Key Laboratory of Micro and Nano Systems for Aerospace, School of Mechanical Engineering, Northwestern Polytechnical University, Xi'an, China
| | - Yubo Fan
- Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
| | - Xinge Yu
- Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China.
- Institute of Digital Medicine, City University of Hong Kong, Hong Kong, China.
- Hong Kong Institute for Clean Energy, City University of Hong Kong, Hong Kong, China.
| | - Cunjiang Yu
- Materials Research Laboratory, University of Illinois Urbana-Champaign, Urbana, IL, USA.
- Department of Electrical and Computer Engineering, Department of Materials Science and Engineering, Department of Bioengineering, Department of Mechanical Science and Engineering, Nick Holonyak Micro and Nanotechnology Laboratory, Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, Urbana, IL, USA.
| | - Lingqian Chang
- Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
| | - Mo Li
- State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
- National Clinical Research Center for Obstetrics and Gynecology, Third Hospital, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China.
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Sulipta JS, Jeong H, Hong S. Polydopamine as a versatile optical indicator for colorimetric and fluorescence-based biosensing. Biomater Sci 2025; 13:2261-2273. [PMID: 40111266 DOI: 10.1039/d5bm00084j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/22/2025]
Abstract
Beyond their well-established adhesive properties, polydopamine (pDA) and pDA-like materials are emerging as superior alternatives to conventional optical indicators in biosensing applications due to their exceptional biocompatibility, tunable optical properties, and high sensitivity, arising from their eumelanin-like physicochemical characteristics. These materials attract significant attention for their ability to function as optical probes and transducers, enabling precise and sensitive detection in complex biological environments. This review highlights recent advancements in developing pDA-based optical probes, emphasizing strategies for fine-tuning synthetic parameters to optimize material properties, clarifying the fundamental sensing mechanisms underlying pDA-based systems, and exploring their potential roles in addressing global healthcare challenges. By facilitating early disease detection, real-time monitoring, and targeted therapeutic intervention, pDA-based optical probes offer transformative solutions to pressing biomedical needs. Through a comprehensive examination of cutting-edge research, this review aims to illuminate how the unique attributes of pDA materials drive innovation in biosensing technologies and contribute to improved healthcare outcomes.
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Affiliation(s)
- Jena Subhra Sulipta
- Department of Physics and Chemistry, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea.
| | - Haejin Jeong
- Department of Physics and Chemistry, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea.
| | - Seonki Hong
- Department of Physics and Chemistry, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea.
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Zeng W, Zhang Y, Wang X, Wang S, Lin T, Su T, Jin Y, Yuan Y, Luo M, Zhong Y, Li L, Zhang D, Gong M, Cheng J, Liu J, Liu S, Wang W, Yang L, Yang H. Chemical Affinity Capture of Plasma Extracellular Vesicles Enables Efficient and Large-Scale Proteomic Identification of Prostate Cancer Biomarkers. ACS NANO 2025; 19:15896-15911. [PMID: 40248970 DOI: 10.1021/acsnano.5c01564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/19/2025]
Abstract
The serum prostate-specific antigen (PSA) testing is widely used for prostate cancer (PCa) screening but suffers from poor specificity, leading to unnecessary biopsies and overtreatment. The significant potential of extracellular vesicles (EVs) in cancer diagnosis has driven the development of efficient methods to isolate and identify EV biomarkers from large-scale clinical samples. Here, we systematically evaluate five commonly used EV isolation techniques through proteomic profiling of plasma-derived EVs, endorsing TiO2-based chemical affinity capture as a superior approach for analyzing EVs from complex clinical samples. This method demonstrates exceptional advantages in speed, throughput, reproducibility, and protein coverage. Using this optimized workflow, we analyzed plasma EVs from 80 patients with PCa and benign prostatic hyperplasia (BPH), identifying growth differentiation factor 15 (GDF15) as a compelling biomarker with a predictive power (AUC) of 0.908 for PCa. Extensive validation across independent cohorts comprising 457 samples, including plasma EVs and prostate tissues, confirmed GDF15's ability to distinguish PCa from BPH and stratify PCa stages. Notably, the combination of GDF15 with PSA further enhanced diagnostic efficiency, particularly for patients in the PSA diagnostic gray zone. This study establishes a robust workflow for EV protein analysis in large clinical cohorts and highlights EV-GDF15 as a promising biomarker for noninvasive PCa diagnosis.
