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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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2
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Tao K, Tao K, Wang J. The potential mechanisms of extracellular vesicles in transfusion-related adverse reactions: Recent advances. Transfus Clin Biol 2025; 32:205-227. [PMID: 40180029 DOI: 10.1016/j.tracli.2025.03.006] [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: 01/15/2025] [Revised: 03/15/2025] [Accepted: 03/25/2025] [Indexed: 04/05/2025]
Abstract
Blood transfusion is an irreplaceable clinical treatment. Blood components are differentiated and stored according to specific guidelines. Storage temperatures and times vary depending on the blood component, but they all release extracellular vesicles (EVs) during storage. Although blood transfusions can be life-saving, they can also cause many adverse transfusion reactions, among which the effects of EVs are of increasing interest to researchers. EVs are submicron particles that vary in size, composition, and surface biomarkers, are encapsulated by a lipid bilayer, and are not capable of self-replication. EVs released by blood cells are important contributors to pathophysiologic states through proinflammatory, coagulant, and immunosuppressive effects, which in turn promote or inhibit the associated disease phenotype. Therefore, this review explores the potential mechanisms of hematopoietic-derived EVs in transfusion-associated adverse reactions and discusses the potential of the latest proteomics tools to be applied to the analysis of EVs in the field of transfusion medicine with a view to reducing the risk of blood transfusion.
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Affiliation(s)
- Keyi Tao
- Panzhihua University, Panzhihua 617000 Sichuan, China
| | - Keran Tao
- Institute of Medicine and Nursing, Hubei University of Medicine, Shiyan 442000 Hubei, China
| | - Jing Wang
- Southwest Medical University, Luzhou 646000 Sichuan, China; Department of Blood Transfusion, The Affiliated Hospital of Southwest Medical University, Luzhou Sichuan, 646000 China.
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3
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Yu HJ, Moon MH. Direct lipid analysis of exosomes in serum by online miniaturized asymmetrical flow field-flow fractionation and electrospray ionization-mass spectrometry: Application to extrahepatic cholangiocarcinoma. J Chromatogr A 2025; 1746:465778. [PMID: 39970688 DOI: 10.1016/j.chroma.2025.465778] [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: 12/17/2024] [Revised: 02/12/2025] [Accepted: 02/13/2025] [Indexed: 02/21/2025]
Abstract
Exosomes are submicron-sized extracellular vesicles involved in immune regulation, tumor metastasis, and cellular communication. Their lipid composition, distinct from parental cells, plays a crucial role in diseases like cancer. However, lipidomic analysis of exosomes, particularly in complex samples like blood, requires advanced techniques. This study optimizes miniaturized flow field-flow fractionation (mFlFFF) coupled with electrospray ionization mass spectrometry (ESI-MS) for direct lipidomic analysis of exosomes in serum. The mFlFFF technique resolves exosomes for size-based lipid analysis without prior extraction. Lipidomic profiling of serum exosomes from patients with extrahepatic cholangiocarcinoma (eCCA) identified over 1000 lipid species, with 64 showing significant changes compared to healthy controls. Target lipids were analyzed by mFlFFF-ESI-MS, revealing 35 species that distinguish eCCA patients from controls, suggesting their potential as biomarkers. Elevated levels of lysophosphatidylcholine, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol (PI) were observed in the eCCA group, indicating lipid alterations linked to cancer progression and inflammation. Notably, PI 38:4, involved in the release of arachidonic acid, highlights its role in inflammatory processes associated with cancer. This study demonstrates the potential of mFlFFF-ESI-MS for lipidomic analysis of exosomes and offers a non-invasive approach for cancer diagnosis, with future implications for therapeutic targeting of lipid pathways in cholangiocarcinoma.
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Affiliation(s)
- Hye Ju Yu
- Department of Chemistry, Yonsei University, Seoul, 03722, South Korea
| | - Myeong Hee Moon
- Department of Chemistry, Yonsei University, Seoul, 03722, South Korea.
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4
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Liu R, Zhang F, He X, Huang K. Plant Derived Exosome-Like Nanoparticles and Their Therapeutic Applications in Glucolipid Metabolism Diseases. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2025; 73:6385-6399. [PMID: 40048449 DOI: 10.1021/acs.jafc.4c12480] [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: 03/20/2025]
Abstract
Plant derived exosome-like nanoparticles (PELNs) are membrane structures isolated from different plants, which encapsulate many active substances such as proteins, lipids, and nucleic acids, which exert a substantial influence on many physiological processes such as plant growth and development, self-defense, and tissue repair. Compared with synthetic nanoparticles and mammalian cell derived exosomes (MDEs), PELNs have lower toxicity and immunogenicity and possess excellent biocompatibility. The intrinsic properties of PELNs establish a robust basis for their applications in the therapeutic management of a diverse array of pathologies. It is worth mentioning that PELNs have good biological targeting, which promotes them to load and deliver drugs to specific tissues, offering a superior development pathway for the construction of a new drug delivery system (DDS). Glucose and lipid metabolism is a vital life process for the body's energy and material supply. The maintenance of homeostatic balance provides a fundamental basis for the body's ability to adjust to modifications in both its internal and external environment. Conversely, homeostatic imbalance can lead to a range of severe metabolic disorders. This work provides a comprehensive overview of the extraction and representation methods of PELNs, their transportation and storage characteristics, and their applications as therapeutic agents for direct treatment and as delivery vehicles to enhance nutrition and health. Additionally, it examines the therapeutic efficacy and practical applications of PELNs in addressing abnormalities in glucose and lipid metabolism. Finally, combined with the above contents, the paper summarizes and provides a conceptual framework for the better application of PELNs in clinical disease treatment.
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Affiliation(s)
- Ruolan Liu
- Key Laboratory of Precision Nutrition and Food Quality, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Feng Zhang
- Key Laboratory of Precision Nutrition and Food Quality, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Xiaoyun He
- Key Laboratory of Precision Nutrition and Food Quality, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
- Key Laboratory of Safety Assessment of Genetically Modified Organism (Food Safety), Ministry of Agriculture and Rural Affairs of the P.R. China, Beijing 100083, China
| | - Kunlun Huang
- Key Laboratory of Precision Nutrition and Food Quality, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
- Key Laboratory of Safety Assessment of Genetically Modified Organism (Food Safety), Ministry of Agriculture and Rural Affairs of the P.R. China, Beijing 100083, China
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5
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An Y, Sun JX, Ma SY, Xu MY, Xu JZ, Liu CQ, Wang SG, Xia QD. From Plant Based Therapy to Plant-Derived Vesicle-Like Nanoparticles for Cancer Treatment: Past, Present and Future. Int J Nanomedicine 2025; 20:3471-3491. [PMID: 40125436 PMCID: PMC11927496 DOI: 10.2147/ijn.s499893] [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: 10/09/2024] [Accepted: 02/21/2025] [Indexed: 03/25/2025] Open
Abstract
Cancer stands as a formidable malady profoundly impacting human health. Throughout history, plant-based therapies have remained pivotal in the arsenal against cancer, evolving alongside the epochs. Presently, challenges such as the arduous extraction of active components and potential safety concerns impede the progression of plant-based anticancer therapies. The isolation of plant-derived vesicle-like nanoparticles (PDVLNs), a kind of lipid bilayer capsules isolated from plants, has brought plant-based anticancer therapy into a novel realm and has led to decades of research on PDVLNs. Accumulating evidence indicates that PDVLNs can deliver plant-derived active substances to human cells and regulate cellular functions. Regulating immunity, inducing cell cycle arrest, and promoting apoptosis in cancer cells are the most commonly reported mechanisms of PDVLNs in tumor suppression. Low immunogenicity and lack of tumorigenicity make PDVLNs a good platform for drug delivery. The molecules within the PDVLNs are all from source plants, so the selection of source plants is crucial. In recent years, there has been a clear trend that the source plants have changed from vegetables or fruits to medicinal plants. This review highlights the mechanisms of medicinal plant-based cancer therapies to identify candidate source plants. More importantly, the current research on PDVLN-based cancer therapy and the applications of PDVLNs for drug delivery are systematically discussed.
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Affiliation(s)
- Ye An
- Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Jian-Xuan Sun
- Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Si-Yang Ma
- Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Meng-Yao Xu
- Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Jin-Zhou Xu
- Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Chen-Qian Liu
- Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Shao-Gang Wang
- Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Qi-Dong Xia
- Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
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6
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Puagsopa J, Tongviseskul N, Jaroentomeechai T, Meksiriporn B. Recent Progress in Developing Extracellular Vesicles as Nanovehicles to Deliver Carbohydrate-Based Therapeutics and Vaccines. Vaccines (Basel) 2025; 13:285. [PMID: 40266147 PMCID: PMC11946770 DOI: 10.3390/vaccines13030285] [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: 01/31/2025] [Revised: 02/22/2025] [Accepted: 03/04/2025] [Indexed: 04/24/2025] Open
Abstract
Cell-derived, nanoscale extracellular vesicles (EVs) have emerged as promising tools in diagnostic, therapeutic, and vaccine applications. Their unique properties including the capability to encapsulate diverse molecular cargo as well as the versatility in surface functionalization make them ideal candidates for safe and effective vehicles to deliver a range of biomolecules including gene editing cassettes, therapeutic proteins, glycans, and glycoconjugate vaccines. In this review, we discuss recent advances in the development of EVs derived from mammalian and bacterial cells for use in a delivery of carbohydrate-based protein therapeutics and vaccines. We highlight key innovations in EVs' molecular design, characterization, and deployment for treating diseases including Alzheimer's disease, infectious diseases, and cancers. We discuss challenges for their clinical translation and provide perspectives for future development of EVs within biopharmaceutical research and the clinical translation landscape.
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Affiliation(s)
- Japigorn Puagsopa
- Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USA;
| | - Niksa Tongviseskul
- Department of Biology, School of Science, King Mongkut’s Institute of Technology Ladkrabang, Bangkok 10520, Thailand;
| | - Thapakorn Jaroentomeechai
- Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark
| | - Bunyarit Meksiriporn
- Department of Biology, School of Science, King Mongkut’s Institute of Technology Ladkrabang, Bangkok 10520, Thailand;
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Wang R, Zhang Y, Guo Y, Zeng W, Li J, Wu J, Li N, Zhu A, Li J, Di L, Cao P. Plant-derived nanovesicles: Promising therapeutics and drug delivery nanoplatforms for brain disorders. FUNDAMENTAL RESEARCH 2025; 5:830-850. [PMID: 40242551 PMCID: PMC11997602 DOI: 10.1016/j.fmre.2023.09.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 08/17/2023] [Accepted: 09/10/2023] [Indexed: 04/18/2025] Open
Abstract
Plant-derived nanovesicles (PDNVs), including plant extracellular vesicles (EVs) and plant exosome-like nanovesicles (ELNs), are natural nano-sized membranous vesicles containing bioactive molecules. PDNVs consist of a bilayer of lipids that can effectively encapsulate hydrophilic and lipophilic drugs, improving drug stability and solubility as well as providing increased bioavailability, reduced systemic toxicity, and enhanced target accumulation. Bioengineering strategies can also be exploited to modify the PDNVs to achieve precise targeting, controlled drug release, and massive production. Meanwhile, they are capable of crossing the blood-brain barrier (BBB) to transport the cargo to the lesion sites without harboring human pathogens, making them excellent therapeutic agents and drug delivery nanoplatform candidates for brain diseases. Herein, this article provides an initial exposition on the fundamental characteristics of PDNVs, including biogenesis, uptake process, isolation, purification, characterization methods, and source. Additionally, it sheds light on the investigation of PDNVs' utilization in brain diseases while also presenting novel perspectives on the obstacles and clinical advancements associated with PDNVs.
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Affiliation(s)
- Ruoning Wang
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
- Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System, Nanjing 210023, China
| | - Yingjie Zhang
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
- Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System, Nanjing 210023, China
| | - Yumiao Guo
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
- Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System, Nanjing 210023, China
| | - Wei Zeng
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
- Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System, Nanjing 210023, China
| | - Jinge Li
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
- Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System, Nanjing 210023, China
| | - Jie Wu
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
- Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System, Nanjing 210023, China
| | - Nengjin Li
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
- Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System, Nanjing 210023, China
| | - Anran Zhu
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
- Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System, Nanjing 210023, China
| | - Jiale Li
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
- Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System, Nanjing 210023, China
| | - Liuqing Di
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
- Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System, Nanjing 210023, China
| | - Peng Cao
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
- Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China
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8
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Yang M, Shi Y, Song Q, Wei Z, Dun X, Wang Z, Wang Z, Qiu CW, Zhang H, Cheng X. Optical sorting: past, present and future. LIGHT, SCIENCE & APPLICATIONS 2025; 14:103. [PMID: 40011460 DOI: 10.1038/s41377-024-01734-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 12/02/2024] [Accepted: 12/24/2024] [Indexed: 02/28/2025]
Abstract
Optical sorting combines optical tweezers with diverse techniques, including optical spectrum, artificial intelligence (AI) and immunoassay, to endow unprecedented capabilities in particle sorting. In comparison to other methods such as microfluidics, acoustics and electrophoresis, optical sorting offers appreciable advantages in nanoscale precision, high resolution, non-invasiveness, and is becoming increasingly indispensable in fields of biophysics, chemistry, and materials science. This review aims to offer a comprehensive overview of the history, development, and perspectives of various optical sorting techniques, categorised as passive and active sorting methods. To begin, we elucidate the fundamental physics and attributes of both conventional and exotic optical forces. We then explore sorting capabilities of active optical sorting, which fuses optical tweezers with a diversity of techniques, including Raman spectroscopy and machine learning. Afterwards, we reveal the essential roles played by deterministic light fields, configured with lens systems or metasurfaces, in the passive sorting of particles based on their varying sizes and shapes, sorting resolutions and speeds. We conclude with our vision of the most promising and futuristic directions, including AI-facilitated ultrafast and bio-morphology-selective sorting. It can be envisioned that optical sorting will inevitably become a revolutionary tool in scientific research and practical biomedical applications.
