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Venturini J, Chakraborty A, Baysal MA, Tsimberidou AM. Developments in nanotechnology approaches for the treatment of solid tumors. Exp Hematol Oncol 2025; 14:76. [PMID: 40390104 PMCID: PMC12090476 DOI: 10.1186/s40164-025-00656-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2025] [Accepted: 04/16/2025] [Indexed: 05/21/2025] Open
Abstract
Nanotechnology has revolutionized cancer therapy by introducing advanced drug delivery systems that enhance therapeutic efficacy while reducing adverse effects. By leveraging various nanoparticle platforms-including liposomes, polymeric nanoparticles, and inorganic nanoparticles-researchers have improved drug solubility, stability, and bioavailability. Additionally, new nanodevices are being engineered to respond to specific physiological conditions like temperature and pH variations, enabling controlled drug release and optimizing therapeutic outcomes. Beyond drug delivery, nanotechnology plays a crucial role in the theranostic field due to the functionalization of specific materials that combine tumor detection and targeted treatment features. This review analyzes the clinical impact of nanotechnology, spanning from early-phase trials to pivotal phase 3 studies that have obtained regulatory approval, while also offering a critical perspective on the preclinical domain and its translational potential for future human applications. Despite significant progress, greater attention must be placed on key challenges, such as biocompatibility barriers and the lack of regulatory standardization, to ensure the successful translation of nanomedicine into routine clinical practice.
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Affiliation(s)
- Jacopo Venturini
- Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Unit 455, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
- Current Affiliation: Department of Medical Oncology, Careggi University Hospital, Florence, Italy
| | - Abhijit Chakraborty
- Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Unit 455, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Mehmet A Baysal
- Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Unit 455, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Apostolia M Tsimberidou
- Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Unit 455, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
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Yaman S, Devoe T, Aygun U, Parlatan U, Bobbili MR, Karim AH, Grillari J, Durmus NG. EV-Lev: extracellular vesicle isolation from human plasma using microfluidic magnetic levitation device. LAB ON A CHIP 2025; 25:1439-1451. [PMID: 39918033 DOI: 10.1039/d4lc00830h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/12/2025]
Abstract
Biological nanomaterials have unique magnetic and density characteristics that can be employed to isolate them into subpopulations. Extracellular nanovesicles (EVs) are crucial for cellular communication; however, their isolation poses significant challenges due to their diverse sizes and compositions. We present EV-Lev, a microfluidic magnetic levitation technique for high-throughput, selective isolation of small EVs (<200 nm) from human plasma. EV-Lev overcomes the challenges posed by the subtle buoyancy characteristics of EVs, whose small size and varied densities complicate traditional magnetic levitation techniques. It employs antibody-coated polymer beads of varying densities, integrating immuno-affinity and microfluidics to isolate EVs from sub-milliliter plasma volumes efficiently. It facilitates rapid, simultaneous sorting of EV subpopulations based on surface markers, such as CD9, CD63, and CD81, achieving high yield and purity. Subsequent size and morphology analyses confirmed that the isolated EVs maintain their structural integrity. EV-Lev could help uncover the cargo and function of EV subpopulations associated with multiple diseases including cancer, infectious diseases and help to discover potential biomarkers in small volume samples, while offering a portable, cost-effective, and straightforward assay scheme.
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Affiliation(s)
- Sena Yaman
- Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University, Stanford, CA 94305-5281, USA.
| | - Tessa Devoe
- Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University, Stanford, CA 94305-5281, USA.
- Brown University, Providence, RI 02912, USA
| | - Ugur Aygun
- Canary Center for Cancer Early Detection, Department of Radiology, Stanford University, Stanford, CA 94304, USA
- Department of Electrical and Electronics Engineering, Koç University, Istanbul, Turkiye
| | - Ugur Parlatan
- Canary Center for Cancer Early Detection, Department of Radiology, Stanford University, Stanford, CA 94304, USA
| | - Madhusudhan Reddy Bobbili
- Canary Center for Cancer Early Detection, Department of Radiology, Stanford University, Stanford, CA 94304, USA
- Institute of Molecular Biotechnology, Department of Biotechnology, BOKU University, 1190 Wien, Austria
- Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, 1200 Wien, Austria
| | - Asma H Karim
- Canary Center for Cancer Early Detection, Department of Radiology, Stanford University, Stanford, CA 94304, USA
| | - Johannes Grillari
- Institute of Molecular Biotechnology, Department of Biotechnology, BOKU University, 1190 Wien, Austria
- Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, 1200 Wien, Austria
| | - Naside Gozde Durmus
- Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University, Stanford, CA 94305-5281, USA.