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Affiliation(s)
- Wenjuan Zeng
- Liver Surgery and NHC Key Lab of Transplant Engineering and Immunology, Institutes for Systems Genetics; National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu610041, China
- Sichuan Provincial Engineering Laboratory of Pathology in Clinical Application, West China Hospital, Sichuan University, Chengdu610041, China
| | - Yong Zhang
- Liver Surgery and NHC Key Lab of Transplant Engineering and Immunology, Institutes for Systems Genetics; National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu610041, China
- Sichuan Provincial Engineering Laboratory of Pathology in Clinical Application, West China Hospital, Sichuan University, Chengdu610041, China
| | - Xinyuan Wang
- Proteomics and Metabolomics Core Facilities, West China Hospital, Sichuan University, Chengdu610041, China
| | - Shisheng Wang
- Liver Surgery and NHC Key Lab of Transplant Engineering and Immunology, Institutes for Systems Genetics; National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu610041, China
- Sichuan Provincial Engineering Laboratory of Pathology in Clinical Application, West China Hospital, Sichuan University, Chengdu610041, China
| | - Tianhai Lin
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu610041, China
| | - Tao Su
- Proteomics and Metabolomics Core Facilities, West China Hospital, Sichuan University, Chengdu610041, China
| | - Youmei Jin
- Proteomics and Metabolomics Core Facilities, West China Hospital, Sichuan University, Chengdu610041, China
| | - Yujia Yuan
- Liver Surgery and NHC Key Lab of Transplant Engineering and Immunology, Institutes for Systems Genetics; National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu610041, China
- Sichuan Provincial Engineering Laboratory of Pathology in Clinical Application, West China Hospital, Sichuan University, Chengdu610041, China
| | - Mengqi Luo
- Proteomics and Metabolomics Core Facilities, West China Hospital, Sichuan University, Chengdu610041, China
| | - Yi Zhong
- Proteomics and Metabolomics Core Facilities, West China Hospital, Sichuan University, Chengdu610041, China
| | - Li Li
- Liver Surgery and NHC Key Lab of Transplant Engineering and Immunology, Institutes for Systems Genetics; National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu610041, China
- Sichuan Provincial Engineering Laboratory of Pathology in Clinical Application, West China Hospital, Sichuan University, Chengdu610041, China
| | - Dingkun Zhang
- Liver Surgery and NHC Key Lab of Transplant Engineering and Immunology, Institutes for Systems Genetics; National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu610041, China
- Sichuan Provincial Engineering Laboratory of Pathology in Clinical Application, West China Hospital, Sichuan University, Chengdu610041, China
| | - Meng Gong
- Liver Surgery and NHC Key Lab of Transplant Engineering and Immunology, Institutes for Systems Genetics; National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu610041, China
- Sichuan Provincial Engineering Laboratory of Pathology in Clinical Application, West China Hospital, Sichuan University, Chengdu610041, China
| | - Jingqiu Cheng
- Liver Surgery and NHC Key Lab of Transplant Engineering and Immunology, Institutes for Systems Genetics; National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu610041, China
- Sichuan Provincial Engineering Laboratory of Pathology in Clinical Application, West China Hospital, Sichuan University, Chengdu610041, China
| | - Jingping Liu
- Liver Surgery and NHC Key Lab of Transplant Engineering and Immunology, Institutes for Systems Genetics; National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu610041, China
- Sichuan Provincial Engineering Laboratory of Pathology in Clinical Application, West China Hospital, Sichuan University, Chengdu610041, China
| | - Shan Liu
- Sichuan Provincial Key Laboratory for Human Disease Gene Study, Department of Medical Genetics, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu610072, China
| | - Weiya Wang
- Department of Pathology, West China Hospital, Sichuan University, Chengdu610041, China
| | - Lu Yang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu610041, China
| | - Hao Yang
- Liver Surgery and NHC Key Lab of Transplant Engineering and Immunology, Institutes for Systems Genetics; National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu610041, China
- Proteomics and Metabolomics Core Facilities, West China Hospital, Sichuan University, Chengdu610041, China
- Sichuan Provincial Engineering Laboratory of Pathology in Clinical Application, West China Hospital, Sichuan University, Chengdu610041, China
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Barth I, Lee H. Nanophotonic sensing and label-free imaging of extracellular vesicles. LIGHT, SCIENCE & APPLICATIONS 2025; 14:177. [PMID: 40295495 PMCID: PMC12037801 DOI: 10.1038/s41377-025-01866-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/04/2025] [Revised: 04/08/2025] [Accepted: 04/10/2025] [Indexed: 04/30/2025]
Abstract
This review examines imaging-based nanophotonic biosensing and interferometric label-free imaging, with a particular focus on vesicle detection. It specifically compares dielectric and plasmonic metasurfaces for label-free protein and extracellular vesicle detection, highlighting their respective advantages and limitations. Key topics include: (i) refractometric sensing principles using resonant dielectric and plasmonic surfaces; (ii) state-of-the-art developments in both plasmonic and dielectric nanostructured resonant surfaces; (iii) a detailed comparison of resonance characteristics, including amplitude, quality factor, and evanescent field enhancement; and (iv) the relationship between sensitivity, near-field enhancement, and analyte overlap in different sensing platforms. The review provides insights into the fundamental differences between plasmonic and dielectric platforms, discussing their fabrication, integration potential, and suitability for various analyte sizes. It aims to offer a unified, application-oriented perspective on the potential of these resonant surfaces for biosensing and imaging, aiming at addressing topics of interest for both photonics experts and potential users of these technologies.