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Affiliation(s)
- Meng Yang
- Institute of Precision Optical Engineering, School of Physics Science and Engineering, Tongji University, Shanghai, 200092, China
- MOE Key Laboratory of Advanced Micro-Structured Materials, Shanghai, 200092, China
- Shanghai Institute of Intelligent Science and Technology, Tongji University, Shanghai, 200092, China
- Shanghai Frontiers Science Center of Digital Optics, Shanghai, 200092, China
| | - Yuzhi Shi
- Institute of Precision Optical Engineering, School of Physics Science and Engineering, Tongji University, Shanghai, 200092, China.
- MOE Key Laboratory of Advanced Micro-Structured Materials, Shanghai, 200092, China.
- Shanghai Institute of Intelligent Science and Technology, Tongji University, Shanghai, 200092, China.
- Shanghai Frontiers Science Center of Digital Optics, Shanghai, 200092, China.
| | - Qinghua Song
- Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, 518055, China
| | - Zeyong Wei
- Institute of Precision Optical Engineering, School of Physics Science and Engineering, Tongji University, Shanghai, 200092, China
- MOE Key Laboratory of Advanced Micro-Structured Materials, Shanghai, 200092, China
- Shanghai Institute of Intelligent Science and Technology, Tongji University, Shanghai, 200092, China
- Shanghai Frontiers Science Center of Digital Optics, Shanghai, 200092, China
| | - Xiong Dun
- Institute of Precision Optical Engineering, School of Physics Science and Engineering, Tongji University, Shanghai, 200092, China
- MOE Key Laboratory of Advanced Micro-Structured Materials, Shanghai, 200092, China
- Shanghai Institute of Intelligent Science and Technology, Tongji University, Shanghai, 200092, China
- Shanghai Frontiers Science Center of Digital Optics, Shanghai, 200092, China
| | - Zhiming Wang
- Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu, 610054, China
| | - Zhanshan Wang
- Institute of Precision Optical Engineering, School of Physics Science and Engineering, Tongji University, Shanghai, 200092, China
- MOE Key Laboratory of Advanced Micro-Structured Materials, Shanghai, 200092, China
- Shanghai Institute of Intelligent Science and Technology, Tongji University, Shanghai, 200092, China
- Shanghai Frontiers Science Center of Digital Optics, Shanghai, 200092, China
| | - Cheng-Wei Qiu
- Department of Electrical and Computer Engineering, National University of Singapore, Singapore, 117583, Singapore.
| | - Hui Zhang
- Institute of Precision Optical Engineering, School of Physics Science and Engineering, Tongji University, Shanghai, 200092, China.
- MOE Key Laboratory of Advanced Micro-Structured Materials, Shanghai, 200092, China.
- Shanghai Institute of Intelligent Science and Technology, Tongji University, Shanghai, 200092, China.
- Shanghai Frontiers Science Center of Digital Optics, Shanghai, 200092, China.
| | - Xinbin Cheng
- Institute of Precision Optical Engineering, School of Physics Science and Engineering, Tongji University, Shanghai, 200092, China.
- MOE Key Laboratory of Advanced Micro-Structured Materials, Shanghai, 200092, China.
- Shanghai Institute of Intelligent Science and Technology, Tongji University, Shanghai, 200092, China.
- Shanghai Frontiers Science Center of Digital Optics, Shanghai, 200092, China.
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Plavchak CL, Liu J, Wang Y, Xu X, Faustino PJ, Qu H, Smith WC. Utilization of AF4 for characterizing complex nanomaterial drug products: Reexamining sample recovery and its impact on particle size distribution as a quality attribute. J Chromatogr A 2025; 1743:465703. [PMID: 39874741 DOI: 10.1016/j.chroma.2025.465703] [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: 07/31/2024] [Revised: 01/10/2025] [Accepted: 01/20/2025] [Indexed: 01/30/2025]
Abstract
Asymmetrical flow field-flow fractionation (AF4) with multi-detection has continued to gain wider acceptance for characterizing complex drug products. An important quality attribute for these products is the measurement of the particle size distribution (PSD). Current limitations of established procedures (e.g., dynamic light scattering) for accurately determining PSD can be overcome by AF4. However, while gaining acceptance this technique has not been fully adopted within the pharmaceutical industry. A technical understanding of fundamental operational factors is necessary for the successful application of utilizing any emerging technology. For example, recovery (R% = AS/AD*100, where AS and AD are the peak areas from the concentration detector with and without the crossflow field, respectively) is one factor that is used to assess the robustness during AF4 method development, but currently little is known about the interplay between analyte recovery and PSD. This work highlights factors that impact calculated AF4 recovery, and how differences in analyte and absolute recovery ultimately influence the PSD of nanoparticle size standards and complex drug product formulations such as emulsions and liposomes. Factors like ionic strength, buffer composition, and analyte chemistries, which are the most common factors associated with changes to R% in AF4, contributed to changes in AS. While AD is not typically examined in detail, the selection of the concentration detector (UV or dRI) along with their instrumental parameters (e.g., wavelength, attenuation value, linear range) and sample preparation was shown to under- or over-estimate AD thus changing R%. Examining both components of R% and their contributions to analyte and absolute recovery show that decreases in analyte recovery may not be exclusively due to sample loss but could be influenced by changes in analyte-membrane interactions or analyte instability. Because of this, four relationships between recovery and PSD were defined. While R% is used as a tool for assessing AF4 methodology, the factors investigated through this work warrant further considerations when establishing an appropriate R% threshold.
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Affiliation(s)
- Christine L Plavchak
- Office of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993, USA
| | - Joanne Liu
- Office of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993, USA
| | - Yan Wang
- Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA
| | - Xiaoming Xu
- Office of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993, USA
| | - Patrick J Faustino
- Office of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993, USA
| | - Haiou Qu
- Office of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993, USA.
| | - William C Smith
- Office of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993, USA.
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10
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Zhao X, Wei Y, Bu Y, Ren X, Dong Z. Review on bacterial outer membrane vesicles: structure, vesicle formation, separation and biotechnological applications. Microb Cell Fact 2025; 24:27. [PMID: 39833809 PMCID: PMC11749425 DOI: 10.1186/s12934-025-02653-9] [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: 10/19/2024] [Accepted: 01/13/2025] [Indexed: 01/22/2025] Open
Abstract
Outer membrane vesicles (OMVs), shed by Gram-negative bacteria, are spherical nanostructures that play a pivotal role in bacterial communication and host-pathogen interactions. Comprising an outer membrane envelope and encapsulating a variety of bioactive molecules from their progenitor bacteria, OMVs facilitate material and informational exchange. This review delves into the recent advancements in OMV research, providing a comprehensive overview of their structure, biogenesis, and mechanisms of vesicle formation. It also explores their role in pathogenicity and the techniques for their enrichment and isolation. Furthermore, the review highlights the burgeoning applications of OMVs in the field of biomedicine, emphasizing their potential as diagnostic tools, vaccine candidates, and drug delivery vectors.
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Affiliation(s)
- Xiaofei Zhao
- Graduate School, Hebei Medical University, Shijiazhuang, China
- Department of Pharmacy, Hebei Key Laboratory of Clinical Pharmacy, Hebei General Hospital, Shijiazhuang, China
| | - Yusen Wei
- Department of Oncology, Hebei General Hospital, Shijiazhuang, China
| | - Yuqing Bu
- Department of Oncology, Hebei General Hospital, Shijiazhuang, China
| | - Xiaokai Ren
- Graduate School, Hebei Medical University, Shijiazhuang, China
- Department of Pharmacy, Hebei Key Laboratory of Clinical Pharmacy, Hebei General Hospital, Shijiazhuang, China
| | - Zhanjun Dong
- Graduate School, Hebei Medical University, Shijiazhuang, China.
- Department of Pharmacy, Hebei Key Laboratory of Clinical Pharmacy, Hebei General Hospital, Shijiazhuang, China.
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11
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Lin F, Luo H, Wang J, Li Q, Zha L. Macrophage-derived extracellular vesicles as new players in chronic non-communicable diseases. Front Immunol 2025; 15:1479330. [PMID: 39896803 PMCID: PMC11782043 DOI: 10.3389/fimmu.2024.1479330] [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: 08/13/2024] [Accepted: 12/23/2024] [Indexed: 02/04/2025] Open
Abstract
Macrophages are innate immune cells present in all tissues and play an important role in almost all aspects of the biology of living organisms. Extracellular vesicles (EVs) are released by cells and transport their contents (micro RNAs, mRNA, proteins, and long noncoding RNAs) to nearby or distant cells for cell-to-cell communication. Numerous studies have shown that macrophage-derived extracellular vesicles (M-EVs) and their contents play an important role in a variety of diseases and show great potential as biomarkers, therapeutics, and drug delivery vehicles for diseases. This article reviews the biological functions and mechanisms of M-EVs and their contents in chronic non-communicable diseases such as cardiovascular diseases, metabolic diseases, cancer, inflammatory diseases and bone-related diseases. In addition, the potential application of M-EVs as drug delivery systems for various diseases have been summarized.
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Affiliation(s)
- Fengjuan Lin
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
| | - Huiyu Luo
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
| | - Jiexian Wang
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
| | - Qing Li
- Department of Clinical Nutrition, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Longying Zha
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
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12
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Das A, Sonar S, Kalele K, Subramaniyan V. Fruit exosomes: a sustainable green cancer therapeutic. SUSTAINABLE FOOD TECHNOLOGY 2025; 3:145-160. [DOI: 10.1039/d4fb00281d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/27/2024]
Abstract
Fruit exosomes are the source of natural cancer therapeutic tools.
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Affiliation(s)
- Asmit Das
- Center for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, India
| | - Swarup Sonar
- Center for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, India
| | - Ketki Kalele
- Department of Oncology, Neuron Institute of Applied Research, Amravati, Maharashtra, India
| | - Vetriselvan Subramaniyan
- Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, 47500 Subang Jaya, Selangor, Malaysia
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13
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Zhang J, Pang H, Tang H, Tu Q, Xia F, Zhang H, Meng Y, Han G, Wang J, Qiu C. The pharmacodynamic and pharmacological mechanisms underlying nanovesicles of natural products: Developments and challenges. Pharmacol Ther 2025; 265:108754. [PMID: 39566562 DOI: 10.1016/j.pharmthera.2024.108754] [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: 02/29/2024] [Revised: 10/23/2024] [Accepted: 11/15/2024] [Indexed: 11/22/2024]
Abstract
Natural products such as Traditional Chinese Medicines (TCMs) show great advantages in the treatment and prevention of diseases, but the unclear effective ingredients and mechanisms are key obstacles to restrict their rapid development. Under the guidance of the theoretical guidance of reductionism and the theoretical of allopathic medicine, some researches have indeed achieved some breakthrough results. However, these incomplete methods mainly limited to direct actions or indirect actions (such as the intermediated substances mediated cross-organ or cross-system regulation) mechanism of single active ingredient derived from natural products, which are often inconsistent with Systemism and Harmonizing Medicine and make it difficult to reasonably explain the pharmacodynamics and pharmacological mechanism of most natural products. Actually, effective pharmaceutical ingredients often do not exist in the form of free monomers, but prefer to assembly nanovesicles (NVs) for a combinational pharmacological effect, mainly including self-assembled nanoparticles (SANs) and exosome-like nanoparticles (ELNs). These developments of NVs-based application are a good supplement to existing pharmacological mechanism research. Hence, this review focuses on the developments and strategies of the pharmacodynamics and pharmacological mechanism of NVs-based TCMs under the combining theory of traditional Chinese and western medicine. On this basis, a novel "multidimensional combination" research approach is proposed firstly, which will provide new strategies and directions for breaking through the bottleneck of pharmacological mechanism research, and promote the clinical application of innovative natural products including TCMs.