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3
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Shinde U, Balasinor NH, Ravichandran V, Kumar AS, Gunasekaran VP. "Extracellular Vesicle DNA: Advances and Applications as a Non-Invasive Biomarker in Disease Diagnosis and Treatment". Clin Chim Acta 2025; 568:120125. [PMID: 39793847 DOI: 10.1016/j.cca.2025.120125] [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: 01/06/2025] [Accepted: 01/06/2025] [Indexed: 01/13/2025]
Abstract
Extracellular vesicles (EVs) are nanoscale, membrane-enclosed structures released by cells into the extracellular milieu. These vesicles encapsulate a diverse array of molecular constituents, including nucleic acids, proteins, and lipids, which provide insights into the physiological or pathological conditions of their parent cells. Despite their potential, the study of EV-derived DNA (EV-DNA) has gathered relatively limited attention. This review aims to present a thorough examination of the emerging knowledge surrounding the utility of EV-DNA as a non-invasive biomarker across a spectrum of diseases. The review delves into various mechanisms underlying DNA packaging within EVs and the prevalent methodologies employed for extraction of EV-DNA. The relevance of EV-DNA is assessed across numerous health conditions, notably cancer, cardiovascular diseases, neurodegenerative disorders, infectious diseases, and pregnancy-related complications. The use of EV-DNA for cancer mutation detection has demonstrated remarkable sensitivity and specificity, thereby enhancing both diagnostic accuracy and therapeutic monitoring. In the context of cardiovascular diseases, EV-DNA serves as a predictive marker for events such as myocardial infarctions and shows a correlation with the severity of the disease. With respect to neurodegenerative conditions, including Parkinson's and Alzheimer's, EV-DNA contributes to the understanding of disease mechanisms and progression. Additionally, it plays an essential role in modulating immune tolerance and facilitating communication between maternal and fetal systems. Although there is a pressing need for standardized protocols for EV isolation and DNA analysis to facilitate clinical implementation, the prospect of EV-DNA as a non-invasive biomarker for diagnostic and prognostic purposes across diverse pathological conditions is considerable.
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Affiliation(s)
- Uma Shinde
- Center for Drug Discovery and Development, Amity Institute of Biotechnology, Amity University Mumbai (AUM), Maharashtra, India
| | - Nafisa Huseni Balasinor
- ICMR-National Institute for Research in Reproductive and Child Health (ICMR- NIRRCH), Parel, Mumbai, India
| | - Vinothkannan Ravichandran
- Center for Drug Discovery and Development, Amity Institute of Biotechnology, Amity University Mumbai (AUM), Maharashtra, India
| | - Aw Santhosh Kumar
- Center for Drug Discovery and Development, Amity Institute of Biotechnology, Amity University Mumbai (AUM), Maharashtra, India; California University of Science & Medicine, CA, United States of America
| | - Vinoth Prasanna Gunasekaran
- Center for Drug Discovery and Development, Amity Institute of Biotechnology, Amity University Mumbai (AUM), Maharashtra, India.
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Molinski JH, Parwal S, Zhang JXJ. Laser-Patterning of Micromagnets for Immuno-Magnetophoretic Exosome Capture. SMALL METHODS 2024; 8:e2400388. [PMID: 39003624 DOI: 10.1002/smtd.202400388] [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: 03/17/2024] [Revised: 06/23/2024] [Indexed: 07/15/2024]
Abstract
Efficient isolation and patterning of biomolecules is a vital step within sample preparation for biomolecular analysis, with numerous diagnostic and therapeutic applications. For exosomes, nanoscale lipid-bound biomolecules, efficient isolation is challenging due to their minute size and resultant behavior within biofluids. This study presents a method for the rapid isolation and patterning of magnetically tagged exosomes via rationally designed micromagnets. Micromagnet fabrication utilizes a novel, scalable, and high-throughput laser-based fabrication approach that enables patterning at microscale lateral resolution (<50 µm) without lithographic processing and is agnostic to micromagnet geometry. Laser-based processing allows for flexible and tunable device configurations, and herein magnetophoretic capture within both an open-air microwell and an enclosed microfluidic system is demonstrated. Patterned micromagnets enhance localized gradient fields throughout the fluid medium, resulting in rapid and high efficiency magnetophoretic separation, with capture efficiencies nearing 70% after just 1s within open-air microwells, and throughputs upward of 3 mL h-1 within enclosed microfluidic systems. Using this microchip architecture, immunomagnetic exosome isolation and patterning directly from undiluted plasma samples is further achieved. Lastly, a FEA-based modeling workflow is introduced to characterize and optimize micromagnet unit cells, simulating magnetophoretic capture zones for a given micromagnet geometry.
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Affiliation(s)
- John H Molinski
- Thayer School of Engineering at Dartmouth, Hanover, NH, 03755, USA
| | - Siddhant Parwal
- Thayer School of Engineering at Dartmouth, Hanover, NH, 03755, USA
| | - John X J Zhang
- Thayer School of Engineering at Dartmouth, Hanover, NH, 03755, USA
- Dartmouth Cancer Center, Dartmouth Health, Lebanon, NH, 03766, USA
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5
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Kim T, Choodinatha HK, Kim KS, Shin K, Kim HJ, Park JY, Hong JW, Lee LP. Understanding the role of soluble proteins and exosomes in non-invasive urine-based diagnosis of preeclampsia. Sci Rep 2024; 14:24117. [PMID: 39406891 PMCID: PMC11482518 DOI: 10.1038/s41598-024-75080-2] [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: 05/17/2024] [Accepted: 10/01/2024] [Indexed: 10/19/2024] Open
Abstract
Preeclampsia is a hypertensive disorder of pregnancy that can lead to stillbirth and preterm birth if not treated promptly. Currently, the diagnosis of preeclampsia relies on clinical symptoms such as hypertension and proteinuria, along with invasive blood tests. Here, we investigate the role of soluble proteins and exosomes in noninvasive diagnosing preeclampsia non-invasively using maternal urine and urine-derived exosomes. We quantified the levels of particles and the presence of TSG101 and CD63 in urine and urinary exosomes via the biologically intact exosome separation technology (BEST) platform. Then, we obtained higher levels of soluble proteins such as fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) from urine as it was than urinary exosomes. Compared to commercial blood tests, the sensitivity of the sFlt-1/PlGF ratio was found to be 4.0 times higher in urine tests and 1.5 times higher in tests utilizing urine-derived exosomes. Our findings offer promising possibilities for the early and non-invasive identification of high-risk individuals at risk of preeclampsia, allowing for comprehensive preventive management.