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Affiliation(s)
- Isabel Barth
- Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02115, USA.
| | - Hakho Lee
- Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02115, USA.
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41
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Rong J, Li YY, Wang X, Wang JN, Song M. Non-coding RNAs in adipose-derived stem cell exosomes: Mechanisms, therapeutic potential, and challenges in wound healing. World J Stem Cells 2025; 17:102917. [PMID: 40308889 PMCID: PMC12038460 DOI: 10.4252/wjsc.v17.i4.102917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 12/23/2024] [Accepted: 03/21/2025] [Indexed: 04/23/2025] Open
Abstract
The treatment of complex wounds presents a significant clinical challenge due to the limited availability of standardized therapeutic options. Adipose-derived stem cell exosomes (ADSC-Exos) are promising for their capabilities to enhance angiogenesis, mitigate oxidative stress, modulate inflammatory pathways, support skin cell regeneration, and promote epithelialization. These exosomes deliver non-coding RNAs, including microRNAs, long non-coding RNAs, and circular RNAs, which facilitate collagen remodeling, reduce scar formation, and expedite wound healing. This study reviews the mechanisms, therapeutic roles, and challenges of non-coding RNA-loaded ADSC-Exos in wound healing and identifies critical directions for future research. It aims to provide insights for researchers into the potential mechanisms and clinical applications of ADSC-Exos non-coding RNAs in wound healing.
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Affiliation(s)
- Jian Rong
- Department of Burns and Plastic Surgery, The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730050, Gansu Province, China
- Department of Plateau Medicine, The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Yao-Yao Li
- Department of Burns and Plastic Surgery, The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730050, Gansu Province, China
- Department of Plateau Medicine, The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Xin Wang
- Department of Burns and Plastic Surgery, The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730050, Gansu Province, China
- Department of Plateau Medicine, The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Jia-Ning Wang
- Department of Burns and Plastic Surgery, The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730050, Gansu Province, China
- Department of Plateau Medicine, The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Mei Song
- Department of Burns and Plastic Surgery, The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730050, Gansu Province, China
- Department of Plateau Medicine, The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730050, Gansu Province, China.
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Hsu CW, Fang YC, Li JF, Cheng CA. Decoding Complex Biological Milieus: SHINER's Approach to Profiling and Functioning of Extracellular Vesicle Subpopulations. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2025:e2503638. [PMID: 40255212 DOI: 10.1002/smll.202503638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/24/2025] [Indexed: 04/22/2025]
Abstract
Extracellular vesicles (EVs) are celebrated for their pivotal roles in cellular communication and their potential in disease diagnosis and therapeutic applications. However, their inherent heterogeneity acts as a double-edged sword, complicating the isolation of specific EV subpopulations. Conventional EV isolation methods often fall short, relying on biophysical properties, while affinity-based techniques may compromise EV integrity and utility with harsh recovery conditions. To address these limitations, the SHINER (subpopulation homogeneous isolation and nondestructive EV release) workflow is introduced, which redefines how EVs are isolated and recoverd, featuring the innovative SWITCHER (switchable extracellular vesicle releaser) tool. The SHINER workflow facilitates the precise purification and gentle recovery of target EV subpopulations from complex biological mixtures, preserving their structural integrity and biological functionality. Importantly, SHINER demonstrates exceptional adaptability to multiple markers and clinical applications. It not only enhances the ability to trace EV origins for accurate disease diagnosis but also advances fundamental EV research and provides standardized EV materials for therapeutic innovations. By improving the understanding of EVs and enabling the development of personalized diagnostics and treatments, SHINER propels EV-based science into new frontiers of advanced medicine, offering transformative potential for healthcare.