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Affiliation(s)
- Junzhe Zhang
- State Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng 475004, China; State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Huanhuan Pang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Huan Tang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Qingchao Tu
- State Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng 475004, China; State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Fei Xia
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Hao Zhang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Yuqing Meng
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Guang Han
- State Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng 475004, China.
| | - Jigang Wang
- State Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng 475004, China; State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; Department of Biological Sciences, National University of Singapore, Singapore 119077, Singapore.
| | - Chong Qiu
- State Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng 475004, China; State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
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14
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Thakur A, Rai D. Global requirements for manufacturing and validation of clinical grade extracellular vesicles. THE JOURNAL OF LIQUID BIOPSY 2024; 6:100278. [PMID: 40027307 PMCID: PMC11863704 DOI: 10.1016/j.jlb.2024.100278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Revised: 11/17/2024] [Accepted: 11/18/2024] [Indexed: 03/05/2025]
Abstract
Extracellular vesicles (EVs) are nanovesicles released from different cell types from biofluids such as blood, urine, and cerebrospinal fluid. They vary in size and biomarkers, and their biogenesis pathways allow them to be divided into three major types: exosomes, micro-vesicles, and apoptotic bodies. EVs have been studied in the context of diagnosis and therapeutic intervention of various pathological conditions such as cancer, neurodegenerative diseases, and pulmonary diseases. However, the production of EV-based therapeutics can be affected by the source, heterogeneity, or disease, raising questions about the manufacturing and validation of EVs of clinical grade and their scope regarding good manufacturing practice (GMP) in the industry. To address this, we have discussed the state-of-the-art requirements for EV production that must occur in a GMP-compliant environment with a reliable and traceable source. Additionally, EVs' homogeneity and the therapeutics' purity and stability must be analyzed and validated. Quality control measures must also be established to ensure the safety and efficacy of EVs. In conclusion, these considerations must be weighed carefully when manufacturing and validating EVs of clinical grade to ensure their safety and efficacy for therapeutic use.
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Affiliation(s)
- Abhimanyu Thakur
- Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Deepika Rai
- Smidt Heart Institute, Cedars-Sinai Medical Centre, Los Angeles, CA, United States
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15
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Dilsiz N. A comprehensive review on recent advances in exosome isolation and characterization: Toward clinical applications. Transl Oncol 2024; 50:102121. [PMID: 39278189 PMCID: PMC11418158 DOI: 10.1016/j.tranon.2024.102121] [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: 05/04/2024] [Revised: 09/03/2024] [Accepted: 09/11/2024] [Indexed: 09/18/2024] Open
Abstract
Exosomes are small, round vesicles in the 30 and 120 nm diameter range released by all living cell types. Exosomes play many essential functions in intercellular communication and tissue crosstalk in the human body. They can potentially be used as strong biomarkers and therapeutic agents for early diagnosis, therapy response, and prognosis of different diseases. The main requirements for exosomal large-scale clinical practice application are rapid, easy, high-yield, high purity, characterization, safety, low cost, and therapeutic efficacy. Depending on the sample types, environmental insults, and exosome quantity, exosomes can be isolated from various sources, including body fluids, solid tissues, and cell culture medium using different procedures. This study comprehensively analyzed the current research progress in exosome isolation and characterization strategies along with their advantages and disadvantages. The provided information will make it easier to select exosome separation methods based on the types of biological samples available, and it will facilitate the use of exosomes in translational and clinical research, particularly in cancer. Lay abstract Exosomes have recently received much attention due to their potential to function as biomarkers and novel therapeutic agents for early diagnosis, therapeutic response, and prognosis in various diseases. This review summarizes many approaches for isolating and characterizing exosomes, focusing on developing technologies, and provides an in-depth comparison and analysis of each method, including its principles, advantages, and limitations.
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Affiliation(s)
- Nihat Dilsiz
- Experimental Medicine Application and Research Center (EMARC) Validebag Research Park, University of Health Sciences, Istanbul, Turkey.
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16
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Jeppesen DK, Zhang Q, Coffey RJ. Extracellular vesicles and nanoparticles at a glance. J Cell Sci 2024; 137:jcs260201. [PMID: 39641198 DOI: 10.1242/jcs.260201] [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] [Indexed: 12/07/2024] Open
Abstract
Cells can communicate with neighboring and more distant cells by secretion of extracellular vesicles (EVs). EVs are lipid bilayer membrane-bound structures that can be packaged with proteins, nucleic acids and lipids that mediate cell-cell signaling. EVs are increasingly recognized to play numerous important roles in both normal physiological processes and pathological conditions. Steady progress in the field has uncovered a great diversity and heterogeneity of distinct vesicle types that appear to be secreted from most, if not all, cell types. Recently, it has become apparent that cells also release non-vesicular extracellular nanoparticles (NVEPs), including the newly discovered exomeres and supermeres. In this Cell Science at a Glance article and the accompanying poster, we provide an overview of the diversity of EVs and nanoparticles that are released from cells into the extracellular space, highlighting recent advances in the field.
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Affiliation(s)
- Dennis K Jeppesen
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Qin Zhang
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Robert J Coffey
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
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17
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Meng K, Meng F, Wu Y, Lin L. Multi-omics analysis identified extracellular vesicles as biomarkers for cardiovascular diseases. Talanta 2024; 280:126710. [PMID: 39213888 DOI: 10.1016/j.talanta.2024.126710] [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: 05/07/2024] [Revised: 08/09/2024] [Accepted: 08/13/2024] [Indexed: 09/04/2024]
Abstract
Cell-derived extracellular vesicles (EVs) have emerged as a promising non-invasive liquid biopsy technique due to their accessibility and their ability to encapsulate and transport diverse biomolecules. EVs have garnered substantial research interest, notably in cardiovascular diseases (CVDs), where their roles in pathophysiology and as diagnostic and prognostic biomarkers are increasingly recognized. This review provides a comprehensive overview of EVs, starting with their origins, followed by the techniques used for their isolation and characterization. We explore the diverse cargo of EVs, including nucleic acids, proteins, lipids, and metabolites, highlighting their roles in intercellular communication and as potential biomarkers. We then delve into the application of genomics, transcriptomics, proteomics, and metabolomics in the analysis of EVs, particularly within the context of CVDs. Finally, we discuss how integrated multi-omics approaches are unveiling novel biomarkers, offering fresh insights into the diagnosis and prognosis of CVDs. This review underscores the growing importance of EVs in clinical diagnostics and the potential of multi-omics to propel future advancements in CVD biomarker discovery.
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Affiliation(s)
- Ke Meng
- Medical College, Guangxi University, Nanning, Guangxi, China
| | - Fanqi Meng
- Xiamen Cardiovascular Hospital, Xiamen University, Xiamen, 361004, Fujian, China
| | - Yuan Wu
- Department of Cardiac Surgery, Yuebei People's Hospital, Shaoguan, Guangdong, China.
| | - Ling Lin
- Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
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18
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Nishimura H, Hashii N, Yamamoto T, Sun Y, Miura T, Sato Y, Ishii-Watabe A. Usefulness of Size-Exclusion Chromatography-Multi-Angle Light Scattering to Assess Particle Composition and Protein Impurities for Quality Control of Therapeutic Exosome Preparations. Pharmaceutics 2024; 16:1526. [PMID: 39771505 PMCID: PMC11728667 DOI: 10.3390/pharmaceutics16121526] [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: 10/30/2024] [Revised: 11/20/2024] [Accepted: 11/21/2024] [Indexed: 01/16/2025] Open
Abstract
Background: Extracellular vesicles (EVs), including exosomes, are promising pharmaceutical modalities. They are purified from cell culture supernatant; however, the preparation may contain EVs with the desired therapeutic effects and different types of EVs, lipoproteins, and soluble proteins. Evaluating the composition of particulate impurities and the levels of protein impurities in final preparations is critical for quality control. However, few analytical methods can detect these impurities. Methods: We established and evaluated an analytical method using size-exclusion chromatography-multi-angle light scattering (SEC-MALS) for particle and protein impurity analyses of EV samples. Results: In the particle size distribution analysis of EV samples, SEC-MALS showed higher resolution compared with nanoparticle tracking analysis (NTA) and dynamic light scattering (DLS). MALS showed comparable accuracy and precision to that of other methods for particle size evaluation using polystyrene standard beads with 60, 100, or 200 nm diameter. Coupling SEC-MALS with UV detection quantitatively evaluated soluble protein impurities. Proteomic analysis on the SEC-MALS-fractionated samples identified different EV and lipoprotein marker proteins in different fractions. Conclusions: SEC-MALS can characterize EV preparations obtained from human adipose-derived mesenchymal stem cells, suggesting that it can evaluate the particle component composition in various EV samples and therapeutic exosome preparations.
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Affiliation(s)
- Hirotaka Nishimura
- Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki 210-9501, Kanagawa, Japan; (H.N.)
| | - Noritaka Hashii
- Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki 210-9501, Kanagawa, Japan; (H.N.)
| | - Tomofumi Yamamoto
- Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki 210-9501, Kanagawa, Japan; (H.N.)
| | - Yuchen Sun
- Division of Medicinal Safety Science, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki 210-9501, Kanagawa, Japan
| | - Takumi Miura
- Division of Cell-Based Therapeutic Products, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki 210-9501, Kanagawa, Japan
| | - Yoji Sato
- Division of Drugs, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki 210-9501, Kanagawa, Japan
| | - Akiko Ishii-Watabe
- Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki 210-9501, Kanagawa, Japan; (H.N.)
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19
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Zhang J, Tian S, Guo L, Zhao H, Mao Z, Miao M. Chinese herbal medicine-derived extracellular vesicles as novel biotherapeutic tools: present and future. J Transl Med 2024; 22:1059. [PMID: 39587576 PMCID: PMC11587639 DOI: 10.1186/s12967-024-05892-3] [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: 07/10/2024] [Accepted: 11/14/2024] [Indexed: 11/27/2024] Open
Abstract
Extracellular vesicles (EVs) are phospholipid bilayer-enclosed biological particles that are secreted by almost all living cells including animals, plants, and microorganisms. Chinese herbal medicines (CHM) have a long history of using plant-based remedies to treat and prevent human diseases. Chinese herbal medicine-derived extracellular vesicle (CHMEV) generic term refers to nanoscale membrane structures isolated from medicinal plants such as ginseng, ginger, and Panax notoginseng. In recent years, CHMEVs have garnered substantial attention as a novel class of functional components due to their high bioavailability, safety, easy accessibility, and diverse therapeutic effects, indicating their great potential for development as a new dosage form of CHM. Research on CHMEVs in traditional Chinese medicine (TCM) has become a prominent area of interest, opening new avenues for further exploration into the therapeutic effects and functional mechanisms of CHM. Nonetheless, as an emerging field, there is much unknown about these vesicles, and current research remains inconsistent. The review comprehensively summarizes the biogenesis, isolation methods, and physical, and biochemical characterizations of CHMEVs. Additionally, we highlight their biomedical applications as therapeutic agents and drug delivery carriers, including anti-inflammatory, anticancer, regenerative, and antiaging activities. Finally, we propose current challenges and future perspectives. By summarizing the existing literature, we aim to offer valuable clues and inspiration for future CHMEV research, thereby facilitating research standardization of CHMEVs in the treatment of human diseases and drug discovery.
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Affiliation(s)
- Jinying Zhang
- Academy of Traditional Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, 450046, Henan Province, PR China
| | - Shuo Tian
- Academy of Traditional Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, 450046, Henan Province, PR China
- Henan Collaborative Innovation Center for Research and Development on the Whole Industry Chain of Yu- Yao Affiliated to Henan University of Chinese Medicine, Zhengzhou, 450046, Henan Province, PR China
| | - Lin Guo
- Academy of Traditional Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, 450046, Henan Province, PR China
| | - Hui Zhao
- Academy of Traditional Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, 450046, Henan Province, PR China
| | - Zhiguo Mao
- Academy of Traditional Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, 450046, Henan Province, PR China
| | - Mingsan Miao
- Academy of Traditional Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, 450046, Henan Province, PR China.
- Henan Collaborative Innovation Center for Research and Development on the Whole Industry Chain of Yu- Yao Affiliated to Henan University of Chinese Medicine, Zhengzhou, 450046, Henan Province, PR China.