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Affiliation(s)
- Taewoon Kim
- Department of Bionanotechnology, Graduate School, Hanyang University, Seoul, 04763, Korea
| | - Harshitha Kallubhavi Choodinatha
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
- Seoul National University, Seoul, Korea
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Kwang Sik Kim
- Department of Bionanotechnology, Graduate School, Hanyang University, Seoul, 04763, Korea
| | - Kyusoon Shin
- Department of Bionanotechnology, Graduate School, Hanyang University, Seoul, 04763, Korea
| | - Hyeon Ji Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
- Seoul National University, Seoul, Korea
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jee Yoon Park
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
- Seoul National University, Seoul, Korea.
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
| | - Jong Wook Hong
- Department of Bionanotechnology, Graduate School, Hanyang University, Seoul, 04763, Korea.
- Department of Medical and Digital Engineering, Graduate School, Hanyang University, Seoul, 04763, Korea.
- Department of Bionanoengineering, Hanyang University, 15588, Ansan, Gyeonggi-do, Korea.
| | - Luke P Lee
- Harvard Medical School, Department of Medicine, Harvard University, Brigham and Women's Hospital, Boston, MA, USA.
- Department of Bioengineering, University of California at Berkeley, Berkeley, CA, USA.
- Department of Electrical Engineering and Computer Science, University of California at Berkeley, Berkeley, CA, USA.
- Department of Biophysics, Institute of Quantum Biophysics, Sungkyunkwan University, Suwon, Korea.
- Department of Chemistry & Nanoscience, Ewha Womans University, Seoul, Korea.
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Oshins R, Greenberg Z, Tai YL, Zhao D, Wang X, Mehrad B, He M, Patel I, Khartabil L, Zhou H, Brantly M, Khodayari N. Extracellular Vesicle-Associated Neutrophil Elastase Activates Hepatic Stellate Cells and Promotes Liver Fibrogenesis via ERK1/2 Pathway. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.08.20.608832. [PMID: 39229038 PMCID: PMC11370372 DOI: 10.1101/2024.08.20.608832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 09/05/2024]
Abstract
Liver fibrosis associated with increased mortality is caused by activation of hepatic stellate cells and excessive production and accumulation of extracellular matrix in response to fibrotic insults. It has been shown that in addition to liver inflammation, systemic inflammation also contributes to liver fibrogenesis. A deeper understanding of mechanisms that control liver fibrotic response to intra- and extra-hepatic inflammation is essential to develop novel clinical strategies against this disease. Extracellular vesicles (EV) have been recognized as immune mediators that facilitate activation of hepatic stellate cells. In inflammatory diseases, activated neutrophils release neutrophil elastase (NE) bound to EV, which has been identified as a significant contributor to inflammation by promoting immune cell activation. Here, we aimed to explore the role of inflammation derived plasma EV-associated NE in liver fibrogenesis and its potential mechanisms. We show EV-associated NE induces activation, proliferation and migration of hepatic stellate cells by promoting activation of the ERK1/2 signaling pathway. This effect did not occur through EV without surface NE, and Sivelestat, a NE inhibitor, inhibited activation of the ERK1/2 signaling pathway mediated by EV-associated NE. Moreover, we found plasma EV-associated NE increases deposition of collagen1 and α-smooth muscle actin in the liver of a mouse model of liver fibrosis (Mdr2-/-). Notably, this effect does not occur in control mice without preexisting liver disease. These data suggest that EV-associated NE is a pro-fibrogenic factor for hepatic stellate cell activation via the ERK1/2 signaling pathway in pre-existing liver injuries. Inhibition of the plasma EV-associated NE in inflammatory conditions may be a therapeutic target for liver fibrosis in patients with inflammatory diseases.