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Affiliation(s)
- Chen-Wei Hsu
- School of Pharmacy, College of Medicine, National Taiwan University, Taipei, 10050, Taiwan
| | - Yao-Ching Fang
- School of Pharmacy, College of Medicine, National Taiwan University, Taipei, 10050, Taiwan
| | - Jhih-Fong Li
- School of Pharmacy, College of Medicine, National Taiwan University, Taipei, 10050, Taiwan
| | - Chi-An Cheng
- School of Pharmacy, College of Medicine, National Taiwan University, Taipei, 10050, Taiwan
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43
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Vafadar A, AlaviManesh S, Maddahi ME, Alizadeh M, Movahedpour A, Savardashtaki A. Exosome biosensors for detection of prostate cancer. Clin Chim Acta 2025; 571:120243. [PMID: 40090566 DOI: 10.1016/j.cca.2025.120243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 03/10/2025] [Accepted: 03/11/2025] [Indexed: 03/18/2025]
Abstract
Prostate cancer (PCa) is a highly life-threatening disease in men, causing numerous deaths worldwide. As PCa is often diagnosed at a late stage, current diagnostic methods can be invasive and sometimes lead to unnecessary treatments. Therefore, new non-invasive approaches are needed to detect biomarkers for more rapid and accurate PCa diagnosis. Exosomes, extracellular vesicles, provide valuable insights into cellular health and disease progression. Recent studies have indicated the potential use of exosomes as biomarkers for diagnosing PCa. Developing fast, reliable, and sensitive methods for exosome detection is essential. Biosensors, powerful analytical tools for biological samples, have become increasingly crucial in exosome analysis. This review summarizes recent advancements in biosensor technology for exosome detection and provides insights into future perspectives. The goal is to encourage innovative biosensor-based approaches for exosome detection and contribute to the early diagnosis and clinical monitoring of various diseases.
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Affiliation(s)
- Asma Vafadar
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sajad AlaviManesh
- Student Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Mohammad Ehsan Maddahi
- Department of Medical Biotechnology, Faculty of Medicine, Shahid Sadoughi University of Medical Science, Yazd, Iran
| | - Mehdi Alizadeh
- Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ahmad Movahedpour
- Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.
| | - Amir Savardashtaki
- Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran; Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
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Wang X, Zhou Z, Zhang Y, Liu J, Qin T, Zhou W, Li Q, Wu X, Xue K, Cao H, Su Y, Zhao S, Lu C, Jiang T, Yin G, Chen J. Exosome-shuttled miR-5121 from A2 astrocytes promotes BSCB repair after traumatic SCI by activating autophagy in vascular endothelial cells. J Nanobiotechnology 2025; 23:291. [PMID: 40229869 PMCID: PMC11998472 DOI: 10.1186/s12951-025-03365-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2025] [Accepted: 04/01/2025] [Indexed: 04/16/2025] Open
Abstract
Spinal cord injury (SCI) is a severe neurological disorder that significantly impacts patients' quality of life. Following SCI, the blood-spinal cord barrier (BSCB) is destroyed, leading to ischemia and hypoxia, which further exacerbates the imbalance in the spinal cord microenvironment. A2-type astrocytes, which arise under ischemic and hypoxic conditions, have been reported to promote SCI repair. However, the roles of exosomes derived from A2 astrocytes (A2-Exos) in SCI have not been explored. This study aims to investigate the role of A2-Exos in SCI repair, particularly in BSCB restoration, and to elucidate its potential mechanisms. GEO database analysis, western blotting, and immunofluorescence were used to detect A2 astrocyte polarization after SCI in mice. In vitro, A2 astrocytes were obtained through hypoxia induction, and A2-Exos were extracted via ultracentrifugation. An in vivo SCI model and a series of in vitro experiments demonstrated the reparative effects of A2-Exos on BSCB following SCI. Furthermore, miRNA sequencing analysis and rescue experiments confirmed the role of miRNAs in A2-Exos-mediated BSCB repair. Finally, luciferase assays and western blotting were performed to investigate the underlying mechanisms. The results showed that A2-Exos promote motor function recovery and BSCB repair in mice following SCI. In vitro, A2-Exos facilitated BSCB reconstruction and endothelial cell autophagy. miRNA sequencing identified miR-5121 as the most significantly enriched miRNA in A2-Exos, suggesting its involvement in BSCB repair and autophagy regulation. AKT2 was identified as a potential downstream target of miR-5121. Functional gain- and loss-of-function experiments further validated the miR-5121/AKT2 axis. Finally, we demonstrated that the AKT2/mTOR/p70S6K pathway may mediate the effects of miR-5121 in A2-Exos on BSCB repair.