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20
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Zeng YB, Deng X, Shen LS, Yang Y, Zhou X, Ye L, Chen S, Yang DJ, Chen GQ. Advances in plant-derived extracellular vesicles: isolation, composition, and biological functions. Food Funct 2024; 15:11319-11341. [PMID: 39523827 DOI: 10.1039/d4fo04321a] [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: 11/16/2024]
Abstract
Plant-derived extracellular vesicles (PDEVs) are nanoscale vesicles released from plant cells into the extracellular space. While similar in structure and function to mammalian-derived EVs, PDEVs are unique due to their origin and the specific metabolites they carry. PDEVs have gained significant attention in recent years, with numerous reports isolating different PDEVs from various plants, each exhibiting diverse biological functions. However, the field is still in its early stages, and many issues need further exploration. To better develop and utilize PDEVs, it is essential to have a comprehensive understanding of their characteristics. This review provides an overview of recent advances in PDEV research. It focuses on the methods and techniques for isolating and purifying PDEVs, comparing their respective advantages, limitations, and application scenarios. Furthermore, we discuss the latest discoveries regarding the composition of PDEVs, including lipids, proteins, nucleic acids, and various plant metabolites. Additionally, we detail advanced studies on the multiple biological functions of PDEVs. Our goal is to advance our understanding of PDEVs and encourage further exploration in PDEV-based science and technology, offering insights into their potential applications for human health.
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Affiliation(s)
- Yao-Bo Zeng
- Department of Chinese Materia Medica, Chongqing University of Chinese Medicine, Chongqing 402760, China
- College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
| | - Xun Deng
- School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, China
- State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518057, China.
| | - Li-Sha Shen
- Chongqing Academy of Chinese Materia Medica, Chongqing 400065, China.
- Sichuan-Chongqing Joint Key Laboratory of Innovation of New Drugs of Traditional Chinese Medicine, Chongqing 400065, China
| | - Yong Yang
- Chongqing Academy of Chinese Materia Medica, Chongqing 400065, China.
- Sichuan-Chongqing Joint Key Laboratory of Innovation of New Drugs of Traditional Chinese Medicine, Chongqing 400065, China
| | - Xing Zhou
- Department of Chinese Materia Medica, Chongqing University of Chinese Medicine, Chongqing 402760, China
| | - Lianbao Ye
- School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, China
| | - Sibao Chen
- State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518057, China.
- Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hung Hom, Hong Kong S.A.R., China
- Research Centre for Chinese Medicine Innovation, The Hong Kong Polytechnic University, Hung Hom, Hong Kong S.A.R., China
| | - Da-Jian Yang
- Chongqing Academy of Chinese Materia Medica, Chongqing 400065, China.
- Sichuan-Chongqing Joint Key Laboratory of Innovation of New Drugs of Traditional Chinese Medicine, Chongqing 400065, China
| | - Guo-Qing Chen
- State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518057, China.
- Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hung Hom, Hong Kong S.A.R., China
- Research Centre for Chinese Medicine Innovation, The Hong Kong Polytechnic University, Hung Hom, Hong Kong S.A.R., China
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21
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Plavchak CL, Werner AZ, Betz E, Salvachúa D, Beckham GT, Kim Ratanathanawongs Williams S. Determination of particle number concentration for biological particles using AF4-MALS: Dependencies on light scattering model and refractive index. J Chromatogr A 2024; 1737:465460. [PMID: 39476775 DOI: 10.1016/j.chroma.2024.465460] [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: 09/16/2024] [Revised: 10/17/2024] [Accepted: 10/18/2024] [Indexed: 11/10/2024]
Abstract
Determining accurate counts and size distributions for biological particles (bioparticles) is crucial in wide-ranging fields, but current methods to this end are susceptible to bias from polydispersity in size. This bias can be mitigated by incorporating a separation step prior to characterization. For this reason, asymmetrical flow field-flow fractionation (AF4) with on-line multiangle light scattering (MALS) has become an important platform for determining particle size. AF4-MALS has also been increasingly used to report particle concentration, particularly for complex biological particles, yet the impact of light scattering models and particle refractive indices (RI) have not been quantitatively evaluated. Here, we develop an analysis workflow using AF4-MALS to simultaneously separate and determine particles sizes and concentrations. The impacts of the MALS particle counting model used to process data and the chosen RI value(s) on particle counts are systematically assessed for polystyrene latex (PSL) particles and bacterial outer membrane vesicles (OMVs) in the 20-500 nm size range. Across spherical models, PSL and OMV particle counts varied up to 13 % or 200 %, respectively. For the coated-sphere model used in the analysis of OMV samples, the sphere RI value greatly impacts particle counts. As the sphere RI value approaches the RI of the suspending medium, the model becomes increasingly sensitive to the light scattering signal-to-noise ratio ultimately causing erroneous particle counts. Overall, this work establishes the importance of selecting appropriate MALS models and RI values for bioparticles to obtain accurate counts and provides an AF4-MALS method to separate, enumerate, and size polydisperse bioparticles.
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Affiliation(s)
- Christine L Plavchak
- Department of Chemistry, Colorado School of Mines, 1500 Illinois St., Golden, CO 80401, United States
| | - Allison Z Werner
- Renewable Resources and Enabling Sciences Center, National Renewable Energy Laboratory, Golden, CO 80401, United States
| | - Elizabeth Betz
- Department of Chemistry, Colorado School of Mines, 1500 Illinois St., Golden, CO 80401, United States
| | - Davinia Salvachúa
- Renewable Resources and Enabling Sciences Center, National Renewable Energy Laboratory, Golden, CO 80401, United States
| | - Gregg T Beckham
- Renewable Resources and Enabling Sciences Center, National Renewable Energy Laboratory, Golden, CO 80401, United States
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22
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Bin Islam MK, Marcus RK. Isolation and quantification of human urinary exosomes using a Tween-20 elution solvent from polyester, capillary-channeled polymer fiber columns. Anal Chim Acta 2024; 1329:343242. [PMID: 39396305 PMCID: PMC11471952 DOI: 10.1016/j.aca.2024.343242] [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: 03/13/2024] [Revised: 08/08/2024] [Accepted: 09/11/2024] [Indexed: 10/15/2024]
Abstract
BACKGROUND Exosomes, a subset of extracellular vesicles (EVs), are a type of membrane-secreted vesicle essential for intercellular communication. There is a great deal of interest in developing methods to isolate and quantify exosomes to study their role in intercellular processes and as potential therapeutic delivery systems. Polyester, capillary-channeled polymer fiber columns and spin-down tips are highly efficient, low-cost means of exosome isolation. As the methodology evolves, there remain questions as to the optimum elution solvent for specific end-uses of the recovered vesicles; fundamental biochemistry, clinical diagnostics, or therapeutic vectors. RESULTS While both acetonitrile and glycerol have been proven highly successful in terms of EV recoveries in the hydrophobic interaction chromatography workflow, many biological studies entail the use of the non-ionic detergent, Tween-20, as a working solvent. Here we evaluate the use of Tween-20 as the elution solvent for the recovery of exosomes. A novel 10-min, two-step gradient elution method, employing 0.1 % v/v Tween-20, efficiently isolated EVs at a concentration of ∼1011 EV mL-1 from a 100 μL urine injection. Integration of absorbance and multi-angle light scattering detectors in standard HPLC instrumentation enables a comprehensive single-injection determination of eluted exosome concentration and sizes. Transmission electron microscopy verifies the retention of the vesicular structure of the exosomes. The micro-bicinchoninic acid protein quantification assay confirmed high-purity isolations of exosomes (∼99 % removal of background proteins) SIGNIFICANCE: The effective use of Tween-20 as an elution solvent for exosome isolation/purification using capillary-channeled polymer fiber columns adds greater versatility to the portfolio of the approach. The proposed method holds promise for a wide range of fundamental biochemistry, clinical diagnostics, and therapeutic applications, marking a significant advancement in EV-based methodologies.
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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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Tang H, Yu D, Zhang J, Wang M, Fu M, Qian Y, Zhang X, Ji R, Gu J, Zhang X. The new advance of exosome-based liquid biopsy for cancer diagnosis. J Nanobiotechnology 2024; 22:610. [PMID: 39380060 PMCID: PMC11463159 DOI: 10.1186/s12951-024-02863-0] [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: 01/16/2024] [Accepted: 09/16/2024] [Indexed: 10/10/2024] Open
Abstract
Liquid biopsy is a minimally invasive method that uses biofluid samples instead of tissue samples for cancer diagnosis. Exosomes are small extracellular vesicles secreted by donor cells and act as mediators of intercellular communication in human health and disease. Due to their important roles, exosomes have been considered as promising biomarkers for liquid biopsy. However, traditional methods for exosome isolation and cargo detection methods are time-consuming and inefficient, limiting their practical application. In the past decades, many new strategies, such as microfluidic chips, nanowire arrays and electrochemical biosensors, have been proposed to achieve rapid, accurate and high-throughput detection and analysis of exosomes. In this review, we discussed about the new advance in exosome-based liquid biopsy technology, including isolation, enrichment, cargo detection and analysis approaches. The comparison of currently available methods is also included. Finally, we summarized the advantages and limitations of the present strategies and further gave a perspective to their future translational use.
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Affiliation(s)
- Haozhou Tang
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, China
- Department of Orthopaedics, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, Jiangsu, 215300, China
| | - Dan Yu
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, China
| | - Jiahui Zhang
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, China
| | - Maoye Wang
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, China
| | - Min Fu
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, China
| | - Yu Qian
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, China
| | - Xiaoxin Zhang
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, China
| | - Runbi Ji
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, China
| | - Jianmei Gu
- Departmemt of Clinical Laboratory Medicine, Nantong Tumor Hospital/Affiliated Tumor Hospital of Nantong University, Nantong, 226300, China.
- Affiliated Cancer Hospital of Nantong University, Nantong, 226300, China.
| | - Xu Zhang
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, China.
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Sani F, Shafiei F, Dehghani F, Mohammadi Y, Khorraminejad‐Shirazi M, Anvari‐Yazdi AF, Moayedfard Z, Azarpira N, Sani M. Unveiling exosomes: Cutting-edge isolation techniques and their therapeutic potential. J Cell Mol Med 2024; 28:e70139. [PMID: 39431552 PMCID: PMC11492151 DOI: 10.1111/jcmm.70139] [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: 06/16/2024] [Revised: 09/12/2024] [Accepted: 10/01/2024] [Indexed: 10/22/2024] Open
Abstract
Exosomes are one type of nanosized membrane vesicles with an endocytic origin. They are secreted by almost all cell types and play diverse functional roles. It is essential for research purposes to differentiate exosomes from microvesicles and isolate them from other components in a fluid sample or cell culture medium. Exosomes are important mediators in cell-cell communication. They deliver their cargos, such as mRNA transcripts, microRNA, lipids, cytosolic and membrane proteins and enzymes, to target cells with or without physical connections between cells. They are highly heterogeneous in size, and their biological functions can vary depending on the cell type, their ability to interact with recipient cells and transport their contents, and the environment in which they are produced. This review summarized the recent progress in exosome isolation and characterization techniques. Moreover, we review the therapeutic approaches, biological functions of exosomes in disease progression, tumour metastasis regulation, immune regulation and some ongoing clinical trials.
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Affiliation(s)
- Farnaz Sani
- Shiraz Institute for Stem Cell & Regenerative MedicineShiraz University of Medical SciencesShirazIran
| | - Faezeh Shafiei
- Shiraz Institute for Stem Cell & Regenerative MedicineShiraz University of Medical SciencesShirazIran
| | - Farshad Dehghani
- Shiraz Institute for Stem Cell & Regenerative MedicineShiraz University of Medical SciencesShirazIran
| | - Yasaman Mohammadi
- Pharmaceutical Sciences Research CenterShiraz University of Medical ScienceShirazIran
| | - Mohammadhossein Khorraminejad‐Shirazi
- Department of Pathology, School of MedicineShiraz University of Medical SciencesShirazIran
- Student Research CommitteeShiraz University of Medical SciencesShirazIran
- Department of Pathology, School of MedicineJahrom University of Medical SciencesJahromIran
| | | | - Zahra Moayedfard
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Medical Sciences and TechnologiesShiraz University of Medical SciencesShirazIran
| | - Negar Azarpira
- Shiraz Institute for Stem Cell & Regenerative MedicineShiraz University of Medical SciencesShirazIran
- Transplant Research CenterShiraz University of Medical SciencesShirazIran
| | - Mahsa Sani
- Shiraz Institute for Stem Cell & Regenerative MedicineShiraz University of Medical SciencesShirazIran
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Medical Sciences and TechnologiesShiraz University of Medical SciencesShirazIran
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25
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Gao Z, Lin J, Su WC, Zhang K, Gruenhagen J, Zhong W, Fan Y, Bian J. Development of an advanced separation and characterization platform for mRNA and lipid nanoparticles using multi-detector asymmetrical flow field-flow fractionation. Anal Bioanal Chem 2024; 416:5281-5293. [PMID: 39102094 DOI: 10.1007/s00216-024-05455-x] [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: 06/01/2024] [Revised: 07/11/2024] [Accepted: 07/16/2024] [Indexed: 08/06/2024]
Abstract
In recent years, the use of lipid nanoparticles (LNPs) for delivery of messenger RNA (mRNA)-based therapies has gained substantial attention in the field of drug development. In such an application, multiple LNP attributes have to be carefully characterized to ensure product safety and quality, whereas accurate and efficient characterization of these complex mRNA-LNP formulations remains a challenging endeavor. Here, we present the development and application of an online separation and characterization platform designed for the isolation and in-depth analysis of mRNAs and mRNA-loaded LNPs. Our asymmetrical flow field-flow fractionation with a multi-detector (MD-AF4) method has demonstrated exceptional resolution between mRNA-LNPs and mRNAs, delivering excellent recoveries (over 70%) for both analytes and exceptional repeatability. Notably, this platform allows for comprehensive and multi-attribute LNP characterization, including online particle sizing, morphology characterization, and determination of encapsulation efficiency, all within a single injection. Furthermore, real-time online sizing by synchronizing multi-angle light scattering (MALS) and dynamic light scattering (DLS) presented higher resolution over traditional batch-mode DLS, particularly in differentiating heterogeneous samples with a low abundance of large-sized particles. Additionally, our method proves to be a valuable tool for monitoring LNP stability under varying stress conditions. Our work introduces a robust and versatile analytical platform using MD-AF4 that not only efficiently provides multi-attribute characterizations of mRNA-LNPs but also holds promise in advancing studies related to formulation screening, quality control, and stability assessment in the evolving field of nanoparticle delivery systems for mRNAs.