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Affiliation(s)
- Regina Oshins
- Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine; University of Florida, Gainesville, Florida, USA
| | - Zachary Greenberg
- Department of Pharmaceutics, College of Pharmacy; University of Florida, Gainesville, Florida, USA
| | - Yun-Ling Tai
- Department of Microbiology and Immunology; Virginia Commonwealth University, Richmond VA Medical Center, Richmond, Virginia, USA
| | - Derrick Zhao
- Department of Microbiology and Immunology; Virginia Commonwealth University, Richmond VA Medical Center, Richmond, Virginia, USA
| | - Xuan Wang
- Department of Microbiology and Immunology; Virginia Commonwealth University, Richmond VA Medical Center, Richmond, Virginia, USA
| | - Borna Mehrad
- Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine; University of Florida, Gainesville, Florida, USA
| | - Mei He
- Department of Pharmaceutics, College of Pharmacy; University of Florida, Gainesville, Florida, USA
| | - Ishan Patel
- Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine; University of Florida, Gainesville, Florida, USA
| | - Laith Khartabil
- Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine; University of Florida, Gainesville, Florida, USA
| | - Huiping Zhou
- Department of Microbiology and Immunology; Virginia Commonwealth University, Richmond VA Medical Center, Richmond, Virginia, USA
| | - Mark Brantly
- Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine; University of Florida, Gainesville, Florida, USA
| | - Nazli Khodayari
- Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine; University of Florida, Gainesville, Florida, USA
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7
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Zhu X, Lin X, Hu L, Wang L, Zhu Q. Harnessing crosstalk between extracellular vesicles and viruses for disease diagnostics and therapeutics. EXTRACELLULAR VESICLES AND CIRCULATING NUCLEIC ACIDS 2024; 5:358-370. [PMID: 39697627 PMCID: PMC11648403 DOI: 10.20517/evcna.2024.30] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 06/18/2024] [Accepted: 06/24/2024] [Indexed: 12/20/2024]
Abstract
Extracellular vesicles (EVs) are increasingly acknowledged as important mediators of intercellular communication, closely related to the occurrence and development of a variety of diseases. Numerous studies have demonstrated that EVs play a multifaceted role in the infection process of viral diseases, elucidating their ability to both facilitate viral spread and inhibit infection progression. These versatile entities not only enhance infection rates and widen the scope of viral infection through the transmission of entire viruses or viral genomes, but also trigger antiviral responses and prompt cytokine secretion near the infection site, thereby fortifying the host's defense mechanisms and safeguarding neighboring cells against infection. This complicated crosstalk between EVs and viral infections prompts a deeper exploration into their roles in potential clinical applications. In this review, we aim to encapsulate the recent advances in understanding the intricate interplay between viruses and EVs, shedding light on the mechanisms underlying this vesicle-to-virion crosstalk. Furthermore, we underscore the significance of harnessing this knowledge for diagnostic and therapeutic functions in combating viral diseases.
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Affiliation(s)
- Xinxi Zhu
- National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
- Key Laboratory of Heart and Lung, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China
| | - Xiuhui Lin
- Key Laboratory of Heart and Lung, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China
| | - Liang Hu
- National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
| | - Liangxing Wang
- Key Laboratory of Heart and Lung, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China
| | - Qingfu Zhu
- National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
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8
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Greenberg ZF, Ali S, Schmittgen TD, Han S, Hughes SJ, Graim KS, He M. Peptide-based capture-and-release purification of extracellular vesicles and statistical algorithm enabled quality assessment. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.02.06.578050. [PMID: 38370748 PMCID: PMC10871196 DOI: 10.1101/2024.02.06.578050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/20/2024]
Abstract
Circulating extracellular vesicles (EVs) have gained significant attention for discovering tumor biomarkers. However, isolating EVs with well-defined homogeneous populations from complex biological samples is challenging. Different isolation methods have been found to derive different EV populations carrying different molecular contents, which confounds current investigations and hinders subsequent clinical translation. Therefore, standardizing and building a rigorous assessment of isolated EV quality associated with downstream molecular analysis is essential. To address this need, we introduce a statistical algorithm (ExoQuality Index, EQI) by integrating multiple EV characterizations (size, particle concentration, zeta potential, total protein, and RNA), enabling direct EV quality assessment and comparisons between different isolation methods. We also introduced a novel capture-release isolation approach using a pH-responsive peptide conjugated with NanoPom magnetic beads (ExCy) for simple, fast, and homogeneous EV isolation from various biological fluids. Bioinformatic analysis of next-generation sequencing (NGS) data of EV total RNAs from pancreatic cancer patient plasma samples using our novel EV isolation approach and quality index strategy illuminates how this approach improves the identification of tumor associated molecular markers. Results showed higher human mRNA coverage compared to existing isolation approaches in terms of both pancreatic cancer pathways and EV cellular component pathways using gProfiler pathway analysis. This study provides a valuable resource for researchers, establishing a workflow to prepare and analyze EV samples carefully and contributing to the advancement of reliable and rigorous EV quality assessment and clinical translation.