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Affiliation(s)
- Xiaowei Wang
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China
- Jiangsu Institute of Functional Reconstruction and Rehabilitation, Jiangsu Provincial Clinical Research Institute, Nanjing, Jiangsu, 210029, China
- Department of Orthopedics, Maanshan People's Hospital, Maanshan, Anhui, 243000, China
| | - Zihan Zhou
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China
- Jiangsu Institute of Functional Reconstruction and Rehabilitation, Jiangsu Provincial Clinical Research Institute, Nanjing, Jiangsu, 210029, China
| | - Yu Zhang
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China
- Jiangsu Institute of Functional Reconstruction and Rehabilitation, Jiangsu Provincial Clinical Research Institute, Nanjing, Jiangsu, 210029, China
| | - Jiayun Liu
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China
- Jiangsu Institute of Functional Reconstruction and Rehabilitation, Jiangsu Provincial Clinical Research Institute, Nanjing, Jiangsu, 210029, China
| | - Tao Qin
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China
- Jiangsu Institute of Functional Reconstruction and Rehabilitation, Jiangsu Provincial Clinical Research Institute, Nanjing, Jiangsu, 210029, China
| | - Wei Zhou
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China
- Jiangsu Institute of Functional Reconstruction and Rehabilitation, Jiangsu Provincial Clinical Research Institute, Nanjing, Jiangsu, 210029, China
| | - Qingqing Li
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China
- Jiangsu Institute of Functional Reconstruction and Rehabilitation, Jiangsu Provincial Clinical Research Institute, Nanjing, Jiangsu, 210029, China
| | - Xincan Wu
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China
- Jiangsu Institute of Functional Reconstruction and Rehabilitation, Jiangsu Provincial Clinical Research Institute, Nanjing, Jiangsu, 210029, China
| | - Kaixiao Xue
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China
- Jiangsu Institute of Functional Reconstruction and Rehabilitation, Jiangsu Provincial Clinical Research Institute, Nanjing, Jiangsu, 210029, China
| | - Heng Cao
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China
- Jiangsu Institute of Functional Reconstruction and Rehabilitation, Jiangsu Provincial Clinical Research Institute, Nanjing, Jiangsu, 210029, China
| | - Yunxin Su
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China
- Jiangsu Institute of Functional Reconstruction and Rehabilitation, Jiangsu Provincial Clinical Research Institute, Nanjing, Jiangsu, 210029, China
| | - Shujie Zhao
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China
- Jiangsu Institute of Functional Reconstruction and Rehabilitation, Jiangsu Provincial Clinical Research Institute, Nanjing, Jiangsu, 210029, China
| | - Chun Lu
- Department of Microbiology, Nanjing Medical University, Nanjing, 211166, China.
| | - Tao Jiang
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
- Jiangsu Institute of Functional Reconstruction and Rehabilitation, Jiangsu Provincial Clinical Research Institute, Nanjing, Jiangsu, 210029, China.
| | - Guoyong Yin
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
- Jiangsu Institute of Functional Reconstruction and Rehabilitation, Jiangsu Provincial Clinical Research Institute, Nanjing, Jiangsu, 210029, China.
| | - Jian Chen
- Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
- Jiangsu Institute of Functional Reconstruction and Rehabilitation, Jiangsu Provincial Clinical Research Institute, Nanjing, Jiangsu, 210029, China.
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Kim M, Park S, Lee N, Kim D, Kim D, Jin Y, Lee SJ, Hong JJ, Lee H. Advanced MicroRNA delivery for lung inflammatory therapy: surfactant protein A controls cellular internalisation and degradation of extracellular vesicles. Thorax 2025; 80:322-334. [PMID: 39632081 PMCID: PMC12015036 DOI: 10.1136/thorax-2024-221793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Accepted: 11/06/2024] [Indexed: 12/07/2024]
Abstract
INTRODUCTION Alveolar macrophages (AMs) are the first line of defence against pathogens that initiate an inflammatory response in the lungs and exhibit a strong affinity for surfactant protein A (SP-A). Extracellular vesicles (EVs) have emerged as a promising drug delivery platform due to their minimal cytotoxicity. However, precise targeting of specific cell types and the rapid lysosomal degradation of EVs within recipient cells remain persistent challenges. METHOD In this study, we explored the biological significance of SP-A-EVs as novel drug delivery systems for combating lung inflammation. We first verified that respiratory EVs express SP-A receptor (SP-R210), facilitating the conjugation of SP-A with EVs. The delivery efficiency, cellular internalisation pathways and therapeutic effects were evaluated using an in vivo mouse model. RESULTS SP-A-EVs were robustly internalised into AMs both in vitro and in vivo. Furthermore, our investigation revealed that the toll-like receptor 4-mediated endocytosis pathway was employed for the uptake of SP-A-EVs, significantly delaying their degradation compared with natural EVs, which primarily followed the conventional lysosomal degradation pathway within AMs. In a functional study, we successfully loaded anti-inflammatory microRNA (let-7b) into SP-A-EVs, leading to the suppression of AM activation and the alleviation of lung inflammation induced by lipopolysaccharide. CONCLUSION These findings underscore the potential of SP-A-EVs as highly effective drug delivery systems for targeted therapeutics in lung-related disorders, capitalising on the strong affinity between AMs and SP-A and the modulation of cellular internalisation.