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Affiliation(s)
- Ziting Gao
- Department of Chemistry, University of California, Riverside, 900 University Ave., Riverside, CA, 92521, USA
| | - Jessica Lin
- Genentech Research and Early Development, Genentech Inc., 1 DNA Way, South San Francisco, CA, 94080, USA
| | - Wan-Chih Su
- Genentech Research and Early Development, Genentech Inc., 1 DNA Way, South San Francisco, CA, 94080, USA
| | - Kelly Zhang
- Genentech Research and Early Development, Genentech Inc., 1 DNA Way, South San Francisco, CA, 94080, USA
| | - Jason Gruenhagen
- Genentech Research and Early Development, Genentech Inc., 1 DNA Way, South San Francisco, CA, 94080, USA
| | - Wenwan Zhong
- Department of Chemistry, University of California, Riverside, 900 University Ave., Riverside, CA, 92521, USA
| | - Yuchen Fan
- Genentech Research and Early Development, Genentech Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.
| | - Juan Bian
- Genentech Research and Early Development, Genentech Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.
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26
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De Giorgis V, Barberis E, Manfredi M. Extracellular vesicles proteins for early cancer diagnosis: From omics to biomarkers. Semin Cancer Biol 2024; 104-105:18-31. [PMID: 39074601 DOI: 10.1016/j.semcancer.2024.07.003] [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: 04/25/2024] [Revised: 07/23/2024] [Accepted: 07/24/2024] [Indexed: 07/31/2024]
Abstract
Extracellular vesicles (EVs) are a promising source of early biomarkers for cancer diagnosis. They are enriched with diverse molecular content, such as proteins, DNA, mRNA, miRNA, lipids, and metabolites. EV proteins have been widely investigated as potential biomarkers since they reflect specific patient conditions. However, although many markers have been validated and confirmed using external cohorts of patients and different analytical approaches, no EV protein markers are approved for diagnostic use. This review presents the primary strategies adopted using mass spectrometry and immune-based techniques to identify and validate EV protein biomarkers. We report and discuss recent scientific research focusing on cancer biomarker discovery through EVs, emphasizing their significant potential for the tempestive diagnosis of several cancer typologies. Finally, recent advancements in the standardization of EV isolation and quantitation through the development of easy-to-use and high-throughput kits for sample preparation-that should make protein EV biomarkers more reliable and accessible-are presented. The data reported here showed that there are still several challenges to be addressed before a protein vesicle marker becomes an essential tool in diagnosing cancer.
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Affiliation(s)
- Veronica De Giorgis
- Department of Translational Medicine, University of Piemonte Orientale, via Solaroli 17, Novara 28100, Italy; CAAD, Centre for Translational Research on Autoimmune and Allergic Diseases, Corso Trieste 15/A, Novara 28100, Italy
| | - Elettra Barberis
- CAAD, Centre for Translational Research on Autoimmune and Allergic Diseases, Corso Trieste 15/A, Novara 28100, Italy; Department of Sciences and Technological Innovation, University of Piemonte Orientale, viale T. Michel 11, Alessandria 15121, Italy
| | - Marcello Manfredi
- Department of Translational Medicine, University of Piemonte Orientale, via Solaroli 17, Novara 28100, Italy; CAAD, Centre for Translational Research on Autoimmune and Allergic Diseases, Corso Trieste 15/A, Novara 28100, Italy.
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27
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Rasouli A, Roshangar L, Hosseini M, Pourmohammadfazel A, Nikzad S. Beyond boundaries: The therapeutic potential of exosomes in neural microenvironments in neurological disorders. Neuroscience 2024; 553:98-109. [PMID: 38964450 DOI: 10.1016/j.neuroscience.2024.06.031] [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: 12/30/2023] [Revised: 06/18/2024] [Accepted: 06/25/2024] [Indexed: 07/06/2024]
Abstract
Neurological disorders are a diverse group of conditions that can significantly impact individuals' quality of life. The maintenance of neural microenvironment homeostasis is essential for optimal physiological cellular processes. Perturbations in this delicate balance underlie various pathological manifestations observed across various neurological disorders. Current treatments for neurological disorders face substantial challenges, primarily due to the formidable blood-brain barrier and the intricate nature of neural tissue structures. These obstacles have resulted in a paucity of effective therapies and inefficiencies in patient care. Exosomes, nanoscale vesicles that contain a complex repertoire of biomolecules, are identifiable in various bodily fluids. They hold substantial promise in numerous therapeutic interventions due to their unique attributes, including targeted drug delivery mechanisms and the ability to cross the BBB, thereby enhancing their therapeutic potential. In this review, we investigate the therapeutic potential of exosomes across a range of neurological disorders, including neurodegenerative disorders, traumatic brain injury, peripheral nerve injury, brain tumors, and stroke. Through both in vitro and in vivo studies, our findings underscore the beneficial influence of exosomes in enhancing the neural microenvironment following neurological diseases, offering promise for improved neural recovery and management in these conditions.
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Affiliation(s)
- Arefe Rasouli
- Department of Anatomical Sciences, School of Medicine Tabriz University of Medical Sciences, Tabriz, Iran
| | - Leila Roshangar
- Department of Anatomical Sciences, School of Medicine Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Mohammadbagher Hosseini
- Department of Pediatrics, School of Medicine Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amir Pourmohammadfazel
- Department of Anatomical Sciences, School of Medicine Tabriz University of Medical Sciences, Tabriz, Iran
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28
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Wang Z, Zhou X, Kong Q, He H, Sun J, Qiu W, Zhang L, Yang M. Extracellular Vesicle Preparation and Analysis: A State-of-the-Art Review. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2401069. [PMID: 38874129 PMCID: PMC11321646 DOI: 10.1002/advs.202401069] [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] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 04/11/2024] [Indexed: 06/15/2024]
Abstract
In recent decades, research on Extracellular Vesicles (EVs) has gained prominence in the life sciences due to their critical roles in both health and disease states, offering promising applications in disease diagnosis, drug delivery, and therapy. However, their inherent heterogeneity and complex origins pose significant challenges to their preparation, analysis, and subsequent clinical application. This review is structured to provide an overview of the biogenesis, composition, and various sources of EVs, thereby laying the groundwork for a detailed discussion of contemporary techniques for their preparation and analysis. Particular focus is given to state-of-the-art technologies that employ both microfluidic and non-microfluidic platforms for EV processing. Furthermore, this discourse extends into innovative approaches that incorporate artificial intelligence and cutting-edge electrochemical sensors, with a particular emphasis on single EV analysis. This review proposes current challenges and outlines prospective avenues for future research. The objective is to motivate researchers to innovate and expand methods for the preparation and analysis of EVs, fully unlocking their biomedical potential.
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Affiliation(s)
- Zesheng Wang
- Department of Precision Diagnostic and Therapeutic TechnologyCity University of Hong Kong Shenzhen Futian Research InstituteShenzhenGuangdong518000P. R. China
- Department of Biomedical Sciencesand Tung Biomedical Sciences CentreCity University of Hong KongHong Kong999077P. R. China
- Key Laboratory of Biochip TechnologyBiotech and Health CentreShenzhen Research Institute of City University of Hong KongShenzhen518057P. R. China
| | - Xiaoyu Zhou
- Department of Precision Diagnostic and Therapeutic TechnologyCity University of Hong Kong Shenzhen Futian Research InstituteShenzhenGuangdong518000P. R. China
- Department of Biomedical Sciencesand Tung Biomedical Sciences CentreCity University of Hong KongHong Kong999077P. R. China
- Key Laboratory of Biochip TechnologyBiotech and Health CentreShenzhen Research Institute of City University of Hong KongShenzhen518057P. R. China
| | - Qinglong Kong
- The Second Department of Thoracic SurgeryDalian Municipal Central HospitalDalian116033P. R. China
| | - Huimin He
- Department of Precision Diagnostic and Therapeutic TechnologyCity University of Hong Kong Shenzhen Futian Research InstituteShenzhenGuangdong518000P. R. China
- Department of Biomedical Sciencesand Tung Biomedical Sciences CentreCity University of Hong KongHong Kong999077P. R. China
- Key Laboratory of Biochip TechnologyBiotech and Health CentreShenzhen Research Institute of City University of Hong KongShenzhen518057P. R. China
| | - Jiayu Sun
- Department of Precision Diagnostic and Therapeutic TechnologyCity University of Hong Kong Shenzhen Futian Research InstituteShenzhenGuangdong518000P. R. China
- Department of Biomedical Sciencesand Tung Biomedical Sciences CentreCity University of Hong KongHong Kong999077P. R. China
| | - Wenting Qiu
- Department of Precision Diagnostic and Therapeutic TechnologyCity University of Hong Kong Shenzhen Futian Research InstituteShenzhenGuangdong518000P. R. China
- Department of Biomedical Sciencesand Tung Biomedical Sciences CentreCity University of Hong KongHong Kong999077P. R. China
| | - Liang Zhang
- Department of Precision Diagnostic and Therapeutic TechnologyCity University of Hong Kong Shenzhen Futian Research InstituteShenzhenGuangdong518000P. R. China
- Department of Biomedical Sciencesand Tung Biomedical Sciences CentreCity University of Hong KongHong Kong999077P. R. China
- Key Laboratory of Biochip TechnologyBiotech and Health CentreShenzhen Research Institute of City University of Hong KongShenzhen518057P. R. China
| | - Mengsu Yang
- Department of Precision Diagnostic and Therapeutic TechnologyCity University of Hong Kong Shenzhen Futian Research InstituteShenzhenGuangdong518000P. R. China
- Department of Biomedical Sciencesand Tung Biomedical Sciences CentreCity University of Hong KongHong Kong999077P. R. China
- Key Laboratory of Biochip TechnologyBiotech and Health CentreShenzhen Research Institute of City University of Hong KongShenzhen518057P. R. China
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29
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Guo L, Xiao D, Xing H, Yang G, Yang X. Engineered exosomes as a prospective therapy for diabetic foot ulcers. BURNS & TRAUMA 2024; 12:tkae023. [PMID: 39026930 PMCID: PMC11255484 DOI: 10.1093/burnst/tkae023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 03/29/2024] [Indexed: 07/20/2024]
Abstract
Diabetic foot ulcer (DFU), characterized by high recurrence rate, amputations and mortality, poses a significant challenge in diabetes management. The complex pathology involves dysregulated glucose homeostasis leading to systemic and local microenvironmental complications, including peripheral neuropathy, micro- and macro-angiopathy, recurrent infection, persistent inflammation and dysregulated re-epithelialization. Novel approaches to accelerate DFU healing are actively pursued, with a focus on utilizing exosomes. Exosomes are natural nanovesicles mediating cellular communication and containing diverse functional molecular cargos, including DNA, mRNA, microRNA (miRNA), lncRNA, proteins, lipids and metabolites. While some exosomes show promise in modulating cellular function and promoting ulcer healing, their efficacy is limited by low yield, impurities, low loading content and inadequate targeting. Engineering exosomes to enhance their curative activity represents a potentially more efficient approach for DFUs. This could facilitate focused repair and regeneration of nerves, blood vessels and soft tissue after ulcer development. This review provides an overview of DFU pathogenesis, strategies for exosome engineering and the targeted therapeutic application of engineered exosomes in addressing critical pathological changes associated with DFUs.