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Affiliation(s)
- Zachary F. Greenberg
- Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida 32610, United States
| | - Samantha Ali
- Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida 32610, United States
| | - Thomas D. Schmittgen
- Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida 32610, United States
| | - Song Han
- Department of Surgery, College of Medicine, University of Florida, Gainesville, Florida 32610, United States
| | - Steven J. Hughes
- Department of Surgery, College of Medicine, University of Florida, Gainesville, Florida 32610, United States
| | - Kiley S. Graim
- Department of Computer & Information Science & Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, Florida, 32610, USA
| | - Mei He
- Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida 32610, United States
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Rayamajhi S, Sipes J, Tetlow AL, Saha S, Bansal A, Godwin AK. Extracellular Vesicles as Liquid Biopsy Biomarkers across the Cancer Journey: From Early Detection to Recurrence. Clin Chem 2024; 70:206-219. [PMID: 38175602 DOI: 10.1093/clinchem/hvad176] [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: 07/30/2023] [Accepted: 09/26/2023] [Indexed: 01/05/2024]
Abstract
BACKGROUND Cancer is a dynamic process and thus requires highly informative and reliable biomarkers to help guide patient care. Liquid-based biopsies have emerged as a clinical tool for tracking cancer dynamics. Extracellular vesicles (EVs), lipid bilayer delimited particles secreted by cells, are a new class of liquid-based biomarkers. EVs are rich in selectively sorted biomolecule cargos, which provide a spatiotemporal fingerprint of the cell of origin, including cancer cells. CONTENT This review summarizes the performance characteristics of EV-based biomarkers at different stages of cancer progression, from early malignancy to recurrence, while emphasizing their potential as diagnostic, prognostic, and screening biomarkers. We discuss the characteristics of effective biomarkers, consider challenges associated with the EV biomarker field, and report guidelines based on the biomarker discovery pipeline. SUMMARY Basic science and clinical trial studies have shown the potential of EVs as precision-based biomarkers for tracking cancer status, with promising applications for diagnosing disease, predicting response to therapy, and tracking disease burden. The multi-analyte cargos of EVs enhance the performance characteristics of biomarkers. Recent technological advances in ultrasensitive detection of EVs have shown promise with high specificity and sensitivity to differentiate early-cancer cases vs healthy individuals, potentially outperforming current gold-standard imaging-based cancer diagnosis. Ultimately, clinical translation will be dictated by how these new EV biomarker-based platforms perform in larger sample cohorts. Applying ultrasensitive, scalable, and reproducible EV detection platforms with better design considerations based upon the biomarker discovery pipeline should guide the field towards clinically useful liquid biopsy biomarkers.
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Affiliation(s)
- Sagar Rayamajhi
- Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, United States
| | - Jared Sipes
- Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, United States
| | - Ashley L Tetlow
- Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, United States
| | - Souvik Saha
- Division of Gastroenterology and Hepatology, University of Kansas Health System, Kansas City, KS, United States
| | - Ajay Bansal
- Division of Gastroenterology and Hepatology, University of Kansas Health System, Kansas City, KS, United States
- The University of Kansas Cancer Center, University of Kansas Medical Center, Kansas City, KS, United States
| | - Andrew K Godwin
- Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, United States
- The University of Kansas Cancer Center, University of Kansas Medical Center, Kansas City, KS, United States
- Division of Genomic Diagnostics, University of Kansas Health System, Kansas City, KS, United States
- Kansas Institute for Precision Medicine, University of Kansas Medical Center, Kansas City, KS, United States
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10
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Zhang Y, Zhao L, Li Y, Wan S, Yuan Z, Zu G, Peng F, Ding X. Advanced extracellular vesicle bioinformatic nanomaterials: from enrichment, decoding to clinical diagnostics. J Nanobiotechnology 2023; 21:366. [PMID: 37798669 PMCID: PMC10557264 DOI: 10.1186/s12951-023-02127-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Accepted: 09/24/2023] [Indexed: 10/07/2023] Open
Abstract
Extracellular vesicles (EVs) are membrane nanoarchitectures generated by cells that carry a variety of biomolecules, including DNA, RNA, proteins and metabolites. These characteristics make them attractive as circulating bioinformatic nanocabinets for liquid biopsy. Recent advances on EV biology and biogenesis demonstrate that EVs serve as highly important cellular surrogates involved in a wide range of diseases, opening up new frontiers for modern diagnostics. However, inefficient methods for EV enrichment, as well as low sensitivity of EV bioinformatic decoding technologies, hinder the use of EV nanocabinet for clinical diagnosis. To overcome these challenges, new EV nanotechnology is being actively developed to promote the clinical translation of EV diagnostics. This article aims to present the emerging enrichment strategies and bioinformatic decoding platforms for EV analysis, and their applications as bioinformatic nanomaterials in clinical settings.
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Affiliation(s)
- Yawei Zhang
- State Key Laboratory of Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, Nanjing, 210023, China
| | - Liang Zhao
- State Key Laboratory of Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, Nanjing, 210023, China
| | - Yaocheng Li
- State Key Laboratory of Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, Nanjing, 210023, China
| | - Shuangshuang Wan
- State Key Laboratory of Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, Nanjing, 210023, China
| | - Zhiyao Yuan
- Department of Periodontology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China.
| | - Guangyue Zu
- CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China
| | - Fei Peng
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02114, USA
| | - Xianguang Ding
- State Key Laboratory of Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, Nanjing, 210023, China.
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11
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Kozhevnikova D, Chernyshev V, Yashchenok A. Progress in Isolation and Molecular Profiling of Small Extracellular Vesicles via Bead-Assisted Platforms. BIOSENSORS 2023; 13:688. [PMID: 37504087 PMCID: PMC10377709 DOI: 10.3390/bios13070688] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 06/21/2023] [Accepted: 06/25/2023] [Indexed: 07/29/2023]
Abstract
Tremendous interest in research of small extracellular vesicles (sEVs) is driven by the participation of vesicles in a number of biological processes in the human body. Being released by almost all cells of the body, sEVs present in complex bodily fluids form the so-called intercellular communication network. The isolation and profiling of individual fractions of sEVs secreted by pathological cells are significant in revealing their physiological functions and clinical importance. Traditional methods for isolation and purification of sEVs from bodily fluids are facing a number of challenges, such as low yield, presence of contaminants, long-term operation and high costs, which restrict their routine practical applications. Methods providing a high yield of sEVs with a low content of impurities are actively developing. Bead-assisted platforms are very effective for trapping sEVs with high recovery yield and sufficient purity for further molecular profiling. Here, we review recent advances in the enrichment of sEVs via bead-assisted platforms emphasizing the type of binding sEVs to the bead surface, sort of capture and target ligands and isolation performance. Further, we discuss integration-based technologies for the capture and detection of sEVs as well as future research directions in this field.