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Affiliation(s)
- Miji Kim
- Department of Biology and Chemistry, Changwon National University, Changwon, South Korea
- Korea Research Institute of Bioscience and Biotechnology National Primate Research Center, Ochang, South Korea
- University of Science and Technology, Daejeon, South Korea
| | - Sujeong Park
- Department of Biology and Chemistry, Changwon National University, Changwon, South Korea
- University of Science and Technology, Daejeon, South Korea
- Environmental Disease Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon, South Korea
| | - Nayoung Lee
- Department of Biology and Chemistry, Changwon National University, Changwon, South Korea
| | - Dohyun Kim
- Department of Biology and Chemistry, Changwon National University, Changwon, South Korea
| | - Dongwoo Kim
- Department of Biology and Chemistry, Changwon National University, Changwon, South Korea
| | - Yang Jin
- Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Seon-Jin Lee
- University of Science and Technology, Daejeon, South Korea
- Environmental Disease Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon, South Korea
| | - Jung Joo Hong
- Korea Research Institute of Bioscience and Biotechnology National Primate Research Center, Ochang, South Korea
- University of Science and Technology, Daejeon, South Korea
| | - Heedoo Lee
- Department of Biology and Chemistry, Changwon National University, Changwon, South Korea
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46
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Dong W, Chen M, Wang C, Jia M, Zhang H, Ou J, Wei Y. Honeycomb-Shaped Supermacroporous Adsorbent Integrating Size-Exclusion and Selective Chemisorption Enables High-Efficiency Extraction and Analysis of Exosomes from Plasma. Anal Chem 2025; 97:7510-7517. [PMID: 40150816 DOI: 10.1021/acs.analchem.5c00702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/29/2025]
Abstract
As cell secretions, exosomes play an important role in disease diagnosis, but the extraction of high-purity exosomes from body fluids faces great challenges. To address this issue, this work creates an excellently selective adsorbent by modifying the zwitterionic polymer carrying choline phosphate on the surface of honeycomb-shaped supermacroporous silica, which integrates chemisorption and size-exclusion principles. The results indicate that the supermacropore with a thin pore wall allows exosomes to enter and thereby be adsorbed by the polymer via specific multivalent interaction and, meanwhile, excludes large cell debris and microvesicles. Moreover, the amphiphilic polymer can inhibit the adsorption of coexisting proteins. Taking advantage of these properties, the adsorbent can extract higher purity exosomes in a simpler way over "gold standard" ultracentrifugation and normal adsorbents. Furthermore, the in situ lysis of adsorbed exosomes simplifies the subsequent analysis and enhances the sensitivity. Consequently, 422 proteins are identified in the exosomes extracted from healthy human plasma, which is higher than that obtained by ultracentrifugation. For plasma from colorectal cancer patients, 62 upregulated and 165 downregulated proteins are identified and can be used as potential biomarkers. In conclusion, the adsorbent can serve as a platform for the high-efficiency extraction of exosomes in clinical diagnostic research.
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Affiliation(s)
- Wenzhuo Dong
- Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an 710127, China
| | - Mengxi Chen
- College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
| | - Chenyang Wang
- Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an 710127, China
| | - Mengqian Jia
- Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an 710127, China
| | - Haiyang Zhang
- College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
| | - Junjie Ou
- Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an 710127, China
| | - Yinmao Wei
- Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an 710127, China
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Shen H, Chen J, Liu M, Zhao M, Hu D, Xie F, Jin Q, Xiao D, Peng Z, Qin T, Rao D, Huang D. Research progress of extracellular vesicles derived from mesenchymal stem cells in the treatment of neurodegenerative diseases. Front Immunol 2025; 16:1496304. [PMID: 40242755 PMCID: PMC12000061 DOI: 10.3389/fimmu.2025.1496304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Accepted: 03/10/2025] [Indexed: 04/18/2025] Open
Abstract
As the world's population ages, neurodegenerative diseases are becoming more widely acknowledged as serious global health and socioeconomic issues. Although many resources have been devoted to the research of these illnesses, little progress has been made in the creation of novel diagnostic and therapeutic approaches. Extracellular vesicles (EVs) are released by all cell types and contain proteins, microRNAs, mRNAs, and other biologically active molecules. EVs play an important role in intercellular communication as well as in the regulation of neuroinflammation. Determining the mechanisms by which EVs contribute to the pathogenesis of neurodegenerative diseases will aid in the development of new therapeutic approaches and diagnostic tools. Mesenchymal stem cells (MSCs) have been shown in studies to control immunological responses, promote the growth of new brain connections, promote the production of blood vessels, and heal damaged tissues. There is growing evidence that MSCs' ability to treat patients is mostly due to the neurotrophic compounds they secrete through EVs. Since their tiny size allows them to pass through biological barriers and reach injured parts of the central nervous system, MSC-derived extracellular vesicles (MSC-EVs) retain many of the therapeutic qualities of their parent MSCs. This review discusses the role of EVs in neurodegenerative diseases and highlights the potential of MSC-EVs in the treatment of neurodegenerative diseases. The paper also examines the challenges that still need to be overcome and the prospects for using MSC-EVs to treat neurodegenerative illnesses.