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Affiliation(s)
- Lifei Guo
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Chang-Le Xi Street #127, Xi'an 710032, China
- The State Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Chang-Le Xi Street #127, Xi'an 710032, China
- Cadet Team 6 of School of Basic Medicine, Fourth Military Medical University, Chang-Le Xi Street #127, Xi'an 710032, China
| | - Dan Xiao
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Chang-Le Xi Street #127, Xi'an 710032, China
- The State Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Chang-Le Xi Street #127, Xi'an 710032, China
| | - Helin Xing
- Department of Prosthodontics, Beijing Stomatological Hospital and School of Stomatology, Capital Medical University, Tiantanxili Street #4, Dongcheng District, Beijing 100050, China
| | - Guodong Yang
- The State Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Chang-Le Xi Street #127, Xi'an 710032, China
| | - Xuekang Yang
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Chang-Le Xi Street #127, Xi'an 710032, China
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Hu L, Zheng X, Zhou M, Wang J, Tong L, Dong M, Xu T, Li Z. Optimized AF4 combined with density cushion ultracentrifugation enables profiling of high-purity human blood extracellular vesicles. J Extracell Vesicles 2024; 13:e12470. [PMID: 39001700 PMCID: PMC11245685 DOI: 10.1002/jev2.12470] [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: 11/27/2023] [Accepted: 06/11/2024] [Indexed: 07/15/2024] Open
Abstract
Extracellular vesicles (EVs) have emerged as a promising tool for clinical liquid biopsy. However, the identification of EVs derived from blood samples is hindered by the presence of abundant plasma proteins, which impairs the downstream biochemical analysis of EV-associated proteins and nucleic acids. Here, we employed optimized asymmetric flow field-flow fractionation (AF4) combined with density cushion ultracentrifugation (UC) to obtain high-purity and intact EVs with very low lipoprotein contamination from human plasma and serum. Further proteomic analysis revealed more than 1000 EV-associated proteins, a large proportion of which has not been previously reported. Specifically, we found that cell-line-derived EV markers are incompatible with the identification of plasma-EVs and proposed that the proteins MYCT1, TSPAN14, MPIG6B and MYADM, as well as the traditional EV markers CD63 and CD147, are plasma-EV markers. Benefiting from the high-purity of EVs, we conducted comprehensive miRNA profiling of plasma EVs and nanosized particles (NPs), as well as compared plasma- and serum-derived EVs, which provides a valuable resource for the EV research community. Overall, our findings provide a comprehensive assessment of human blood EVs as a basis for clinical biopsy applications.
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Affiliation(s)
- Liqiao Hu
- Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and TechnologyHuazhong University of Science and TechnologyWuhanChina
- Guangzhou National LaboratoryGuangzhouChina
| | - Xinyue Zheng
- Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and TechnologyHuazhong University of Science and TechnologyWuhanChina
| | - Maoge Zhou
- Guangzhou National LaboratoryGuangzhouChina
| | - Jifeng Wang
- Laboratory of Proteomics, Institute of BiophysicsChinese Academy of SciencesBeijingChina
| | - Lingjun Tong
- Jinan Central Hospital, Medical Science and Technology Innovation CenterShandong First Medical University & Shandong Academy of Medical SciencesJinanChina
| | - Ming Dong
- Guangzhou National LaboratoryGuangzhouChina
| | - Tao Xu
- Guangzhou National LaboratoryGuangzhouChina
- Jinan Central Hospital, Medical Science and Technology Innovation CenterShandong First Medical University & Shandong Academy of Medical SciencesJinanChina
- National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesBeijingChina
- School of Biomedical EngineeringGuangzhou Medical UniversityGuangzhouChina
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31
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Aghajanloo B, Hadady H, Ejeian F, Inglis DW, Hughes MP, Tehrani AF, Nasr-Esfahani MH. Biomechanics of circulating cellular and subcellular bioparticles: beyond separation. Cell Commun Signal 2024; 22:331. [PMID: 38886776 PMCID: PMC11181607 DOI: 10.1186/s12964-024-01707-6] [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: 03/21/2024] [Accepted: 06/07/2024] [Indexed: 06/20/2024] Open
Abstract
Biomechanical attributes have emerged as novel markers, providing a reliable means to characterize cellular and subcellular fractions. Numerous studies have identified correlations between these factors and patients' medical status. However, the absence of a thorough overview impedes their applicability in contemporary state-of-the-art therapeutic strategies. In this context, we provide a comprehensive analysis of the dimensions, configuration, rigidity, density, and electrical characteristics of normal and abnormal circulating cells. Subsequently, the discussion broadens to encompass subcellular bioparticles, such as extracellular vesicles (EVs) enriched either from blood cells or other tissues. Notably, cell sizes vary significantly, from 2 μm for platelets to 25 μm for circulating tumor cells (CTCs), enabling the development of size-based separation techniques, such as microfiltration, for specific diagnostic and therapeutic applications. Although cellular density is relatively constant among different circulating bioparticles, it allows for reliable density gradient centrifugation to isolate cells without altering their native state. Additionally, variations in EV surface charges (-6.3 to -45 mV) offer opportunities for electrophoretic and electrostatic separation methods. The distinctive mechanical properties of abnormal cells, compared to their normal counterparts, present an exceptional opportunity for diverse medical and biotechnological approaches. This review also aims to provide a holistic view of the current understanding of popular techniques in this domain that transcend conventional boundaries, focusing on early harvesting of malignant cells from body fluids, designing effective therapeutic options, cell targeting, and resonating with tissue and genetic engineering principles.
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Affiliation(s)
- Behrouz Aghajanloo
- Department of Mechanical Engineering, Isfahan University of Technology, Isfahan, Iran
- Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
- Department of Science, Research and Technology (DISAT), Politecnico di Torino, Turin, Italy
- School of Engineering, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, 2109, Australia
| | - Hanieh Hadady
- Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - Fatemeh Ejeian
- Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
| | - David W Inglis
- School of Engineering, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, 2109, Australia
| | - Michael Pycraft Hughes
- Department of Biomedical Engineering, Khalifa University, Abu Dhabi, United Arab Emirates
| | | | - Mohammad Hossein Nasr-Esfahani
- Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
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32
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Padinharayil H, George A. Small extracellular vesicles: Multi-functional aspects in non-small cell lung carcinoma. Crit Rev Oncol Hematol 2024; 198:104341. [PMID: 38575042 DOI: 10.1016/j.critrevonc.2024.104341] [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: 07/05/2023] [Revised: 03/13/2024] [Accepted: 03/28/2024] [Indexed: 04/06/2024] Open
Abstract
Extracellular vesicles (EVs) impact normal and pathological cellular signaling through bidirectional trafficking. Exosomes, a subset of EVs possess biomolecules including proteins, lipids, DNA fragments and various RNA species reflecting a speculum of their parent cells. The involvement of exosomes in bidirectional communication and their biological constituents substantiate its role in regulating both physiology and pathology, including multiple cancers. Non-small cell lung cancer (NSCLC) is the most common lung cancers (85%) with high incidence, mortality and reduced overall survival. Lack of efficient early diagnostic and therapeutic tools hurdles the management of NSCLC. Interestingly, the exosomes from body fluids similarity with parent cells or tissue offers a potential future multicomponent tool for the early diagnosis of NSCLC. The structural twinning of exosomes with a cell/tissue and the competitive tumor derived exosomes in tumor microenvironment (TME) promotes the unpinning horizons of exosomes as a drug delivery, vaccine, and therapeutic agent. Exosomes in clinical point of view assist to trace: acquired resistance caused by various therapeutic agents, early diagnosis, progression, and surveillance. In an integrated approach, EV biomarkers offer potential cutting-edge techniques for the detection and diagnosis of cancer, though the purification, characterization, and biomarker identification processes for the translational research regarding EVs need further optimization.
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Affiliation(s)
- Hafiza Padinharayil
- Jubilee Centre for Medical Research, Jubilee Mission Medical College and Research Institute, Thrissur-05, Kerala, India
| | - Alex George
- Jubilee Centre for Medical Research, Jubilee Mission Medical College and Research Institute, Thrissur-05, Kerala, India.
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Moghassemi S, Dadashzadeh A, Sousa MJ, Vlieghe H, Yang J, León-Félix CM, Amorim CA. Extracellular vesicles in nanomedicine and regenerative medicine: A review over the last decade. Bioact Mater 2024; 36:126-156. [PMID: 38450204 PMCID: PMC10915394 DOI: 10.1016/j.bioactmat.2024.02.021] [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: 12/01/2023] [Revised: 02/15/2024] [Accepted: 02/19/2024] [Indexed: 03/08/2024] Open
Abstract
Small extracellular vesicles (sEVs) are known to be secreted by a vast majority of cells. These sEVs, specifically exosomes, induce specific cell-to-cell interactions and can activate signaling pathways in recipient cells through fusion or interaction. These nanovesicles possess several desirable properties, making them ideal for regenerative medicine and nanomedicine applications. These properties include exceptional stability, biocompatibility, wide biodistribution, and minimal immunogenicity. However, the practical utilization of sEVs, particularly in clinical settings and at a large scale, is hindered by the expensive procedures required for their isolation, limited circulation lifetime, and suboptimal targeting capacity. Despite these challenges, sEVs have demonstrated a remarkable ability to accommodate various cargoes and have found extensive applications in the biomedical sciences. To overcome the limitations of sEVs and broaden their potential applications, researchers should strive to deepen their understanding of current isolation, loading, and characterization techniques. Additionally, acquiring fundamental knowledge about sEVs origins and employing state-of-the-art methodologies in nanomedicine and regenerative medicine can expand the sEVs research scope. This review provides a comprehensive overview of state-of-the-art exosome-based strategies in diverse nanomedicine domains, encompassing cancer therapy, immunotherapy, and biomarker applications. Furthermore, we emphasize the immense potential of exosomes in regenerative medicine.
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Affiliation(s)
- Saeid Moghassemi
- Pôle de Recherche en Physiopathologie de La Reproduction, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
| | - Arezoo Dadashzadeh
- Pôle de Recherche en Physiopathologie de La Reproduction, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
| | - Maria João Sousa
- Pôle de Recherche en Physiopathologie de La Reproduction, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
| | - Hanne Vlieghe
- Pôle de Recherche en Physiopathologie de La Reproduction, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
| | - Jie Yang
- Pôle de Recherche en Physiopathologie de La Reproduction, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
| | - Cecibel María León-Félix
- Pôle de Recherche en Physiopathologie de La Reproduction, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
| | - Christiani A. Amorim
- Pôle de Recherche en Physiopathologie de La Reproduction, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
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Lu H, Mu Q, Ku W, Zheng Y, Yi P, Lin L, Li P, Wang B, Wu J, Yu D, Zhao W. Functional extracellular vesicles from SHEDs combined with gelatin methacryloyl promote the odontogenic differentiation of DPSCs for pulp regeneration. J Nanobiotechnology 2024; 22:265. [PMID: 38760763 PMCID: PMC11102175 DOI: 10.1186/s12951-024-02542-0] [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: 11/20/2023] [Accepted: 05/09/2024] [Indexed: 05/19/2024] Open
Abstract
BACKGROUND Pulp regeneration is a novel approach for the treatment of immature permanent teeth with pulp necrosis. This technique includes the combination of stem cells, scaffolds, and growth factors. Recently, stem cell-derived extracellular vesicles (EVs) have emerged as a new methodology for pulp regeneration. Emerging evidence has proven that preconditioning is an effective scheme to modify EVs for better therapeutic potency. Meanwhile, proper scaffolding is of great significance to protect EVs from rapid clearance and destruction. This investigation aims to fabricate an injectable hydrogel loaded with EVs from pre-differentiated stem cells from human exfoliated deciduous teeth (SHEDs) and examine their effects on pulp regeneration. RESULTS We successfully employed the odontogenic induction medium (OM) of SHEDs to generate functional EV (OM-EV). The OM-EV at a concentration of 20 µg/mL was demonstrated to promote the proliferation and migration of dental pulp stem cells (DPSCs). The results revealed that OM-EV has a better potential to promote odontogenic differentiation of DPSCs than common EVs (CM-EV) in vitro through Alizarin red phalloidin, alkaline phosphatase staining, and assessment of the expression of odontogenic-related markers. High-throughput sequencing suggests that the superior effects of OM-EV may be attributed to activation of the AMPK/mTOR pathway. Simultaneously, we prepared a photocrosslinkable gelatin methacryloyl (GelMA) to construct an OM-EV-encapsulated hydrogel. The hydrogel exhibited sustained release of OM-EV and good biocompatibility for DPSCs. The released OM-EV from the hydrogel could be internalized by DPSCs, thereby enhancing their survival and migration. In tooth root slices that were subcutaneously transplanted in nude mice, the OM-EV-encapsulated hydrogel was found to facilitate dentinogenesis. After 8 weeks, there was more formation of mineralized tissue, as well as higher levels of dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1). CONCLUSIONS The effects of EV can be substantially enhanced by preconditioning of SHEDs. The functional EVs from SHEDs combined with GelMA are capable of effectively promoting dentinogenesis through upregulating the odontogenic differentiation of DPSCs, which provides a promising therapeutic approach for pulp regeneration.