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Affiliation(s)
- Daria Kozhevnikova
- Skoltech Center for Photonic Science and Engineering, Skolkovo Institute of Science and Technology Skolkovo Innovation Center, 121205 Moscow, Russia
| | - Vasiliy Chernyshev
- National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov, 117997 Moscow, Russia
| | - Alexey Yashchenok
- Skoltech Center for Photonic Science and Engineering, Skolkovo Institute of Science and Technology Skolkovo Innovation Center, 121205 Moscow, Russia
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12
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Greenberg ZF, Graim KS, He M. Towards artificial intelligence-enabled extracellular vesicle precision drug delivery. Adv Drug Deliv Rev 2023:114974. [PMID: 37356623 DOI: 10.1016/j.addr.2023.114974] [Citation(s) in RCA: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 06/21/2023] [Accepted: 06/22/2023] [Indexed: 06/27/2023]
Abstract
Extracellular Vesicles (EVs), particularly exosomes, recently exploded into nanomedicine as an emerging drug delivery approach due to their superior biocompatibility, circulating stability, and bioavailability in vivo. However, EV heterogeneity makes molecular targeting precision a critical challenge. Deciphering key molecular drivers for controlling EV tissue targeting specificity is in great need. Artificial intelligence (AI) brings powerful prediction ability for guiding the rational design of engineered EVs in precision control for drug delivery. This review focuses on cutting-edge nano-delivery via integrating large-scale EV data with AI to develop AI-directed EV therapies and illuminate the clinical translation potential. We briefly review the current status of EVs in drug delivery, including the current frontier, limitations, and considerations to advance the field. Subsequently, we detail the future of AI in drug delivery and its impact on precision EV delivery. Our review discusses the current universal challenge of standardization and critical considerations when using AI combined with EVs for precision drug delivery. Finally, we will conclude this review with a perspective on future clinical translation led by a combined effort of AI and EV research.
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Affiliation(s)
- Zachary F Greenberg
- Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, 32610, USA
| | - Kiley S Graim
- Department of Computer & Information Science & Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, Florida, 32610, USA
| | - Mei He
- Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, 32610, USA.
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Gong L, Cretella A, Lin Y. Microfluidic systems for particle capture and release: A review. Biosens Bioelectron 2023; 236:115426. [PMID: 37276636 DOI: 10.1016/j.bios.2023.115426] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 05/17/2023] [Accepted: 05/24/2023] [Indexed: 06/07/2023]
Abstract
Microfluidic technology has emerged as a promising tool in various applications, including biosensing, disease diagnosis, and environmental monitoring. One of the notable features of microfluidic devices is their ability to selectively capture and release specific cells, biomolecules, bacteria, and particles. Compared to traditional bulk analysis instruments, microfluidic capture-and-release platforms offer several advantages, such as contactless operation, label-free detection, high accuracy, good sensitivity, and minimal reagent requirements. However, despite significant efforts dedicated to developing innovative capture mechanisms in the past, the release and recovery efficiency of trapped particles have often been overlooked. Many previous studies have focused primarily on particle capture techniques and their efficiency, disregarding the crucial role of successful particle release for subsequent analysis. In reality, the ability to effectively release trapped particles is particularly essential to ensure ongoing, high-throughput analysis. To address this gap, this review aims to highlight the importance of both capture and release mechanisms in microfluidic systems and assess their effectiveness. The methods are classified into two categories: those based on physical principles and those using biochemical approaches. Furthermore, the review offers a comprehensive summary of recent applications of microfluidic platforms specifically designed for particle capture and release. It outlines the designs and performance of these devices, highlighting their advantages and limitations in various target applications and purposes. Finally, the review concludes with discussions on the current challenges faced in the field and presents potential future directions.
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Affiliation(s)
- Liyuan Gong
- Department of Mechanical, Industrial and Systems Engineering, University of Rhode Island, Kingston, RI, 02881, USA
| | - Andrew Cretella
- Department of Mechanical, Industrial and Systems Engineering, University of Rhode Island, Kingston, RI, 02881, USA
| | - Yang Lin
- Department of Mechanical, Industrial and Systems Engineering, University of Rhode Island, Kingston, RI, 02881, USA.
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Sanya DRA, Onésime D. Roles of non-coding RNAs in the metabolism and pathogenesis of bladder cancer. Hum Cell 2023:10.1007/s13577-023-00915-5. [PMID: 37209205 DOI: 10.1007/s13577-023-00915-5] [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: 01/29/2023] [Accepted: 05/07/2023] [Indexed: 05/22/2023]
Abstract
Bladder cancer (BC) is featured as the second most common malignancy of the urinary tract worldwide with few treatments leading to high incidence and mortality. It stayed a virtually intractable disease, and efforts to identify innovative and effective therapies are urgently needed. At present, more and more evidence shows the importance of non-coding RNA (ncRNA) for disease-related study, diagnosis, and treatment of diverse types of malignancies. Recent evidence suggests that dysregulated functions of ncRNAs are closely associated with the pathogenesis of numerous cancers including BC. The detailed mechanisms underlying the dysregulated role of ncRNAs in cancer progression are still not fully understood. This review mainly summarizes recent findings on regulatory mechanisms of the ncRNAs, long non-coding RNAs, microRNAs, and circular RNAs, in cancer progression or suppression and focuses on the predictive values of ncRNAs-related signatures in BC clinical outcomes. A deeper understanding of the ncRNA interactive network could be compelling framework for developing biomarker-guided clinical trials.