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Affiliation(s)
- Haibin Shen
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Jie Chen
- Department of Laboratory Medicine, Yongchuan Hospital of Chongqing Medical University, Chongqing, Yongchuan, China
| | - Meijin Liu
- Laboratory Medicine, People’s Hospital of Ganzhou Economic Development Zone, Ganzhou, China
| | - Minghong Zhao
- Laboratory Medicine, Guizhou Aerospace Hospital, Zunyi, China
| | - Die Hu
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Fangfang Xie
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Qing Jin
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Dewang Xiao
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
| | - Zongbo Peng
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
| | - Tao Qin
- Laboratory Medicine, Guizhou Aerospace Hospital, Zunyi, China
| | - Dingyu Rao
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Defa Huang
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
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Xie Z, Zhao S, Deng R, Tang X, Feng L, Xie S, Pi Y, Chen M, Chang K. Logic-Measurer: A Multienzyme-Assisted Ultrasensitive Circuit for Logical Detection of Exosomal MicroRNAs. ACS NANO 2025; 19:12222-12236. [PMID: 40108772 DOI: 10.1021/acsnano.5c00258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/22/2025]
Abstract
The logic profiling of exosomal microRNAs (miRNAs) offers broad potential applications in the accurate diagnosis and staging of cancer. However, the logical detection of low-abundance exosomal miRNAs in complex clinical samples remains challenging. This study introduces a logic analysis system termed "Measurer" (a multi-enzyme-assisted ultrasensitive circuit) that offers ultrasensitive and versatile method for detecting multiple exosomal miRNAs. The Logic-Measurer comprises three modules: a stem-loop hairpin-enhanced CRISPR/Cas13a, a polymerase-driven primer exchange reaction, and an exonuclease III-mediated fluorescence output. The efficient Logic-Measurer was switched by the faster rate of trans-cleavage activity of Cas13a due to its improved affinity for hairpin RNA structures. The mechanistic model of hairpin-enhanced CRISPR/Cas13a was confirmed by molecular dynamics simulations. The Logic-Measurer accurately detected exosomal miRNA-21 or miRNA-375 down to 2.1 and 4.4 fM, with superior specificity, and enabled in situ detection of miRNA-21 and miRNA-375 in as low as 1.4 × 102 particles/mL exosomes via membrane fusion. In addition, this method demonstrated 87.3 and 82.1% accuracy in the diagnosis and early detection of breast cancer, respectively, among a cohort of 315 individuals. Subsequent subgroup analysis further confirmed the method's ability to accurately differentiate estrogen receptor-positive patients from healthy individuals. Therefore, the Logic-Measurer offers valuable insights into the development of a CRISPR/Cas-based enhanced diagnostic platform and the next generation of diagnostic technology based on enzyme circuits.
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Affiliation(s)
- Zuowei Xie
- Department of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Shuang Zhao
- Department of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Ruijia Deng
- Department of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Xiaoqi Tang
- Department of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Liu Feng
- Department of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Shuang Xie
- Department of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Yan Pi
- Department of Rehabilitation Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China
| | - Ming Chen
- Department of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Kai Chang
- Department of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China
- State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, 30 Gaotanyan, Shapingba District, Chongqing 400038, China
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Feng X, Shen A, Zhang W, Jia S, Iliuk A, Wang Y, Zhang W, Zhang Y, Tao WA, Hu L. High-throughput capture and in situ protein analysis of extracellular vesicles by chemical probe-based array. Nat Protoc 2025; 20:1057-1081. [PMID: 39438698 DOI: 10.1038/s41596-024-01082-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Accepted: 09/25/2024] [Indexed: 10/25/2024]
Abstract
Extracellular vesicles (EVs) are small particles with phospholipid bilayers that carry a diverse range of cargoes including nucleic acids, proteins and metabolites. EVs have important roles in various cellular processes and are increasingly recognized for their ubiquitous role in cell-cell communications and potential applications in therapeutics and diagnostics. Although many methods have been developed for the characterization and measurement of EVs, analyzing them from biofluids remains a challenge with regard to throughput and sensitivity. Recently, we introduced an approach to facilitate high-throughput analysis of EVs from trace amounts of sample. In this method, an amphiphile-dendrimer supramolecular probe (ADSP) is coated onto a nitrocellulose membrane for array-based capture and to enable an in situ immunoblotting assay. Here, we describe the protocol for our array-based method of EV profiling. We describe an enhanced version of the method that incorporates an automated printing workstation, ensuring high throughput and reproducibility. We further demonstrate the use of our array to profile specific glycosylations on the EV surface using click chemistry of an azide group introduced by metabolic labeling. In this protocol, the synthesis of ADSP and the fabrication of ADSP nitrocellulose membrane array can be completed on the same day. EVs are efficiently captured from biological or clinical samples through a 30-min incubation, followed by an immunoblotting assay within a 3-h window, thus providing a high-throughput platform for EV isolation and in situ targeted analysis of EV proteins and their modifications.