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Affiliation(s)
- Hui Lu
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China
| | - Qing Mu
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China
| | - Weili Ku
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China
| | - Yexin Zheng
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China
| | - Ping Yi
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China
| | - Ling Lin
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China
| | - Pei Li
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China
| | - Boqun Wang
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China
| | - Jie Wu
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China
| | - Dongsheng Yu
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China.
| | - Wei Zhao
- Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China.
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Javadi M, Gholami Farashah MS, Roshangar L, Soleimani JR. Plasma-derived extracellular vesicles improve mice embryo development. Mol Biol Rep 2024; 51:621. [PMID: 38709430 DOI: 10.1007/s11033-024-09500-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: 08/17/2023] [Accepted: 03/28/2024] [Indexed: 05/07/2024]
Abstract
BACKGROUND To investigate the effect of plasma-derived extracellular vesicles (EVs) or conventional medium in fertilization and early embryo development rate in mice. METHODS AND RESULTS MII oocytes (matured in vivo or in vitro conditions) were obtained from female mice. The extracellular vesicles were isolated by ultracentrifugation of plasma and were analyzed and measured for size and morphology by dynamic light scattering (DLS) and transmission electron microscopy (TEM). By western blotting analysis, the EVs proteins markers such as CD82 protein and heat shock protein 90 (HSP90) were investigated. Incorporating DiI-labeled EVs within the oocyte cytoplasm was visible at 23 h in oocyte cytoplasm. Also, the effective proteins in the early reproductive process were determined in isolated EVs by western blotting. These EVs had a positive effect on the fertilization rate (P < 0.05). The early embryo development (8 cell, morula and blastocyst stages) was higher in groups supplemented with EVs (P < 0.01). CONCLUSION Our findings showed that supplementing in vitro maturation media with EVs derived- plasma was beneficial for mice's embryo development.
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Affiliation(s)
- Maryam Javadi
- Department of Anatomical Sciences, Faculty of Medicine, Zanjan University of Medical Sciences (ZUMS), Zanjan, Iran.
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Mohammad Sadegh Gholami Farashah
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Biology and Anatomical Sciences, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Leila Roshangar
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Jafar Rad Soleimani
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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Mao Z, Wu Y, Kong L, Zhou L, Zhang X, Geng A, Cai J, Yang H, Peili H. Changes in cargoes of platelet derived extracellular vesicles heterogeneous subpopulations induced by PM 0.1--Undisclosed cardiovascular injury communication mechanism. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2024; 348:123845. [PMID: 38522605 DOI: 10.1016/j.envpol.2024.123845] [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: 11/01/2023] [Revised: 02/28/2024] [Accepted: 03/21/2024] [Indexed: 03/26/2024]
Abstract
Epidemiological evidence has indicated a closely link between PM0.1 exposure and the incidence rate of cardiovascular diseases. This study explores the underlying communication roles of platelet-derived extracellular vesicles (PEVs) heterogeneous subpopulations in cardiovascular injury. PEVs and PMEVs which were extracted from platelet-rich plasma (PRP) un-exposure or exposure to PM0.1 by TIM4 affinity beads. By optimizing separation conditions, replacing pipelines, and resetting injection procedures, Asymmetric flow field-flow fractionation (AF4) was employed to separate, purify, characterize, and enrich PEVs and PMEVs heterogeneous subpopulations (small PEVs, PEVs-S/PMEVs-S: <100 nm; medium PEVs, PEVs-M/PMEVs-M: 100-200 nm; and large PEVs, PEVs-L/PMEVs-L: >200 nm). The results showed that the cargoes of PMEVs heterogeneous subpopulations which were released by PRP stimulated by PM0.1 were changed obviously. Moreover, compared with PEVs, PMEVs can lead to a decrease in the survival rate of Human Umbilical Vein Endothelial Cells (HUVECs). In PMEVs-S subpopulations, the alterations of lipids associated with membrane fusion and cell signaling transport (such as PC, Cer), as well as miRNAs related to inflammation, angiogenesis, and migration (miR-223, miR-22, miR-126, and miR-150), are similar to those in PMEVs-M subpopulations but distinct from PMEVs-L subpopulations. This study revealed the diverse communication mechanisms underlying PM0.1-induced cardiovascular injury, thereby offering potential avenues for the development of new biomarkers and therapeutic targets.
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Affiliation(s)
- Zhen Mao
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China
| | - Yingting Wu
- School of Pharmacy, Capital Medical University, No. 10 Xitoutiao You An Men, Beijing, 100069, China
| | - Ling Kong
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China; Central Laboratory, Xuanwu Hospital Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Beijing Institute for Brain Disorders, National Clinical Research Center for Geriatric Disorders, Beijing, 100053, China
| | - Lihong Zhou
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China
| | - Xiaodan Zhang
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China
| | - Aobo Geng
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China
| | - Jin Cai
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China
| | - Hong Yang
- Yanjing Medical College, Capital Medical University, No.4 Dadong Road, Shunyi District, Beijing, 101300, China
| | - Huang Peili
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
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Bai C, Liu J, Zhang X, Li Y, Qin Q, Song H, Yuan C, Huang Z. Research status and challenges of plant-derived exosome-like nanoparticles. Biomed Pharmacother 2024; 174:116543. [PMID: 38608523 DOI: 10.1016/j.biopha.2024.116543] [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: 01/08/2024] [Revised: 03/26/2024] [Accepted: 04/04/2024] [Indexed: 04/14/2024] Open
Abstract
In recent years, there has been an increasing number of related studies on exosomes. Most studies have focused on exosomes derived from mammals, confirming the important role that exosomes play in cell communication. Plants, as a natural ingredient, plant-derived exosomes have been confirmed to have similar structures and functions to mammalian-derived exosomes. Plant-derived exosome-like nanoparticles (PELNs) are lipid bilayer membrane nanovesicles containing bioactive constituents such as miRNA, mRNA, protein, and lipids obtained from plant cells, that can participate in intercellular communication and mediate transboundary communication, have high bioavailability and low immunogenicity, are relatively safe, and have been shown to play an important role in maintaining cell homeostasis and preventing, and treating a variety of diseases. In this review, we describe the biogenesis, isolation and purification methods, structural composition, stability, safety, function of PELNs and challenges. The functions of PELNs in anti-inflammatory, antioxidant, antitumor and drug delivery are mainly described, and the status of research on exosome nanoparticles of Chinese herbal medicines is outlined. Overall, we summarized the importance of PELNs and the latest research results in this field and provided a theoretical basis for the future research and clinical application of PELNs.
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Affiliation(s)
- Chunmei Bai
- The Fifth Clinical Medical College of Shanxi Medical University, Xinjian South Road, Yingze District, Taiyuan City, Shanxi Province, 030001, China
| | - Jianrong Liu
- The Fifth Clinical Medical College of Shanxi Medical University, Xinjian South Road, Yingze District, Taiyuan City, Shanxi Province, 030001, China; Department of reproductive medicine of Shanxi Provincial People's Hospital, Shuangtaxi Street, Taiyuan City, 030012, China.
| | - Xumin Zhang
- The Fifth Clinical Medical College of Shanxi Medical University, Xinjian South Road, Yingze District, Taiyuan City, Shanxi Province, 030001, China
| | - Yang Li
- The Fifth Clinical Medical College of Shanxi Medical University, Xinjian South Road, Yingze District, Taiyuan City, Shanxi Province, 030001, China
| | - Qin Qin
- The Fifth Clinical Medical College of Shanxi Medical University, Xinjian South Road, Yingze District, Taiyuan City, Shanxi Province, 030001, China; Department of reproductive medicine of Shanxi Provincial People's Hospital, Shuangtaxi Street, Taiyuan City, 030012, China
| | - Haixia Song
- Department of reproductive medicine of Shanxi Provincial People's Hospital, Shuangtaxi Street, Taiyuan City, 030012, China
| | - Caixia Yuan
- Department of reproductive medicine of Shanxi Provincial People's Hospital, Shuangtaxi Street, Taiyuan City, 030012, China
| | - Ziwei Huang
- Department of reproductive medicine of Shanxi Provincial People's Hospital, Shuangtaxi Street, Taiyuan City, 030012, China
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Qiu H, Liang J, Yang G, Xie Z, Wang Z, Wang L, Zhang J, Nanda HS, Zhou H, Huang Y, Peng X, Lu C, Chen H, Zhou Y. Application of exosomes in tumor immunity: recent progresses. Front Cell Dev Biol 2024; 12:1372847. [PMID: 38633106 PMCID: PMC11021734 DOI: 10.3389/fcell.2024.1372847] [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: 01/18/2024] [Accepted: 03/13/2024] [Indexed: 04/19/2024] Open
Abstract
Exosomes are small extracellular vesicles secreted by cells, ranging in size from 30 to 150 nm. They contain proteins, nucleic acids, lipids, and other bioactive molecules, which play a crucial role in intercellular communication and material transfer. In tumor immunity, exosomes present various functions while the following two are of great importance: regulating the immune response and serving as delivery carriers. This review starts with the introduction of the formation, compositions, functions, isolation, characterization, and applications of exosomes, and subsequently discusses the current status of exosomes in tumor immunotherapy, and the recent applications of exosome-based tumor immunity regulation and antitumor drug delivery. Finally, current challenge and future prospects are proposed and hope to demonstrate inspiration for targeted readers in the field.
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Affiliation(s)
- Haiyan Qiu
- School of Pharmacy, Guangdong Medical University, Dongguan, China
| | - Junting Liang
- School of Pharmacy, Guangdong Medical University, Dongguan, China
| | - Guang Yang
- School of Pharmacy, Guangdong Medical University, Dongguan, China
| | - Zhenyu Xie
- School of Pharmacy, Guangdong Medical University, Dongguan, China
| | - Zhenpeng Wang
- School of Pharmacy, Guangdong Medical University, Dongguan, China
| | - Liyan Wang
- School of Pharmacy, Guangdong Medical University, Dongguan, China
| | - Jingying Zhang
- The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China
| | - Himansu Sekhar Nanda
- Biomedical Engineering and Technology Lab, Discipline of Mechanical Engineering, PDPM Indian Institute of Information Technology Design and Manufacturing Jabalpur, Jabalpur, Madhya Pradesh, India
| | - Hui Zhou
- School of Pharmacy, Guangdong Medical University, Dongguan, China
| | - Yong Huang
- School of Pharmacy, Guangdong Medical University, Dongguan, China
| | - Xinsheng Peng
- School of Pharmacy, Guangdong Medical University, Dongguan, China
| | - Chengyu Lu
- School of Pharmacy, Guangdong Medical University, Dongguan, China
| | - Huizhi Chen
- School of Pharmacy, Guangdong Medical University, Dongguan, China
- The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China
| | - Yubin Zhou
- School of Pharmacy, Guangdong Medical University, Dongguan, China
- The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China
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Sun T, Li M, Liu Q, Yu A, Cheng K, Ma J, Murphy S, McNutt PM, Zhang Y. Insights into optimizing exosome therapies for acute skin wound healing and other tissue repair. Front Med 2024; 18:258-284. [PMID: 38216854 PMCID: PMC11283324 DOI: 10.1007/s11684-023-1031-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Accepted: 09/15/2023] [Indexed: 01/14/2024]
Abstract
Exosome therapy holds great promise as a novel approach to improve acute skin wound healing. This review provides a comprehensive overview of the current understanding of exosome biology and its potential applications in acute skin wound healing and beyond. Exosomes, small extracellular vesicles secreted by various stem cells, have emerged as potent mediators of intercellular communication and tissue repair. One advantage of exosome therapy is its ability to avoid potential risks associated with stem cell therapy, such as immune rejection or stem cells differentiating into unwanted cell types. However, further research is necessary to optimize exosome therapy, not only in the areas of exosome isolation, characterization, and engineering, but also in determining the optimal dose, timing, administration, and frequency of exosome therapy. Thus, optimization of exosome therapy is critical for the development of more effective and safer exosome-based therapies for acute skin wound healing and other diseases induced by cancer, ischemia, or inflammation. This review provides valuable insights into the potential of exosome therapy and highlights the need for further research to optimize exosome therapy for clinical use.
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Affiliation(s)
- Tianjing Sun
- Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, China
| | - Mo Li
- Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, China
| | - Qi Liu
- Department of Nephrology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, China.
| | - Anyong Yu
- Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, China.
| | - Kun Cheng
- Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, 64108, USA
| | - Jianxing Ma
- Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA
| | - Sean Murphy
- Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27109, USA
| | - Patrick Michael McNutt
- Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27109, USA
| | - Yuanyuan Zhang
- Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27109, USA.