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Affiliation(s)
- Daniel Ruben Akiola Sanya
- Micalis Institute, Diversité génomique et fonctionnelle des levures, domaine de Vilvert, Université Paris-Saclay, INRAE, AgroParisTech, 78350, Jouy-en-Josas, France.
| | - Djamila Onésime
- Micalis Institute, Diversité génomique et fonctionnelle des levures, domaine de Vilvert, Université Paris-Saclay, INRAE, AgroParisTech, 78350, Jouy-en-Josas, France
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15
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Meeseepong M, Ghosh G, Shrivastava S, Lee NE. Fluorescence-Enhanced Microfluidic Biosensor Platform Based on Magnetic Beads with Highly Stable ZnO Nanorods for Biomarker Detection. ACS APPLIED MATERIALS & INTERFACES 2023; 15:21754-21765. [PMID: 37104719 DOI: 10.1021/acsami.2c22352] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/11/2023]
Abstract
Existing affinity-based fluorescence biosensing systems for monitoring of biomarkers often utilize a fixed solid substrate immobilized with capture probes limiting their use in continuous or intermittent biomarker detection. Furthermore, there have been challenges of integrating fluorescence biosensors with a microfluidic chip and low-cost fluorescence detector. Herein, we demonstrated a highly efficient and movable fluorescence-enhanced affinity-based fluorescence biosensing platform that can overcome the current limitations by combining fluorescence enhancement and digital imaging. Fluorescence-enhanced movable magnetic beads (MBs) decorated with zinc oxide nanorods (MB-ZnO NRs) were used for digital fluorescence-imaging-based aptasensing of biomolecules with improved signal-to-noise ratio. High stability and homogeneous dispersion of photostable MB-ZnO NRs were obtained by grafting bilayered silanes onto the ZnO NRs. The ZnO NRs formed on MB significantly improved the fluorescence signal up to 2.35 times compared to the MB without ZnO NRs. Moreover, the integration of a microfluidic device for flow-based biosensing enabled continuous measurements of biomarkers in an electrolytic environment. The results showed that highly stable fluorescence-enhanced MB-ZnO NRs integrated with a microfluidic platform have significant potential for diagnostics, biological assays, and continuous or intermittent biomonitoring.
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Affiliation(s)
- Montri Meeseepong
- SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University, Suwon, Gyeonggi-do 16419, Korea
| | - Gargi Ghosh
- School of Advanced Materials Science & Engineering, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, Korea
| | - Sajal Shrivastava
- Symbiosis Centre for Nanoscience and Nanotechnology, Symbiosis International University, Pune 412115, India
| | - Nae-Eung Lee
- SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University, Suwon, Gyeonggi-do 16419, Korea
- School of Advanced Materials Science & Engineering, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, Korea
- Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Suwon, Gyeonggi-do 16419, Korea
- Institute of Quantum Biophysics (IQB), Sungkyunkwan University, Suwon, Gyeonggi-do 16419, Korea
- Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon, Gyeonggi-do 16419, Korea
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Thenrajan T, Alwarappan S, Wilson J. Molecular Diagnosis and Cancer Prognosis-A Concise Review. Diagnostics (Basel) 2023; 13:766. [PMID: 36832253 PMCID: PMC9955694 DOI: 10.3390/diagnostics13040766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 02/09/2023] [Accepted: 02/10/2023] [Indexed: 02/22/2023] Open
Abstract
Cancer is a complicated disease. Globally, it is one of the major causes for morbidity and mortality. A critical challenge associated with it is the difficulty to accurately diagnose it at an early stage. The malignancy due to multistage and heterogeneity that result from genetic and epigenetic modifications poses critical challenge to diagnose and monitor the progress at an early stage. Current diagnostic techniques normally suggest invasive biopsy procedure that can cause further infections and bleeding. Therefore, noninvasive diagnostic methods with high accuracy, safety and earliest detection are the needs of the hour. Herein, we provide a detailed review on the advanced methodologies and protocols developed for the detection of cancer biomarkers based on proteins, nucleic acids and extracellular vesicles. Furthermore, existing challenges and the improvements essential for the rapid, sensitive and noninvasive detection have also been discussed.