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Affiliation(s)
- Xin Feng
- Center for Supramolecular Chemical Biology, State Key Laboratory of Supramolecular Structure and Materials, School of Life Sciences, Jilin University, Changchun, China
- School of Natural Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, New South Wales, Australia
| | - Ao Shen
- Center for Supramolecular Chemical Biology, State Key Laboratory of Supramolecular Structure and Materials, School of Life Sciences, Jilin University, Changchun, China
- School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Wei Zhang
- School of Natural Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, New South Wales, Australia
| | - Shengnan Jia
- Center for Supramolecular Chemical Biology, State Key Laboratory of Supramolecular Structure and Materials, School of Life Sciences, Jilin University, Changchun, China
| | - Anton Iliuk
- Department of Biochemistry, Purdue University, West Lafayette, IN, USA
| | - Yuling Wang
- School of Natural Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, New South Wales, Australia
| | - Wenke Zhang
- Center for Supramolecular Chemical Biology, State Key Laboratory of Supramolecular Structure and Materials, School of Life Sciences, Jilin University, Changchun, China
| | - Ying Zhang
- Department of Chemistry and NHC Key Laboratory of Glycoconjugates Research, Fudan University, Shanghai, China.
| | - W Andy Tao
- Department of Biochemistry, Purdue University, West Lafayette, IN, USA.
| | - Lianghai Hu
- Center for Supramolecular Chemical Biology, State Key Laboratory of Supramolecular Structure and Materials, School of Life Sciences, Jilin University, Changchun, China.
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50
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Wang R, Wang Z, Zhang M, Zhong D, Zhou M. Application of photosensitive microalgae in targeted tumor therapy. Adv Drug Deliv Rev 2025; 219:115519. [PMID: 39955076 DOI: 10.1016/j.addr.2025.115519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 01/02/2025] [Accepted: 01/18/2025] [Indexed: 02/17/2025]
Abstract
Microalgae present a novel and multifaceted approach to cancer therapy by modulating the tumor-associated microbiome (TAM) and the tumor microenvironment (TME). Through their ability to restore gut microbiota balance, reduce inflammation, and enhance immune responses, microalgae contribute to improved cancer treatment outcomes. As photosynthetic microorganisms, microalgae exhibit inherent anti-tumor, antioxidant, and immune-regulating properties, making them valuable in photodynamic therapy and tumor imaging due to their capacity to generate reactive oxygen species. Additionally, microalgae serve as effective drug delivery vehicles, leveraging their biocompatibility and unique structural properties to target the TME more precisely. Microalgae-based microrobots further expand their therapeutic potential by autonomously navigating complex biological environments, offering a promising future for precision-targeted cancer treatments. We position microalgae as a multifunctional agent capable of modulating TAM, offering novel strategies to enhance TME and improve the efficacy of cancer therapies.
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Affiliation(s)
- Ruoxi Wang
- Eye Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310029, China; Institute of Translational Medicine, Zhejiang University, Hangzhou 310029, China; Zhejiang University-Ordos City Etuoke Banner Joint Research Center, Haining 314400, China
| | - Zhouyue Wang
- Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Zhejiang University School of Medicine, Zhejiang University, Haining 314400, China
| | - Min Zhang
- Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Zhejiang University School of Medicine, Zhejiang University, Haining 314400, China
| | - Danni Zhong
- Institute of Translational Medicine, Zhejiang University, Hangzhou 310029, China
| | - Min Zhou
- Eye Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310029, China; Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Zhejiang University School of Medicine, Zhejiang University, Haining 314400, China; Institute of Translational Medicine, Zhejiang University, Hangzhou 310029, China; Zhejiang University-Ordos City Etuoke Banner Joint Research Center, Haining 314400, China.
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