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Affiliation(s)
- Thatchanamoorthy Thenrajan
- Polymer Electronics Lab., Department of Bioelectronics and Biosensors, Alagappa University, Karaikudi 630003, Tamil Nadu, India
| | - Subbiah Alwarappan
- CSIR-Central Electrochemical Research Institute, Karaikudi 630003, Tamilnadu, India
| | - Jeyaraj Wilson
- Polymer Electronics Lab., Department of Bioelectronics and Biosensors, Alagappa University, Karaikudi 630003, Tamil Nadu, India
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17
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Taylor ML, Giacalone AG, Amrhein KD, Wilson RE, Wang Y, Huang X. Nanomaterials for Molecular Detection and Analysis of Extracellular Vesicles. NANOMATERIALS (BASEL, SWITZERLAND) 2023; 13:524. [PMID: 36770486 PMCID: PMC9920192 DOI: 10.3390/nano13030524] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 01/23/2023] [Accepted: 01/24/2023] [Indexed: 06/18/2023]
Abstract
Extracellular vesicles (EVs) have emerged as a novel resource of biomarkers for cancer and certain other diseases. Probing EVs in body fluids has become of major interest in the past decade in the development of a new-generation liquid biopsy for cancer diagnosis and monitoring. However, sensitive and specific molecular detection and analysis are challenging, due to the small size of EVs, low amount of antigens on individual EVs, and the complex biofluid matrix. Nanomaterials have been widely used in the technological development of protein and nucleic acid-based EV detection and analysis, owing to the unique structure and functional properties of materials at the nanometer scale. In this review, we summarize various nanomaterial-based analytical technologies for molecular EV detection and analysis. We discuss these technologies based on the major types of nanomaterials, including plasmonic, fluorescent, magnetic, organic, carbon-based, and certain other nanostructures. For each type of nanomaterial, functional properties are briefly described, followed by the applications of the nanomaterials for EV biomarker detection, profiling, and analysis in terms of detection mechanisms.
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Affiliation(s)
| | | | | | | | | | - Xiaohua Huang
- Department of Chemistry, The University of Memphis, Memphis, TN 38152, USA
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18
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Littig JPB, Moellmer R, Agrawal DK, Rai V. Future applications of exosomes delivering resolvins and cytokines in facilitating diabetic foot ulcer healing. World J Diabetes 2023; 14:35-47. [PMID: 36684384 PMCID: PMC9850797 DOI: 10.4239/wjd.v14.i1.35] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 11/22/2022] [Accepted: 12/21/2022] [Indexed: 01/10/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) increases the risk of many lethal and debilitating conditions. Among them, foot ulceration due to neuropathy, vascular disease, or trauma affects the quality of life of millions in the United States and around the world. Physiological wound healing is stalled in the inflammatory phase by the chronicity of inflammation without proceeding to the resolution phase. Despite advanced treatment, diabetic foot ulcers (DFUs) are associated with a risk of amputation. Thus, there is a need for novel therapies to address chronic inflammation, decreased angiogenesis, and impaired granulation tissue formation contributing to the non-healing of DFUs. Studies have shown promising results with resolvins (Rv) and anti-inflammatory therapies that resolve inflammation and enhance tissue healing. But many of these studies have encountered difficulty in the delivery of Rv in terms of efficiency, tissue targetability, and immunogenicity. This review summarized the perspective of optimizing the therapeutic application of Rv and cytokines by pairing them with exosomes as a novel strategy for targeted tissue delivery to treat non-healing chronic DFUs. The articles discussing the T2DM disease state, current research on Rv for treating inflammation, the role of Rv in enhancing wound healing, and exosomes as a delivery vehicle were critically reviewed to find support for the proposition of using Rv and exosomes in combination for DFUs therapy. The literature reviewed suggests the beneficial role of Rv and exosomes and exosomes loaded with anti-inflammatory agents as promising therapeutic agents in ulcer healing.
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Affiliation(s)
- Joshua P B Littig
- Translational Research, Western University of Health Sciences, Pomona, CA 91766, United States
| | - Rebecca Moellmer
- College of Podiatry, Western University of Health Sciences, Pomona, CA 91766, United States
| | - Devendra K Agrawal
- Translational Research, Western University of Health Sciences, Pomona, CA 91766, United States
| | - Vikrant Rai
- Translational Research, Western University of Health Sciences, Pomona, CA 91766, United States
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Applications of Exosomes in Diagnosing Muscle Invasive Bladder Cancer. Pharmaceutics 2022; 14:pharmaceutics14102027. [PMID: 36297462 PMCID: PMC9607910 DOI: 10.3390/pharmaceutics14102027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 09/17/2022] [Accepted: 09/20/2022] [Indexed: 11/30/2022] Open
Abstract
Muscle Invasive Bladder Cancer (MIBC) is a subset of bladder cancer with a significant risk for metastases and death. It accounts for nearly 25% of bladder cancer diagnoses. A diagnostic work-up for MIBC is inclusive of urologic evaluation, radiographic imaging with a CT scan, urinalysis, and cystoscopy. These evaluations, especially cystoscopy, are invasive and carry the risk of secondary health concerns. Non-invasive diagnostics such as urine cytology are an attractive alternative currently being investigated to mitigate the requirement for cystoscopy. A pitfall in urine cytology is the lack of available options with high reliability, specificity, and sensitivity to malignant bladder cells. Exosomes are a novel biomarker source which could resolve some of the concerns with urine cytology, due to the high specificity as the surrogates of tumor cells. This review serves to define muscle invasive bladder cancer, current urine cytology methods, the role of exosomes in MIBC, and exosomes application as a diagnostic tool in MIBC. Urinary exosomes as the specific populations of extracellular vesicles could provide additional biomarkers with specificity and sensitivity to bladder malignancies, which are a consistent source of cellular information to direct clinicians for developing treatment strategies. Given its strong presence and differentiation ability between normal and cancerous cells, exosome-based urine cytology is highly promising in providing a perspective of a patient’s bladder cancer.
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