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Gupta R, Gupta J, Roy S. Exosomes: Key Players for Treatment of Cancer and Their Future Perspectives. Assay Drug Dev Technol 2024; 22:118-147. [PMID: 38407852 DOI: 10.1089/adt.2023.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/27/2024] Open
Affiliation(s)
- Reena Gupta
- Institute of Pharmaceutical Research, GLA University, Mathura, India
| | - Jitendra Gupta
- Institute of Pharmaceutical Research, GLA University, Mathura, India
| | - Suchismita Roy
- Institute of Pharmaceutical Research, GLA University, Mathura, India
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Soong WJ, Wang CH, Chen C, Lee GB. Nanoscale sorting of extracellular vesicles via optically-induced dielectrophoresis on an integrated microfluidic system. LAB ON A CHIP 2024; 24:1965-1976. [PMID: 38357980 DOI: 10.1039/d3lc01007d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/16/2024]
Abstract
We reported a microfluidic system for sorting of extracellular vesicles (EVs), which can house DNAs, RNAs, lipids, proteins, and metabolites that are important in intercellular communication. Their presence within bodily fluids has demonstrated potential in both clinical diagnostic and therapeutic applications. Furthermore, EVs exhibit distinct subtypes categorized by their sizes, each endowed with unique biophysical properties. Despite several existing techniques for EV isolation and purification, diminished purity and prolonged processing times still hamper clinical utility; comprehensive capture of EVs remains an ongoing pursuit. To address these challenges, we devised an innovative method for automated sorting of nano-scale EVs employing optically-induced dielectrophoresis on an integrated microfluidic chip. With this approach, EVs of three distinct size categories (small: 100-150 nm, medium-sized: 150-225 nm, and large: 225-350 nm) could be isolated at a purity of 86%. This new method has substantial potential in expediting EV research and diagnostics.
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Affiliation(s)
- Wei-Jen Soong
- Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
| | - Chih-Hung Wang
- Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
| | - Chihchen Chen
- Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
- Institute of NanoEngineering and MicroSystems, National Tsing Hua University, Hsinchu, Taiwan
| | - Gwo-Bin Lee
- Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
- Institute of NanoEngineering and MicroSystems, National Tsing Hua University, Hsinchu, Taiwan
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Yang LY, Li CQ, Zhang YL, Ma MW, Cheng W, Zhang GJ. Emerging Drug Delivery Vectors: Engineering of Plant-Derived Nanovesicles and Their Applications in Biomedicine. Int J Nanomedicine 2024; 19:2591-2610. [PMID: 38505167 PMCID: PMC10949304 DOI: 10.2147/ijn.s454794] [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: 12/13/2023] [Accepted: 02/28/2024] [Indexed: 03/21/2024] Open
Abstract
Extracellular vesicles can transmit intercellular information and transport biomolecules to recipient cells during various pathophysiological processes in the organism. Animal cell exosomes have been identified as potential nanodrugs delivery vehicles, yet they have some shortcomings such as high immunogenicity, high cytotoxicity, and complicated preparation procedures. In addition to exosomes, plant-derived extracellular vesicles (PDVs), which carry a variety of active substances, are another promising nano-transport vehicles emerging in recent years due to their stable physicochemical properties, wide source, and low cost. This work briefly introduces the collection and characterization of PDVs, then focuses on the application of PDVs as natural or engineered drug carriers in biomedicine, and finally discusses the development and challenges of PDVs in future applications.
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Affiliation(s)
- Lu-Yao Yang
- School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, People’s Republic of China
| | - Chao-Qing Li
- School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, People’s Republic of China
- Hubei Shizhen Laboratory, Wuhan, 430065, People’s Republic of China
| | - Yu-Lin Zhang
- School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, People’s Republic of China
- Hubei Shizhen Laboratory, Wuhan, 430065, People’s Republic of China
| | - Meng-Wen Ma
- Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, People’s Republic of China
| | - Wan Cheng
- Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, People’s Republic of China
| | - Guo-Jun Zhang
- School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, People’s Republic of China
- Hubei Shizhen Laboratory, Wuhan, 430065, People’s Republic of China
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Madhan S, Dhar R, Devi A. Plant-derived exosomes: a green approach for cancer drug delivery. J Mater Chem B 2024; 12:2236-2252. [PMID: 38351750 DOI: 10.1039/d3tb02752j] [Citation(s) in RCA: 18] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/29/2024]
Abstract
Plant-derived exosomes (PDEs) are natural extracellular vesicles (EVs). In the current decade, they have been highlighted for cancer therapeutic development. Cancer is a global health crisis and it requires an effective, affordable, and less side effect-based treatment. Emerging research based on PDEs suggests that they have immense potential to be considered as a therapeutic option. Research evidences indicate that PDEs' internal molecular cargos show impressive cancer prevention activity with less toxicity. PDEs-based drug delivery systems overcome several limitations of traditional drug delivery tools. Extraction of PDEs from plant sources employ diverse methodologies, encompassing ultracentrifugation, immunoaffinity, size-based isolation, and precipitation, each with distinct advantages and limitations. The core constituents of PDEs comprise of lipids, proteins, DNA, and RNA. Worldwide, a few clinical trials on plant-derived exosomes are underway, and regulatory affairs for their use as therapeutic agents are still not understood with clarity. This review aims to comprehensively analyze the current state of research on plant-derived exosomes as a promising avenue for drug delivery, highlighting anticancer activity, challenges, and future orientation in effective cancer therapeutic development.
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Affiliation(s)
- Shrishti Madhan
- Cancer and Stem Cell Biology Laboratory, Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu District - 603 203, Tamil Nadu, India.
| | - Rajib Dhar
- Cancer and Stem Cell Biology Laboratory, Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu District - 603 203, Tamil Nadu, India.
| | - Arikketh Devi
- Cancer and Stem Cell Biology Laboratory, Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu District - 603 203, Tamil Nadu, India.
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Kumar MA, Baba SK, Sadida HQ, Marzooqi SA, Jerobin J, Altemani FH, Algehainy N, Alanazi MA, Abou-Samra AB, Kumar R, Al-Shabeeb Akil AS, Macha MA, Mir R, Bhat AA. Extracellular vesicles as tools and targets in therapy for diseases. Signal Transduct Target Ther 2024; 9:27. [PMID: 38311623 PMCID: PMC10838959 DOI: 10.1038/s41392-024-01735-1] [Citation(s) in RCA: 166] [Impact Index Per Article: 166.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Revised: 12/20/2023] [Accepted: 12/24/2023] [Indexed: 02/06/2024] Open
Abstract
Extracellular vesicles (EVs) are nano-sized, membranous structures secreted into the extracellular space. They exhibit diverse sizes, contents, and surface markers and are ubiquitously released from cells under normal and pathological conditions. Human serum is a rich source of these EVs, though their isolation from serum proteins and non-EV lipid particles poses challenges. These vesicles transport various cellular components such as proteins, mRNAs, miRNAs, DNA, and lipids across distances, influencing numerous physiological and pathological events, including those within the tumor microenvironment (TME). Their pivotal roles in cellular communication make EVs promising candidates for therapeutic agents, drug delivery systems, and disease biomarkers. Especially in cancer diagnostics, EV detection can pave the way for early identification and offers potential as diagnostic biomarkers. Moreover, various EV subtypes are emerging as targeted drug delivery tools, highlighting their potential clinical significance. The need for non-invasive biomarkers to monitor biological processes for diagnostic and therapeutic purposes remains unfulfilled. Tapping into the unique composition of EVs could unlock advanced diagnostic and therapeutic avenues in the future. In this review, we discuss in detail the roles of EVs across various conditions, including cancers (encompassing head and neck, lung, gastric, breast, and hepatocellular carcinoma), neurodegenerative disorders, diabetes, viral infections, autoimmune and renal diseases, emphasizing the potential advancements in molecular diagnostics and drug delivery.
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Affiliation(s)
- Mudasir A Kumar
- Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Awantipora, Kashmir, 192122, India
| | - Sadaf K Baba
- Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Awantipora, Kashmir, 192122, India
| | - Hana Q Sadida
- Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha, Qatar
| | - Sara Al Marzooqi
- Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha, Qatar
| | - Jayakumar Jerobin
- Qatar Metabolic Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
| | - Faisal H Altemani
- Department of Medical Laboratory Technology, Prince Fahad Bin Sultan Chair for Biomedical Research, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia
| | - Naseh Algehainy
- Department of Medical Laboratory Technology, Prince Fahad Bin Sultan Chair for Biomedical Research, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia
| | - Mohammad A Alanazi
- Department of Medical Laboratory Technology, Prince Fahad Bin Sultan Chair for Biomedical Research, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia
| | - Abdul-Badi Abou-Samra
- Qatar Metabolic Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
| | - Rakesh Kumar
- School of Biotechnology, Shri Mata Vaishno Devi University, Katra, India
| | - Ammira S Al-Shabeeb Akil
- Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha, Qatar
| | - Muzafar A Macha
- Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Awantipora, Kashmir, 192122, India
| | - Rashid Mir
- Department of Medical Laboratory Technology, Prince Fahad Bin Sultan Chair for Biomedical Research, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia.
| | - Ajaz A Bhat
- Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, Doha, Qatar.
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Welsh JA, Goberdhan DCI, O'Driscoll L, Buzas EI, Blenkiron C, Bussolati B, Cai H, Di Vizio D, Driedonks TAP, Erdbrügger U, Falcon‐Perez JM, Fu Q, Hill AF, Lenassi M, Lim SK, Mahoney MG, Mohanty S, Möller A, Nieuwland R, Ochiya T, Sahoo S, Torrecilhas AC, Zheng L, Zijlstra A, Abuelreich S, Bagabas R, Bergese P, Bridges EM, Brucale M, Burger D, Carney RP, Cocucci E, Colombo F, Crescitelli R, Hanser E, Harris AL, Haughey NJ, Hendrix A, Ivanov AR, Jovanovic‐Talisman T, Kruh‐Garcia NA, Ku'ulei‐Lyn Faustino V, Kyburz D, Lässer C, Lennon KM, Lötvall J, Maddox AL, Martens‐Uzunova ES, Mizenko RR, Newman LA, Ridolfi A, Rohde E, Rojalin T, Rowland A, Saftics A, Sandau US, Saugstad JA, Shekari F, Swift S, Ter‐Ovanesyan D, Tosar JP, Useckaite Z, Valle F, Varga Z, van der Pol E, van Herwijnen MJC, Wauben MHM, Wehman AM, Williams S, Zendrini A, Zimmerman AJ, MISEV Consortium, Théry C, Witwer KW. Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches. J Extracell Vesicles 2024; 13:e12404. [PMID: 38326288 PMCID: PMC10850029 DOI: 10.1002/jev2.12404] [Citation(s) in RCA: 1148] [Impact Index Per Article: 1148.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 12/15/2023] [Accepted: 12/19/2023] [Indexed: 02/09/2024] Open
Abstract
Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly.
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Affiliation(s)
- Joshua A. Welsh
- Translational Nanobiology Section, Laboratory of PathologyNational Cancer Institute, National Institutes of HealthBethesdaMarylandUSA
| | - Deborah C. I. Goberdhan
- Nuffield Department of Women's and Reproductive HealthUniversity of Oxford, Women's Centre, John Radcliffe HospitalOxfordUK
| | - Lorraine O'Driscoll
- School of Pharmacy and Pharmaceutical SciencesTrinity College DublinDublinIreland
- Trinity Biomedical Sciences InstituteTrinity College DublinDublinIreland
- Trinity St. James's Cancer InstituteTrinity College DublinDublinIreland
| | - Edit I. Buzas
- Department of Genetics, Cell‐ and ImmunobiologySemmelweis UniversityBudapestHungary
- HCEMM‐SU Extracellular Vesicle Research GroupSemmelweis UniversityBudapestHungary
- HUN‐REN‐SU Translational Extracellular Vesicle Research GroupSemmelweis UniversityBudapestHungary
| | - Cherie Blenkiron
- Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand
| | - Benedetta Bussolati
- Department of Molecular Biotechnology and Health SciencesUniversity of TurinTurinItaly
| | | | - Dolores Di Vizio
- Department of Surgery, Division of Cancer Biology and TherapeuticsCedars‐Sinai Medical CenterLos AngelesCaliforniaUSA
| | - Tom A. P. Driedonks
- Department CDL ResearchUniversity Medical Center UtrechtUtrechtThe Netherlands
| | - Uta Erdbrügger
- University of Virginia Health SystemCharlottesvilleVirginiaUSA
| | - Juan M. Falcon‐Perez
- Exosomes Laboratory, Center for Cooperative Research in BiosciencesBasque Research and Technology AllianceDerioSpain
- Metabolomics Platform, Center for Cooperative Research in BiosciencesBasque Research and Technology AllianceDerioSpain
- IKERBASQUE, Basque Foundation for ScienceBilbaoSpain
| | - Qing‐Ling Fu
- Otorhinolaryngology Hospital, The First Affiliated HospitalSun Yat‐sen UniversityGuangzhouChina
- Extracellular Vesicle Research and Clinical Translational CenterThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhouChina
| | - Andrew F. Hill
- Institute for Health and SportVictoria UniversityMelbourneAustralia
| | - Metka Lenassi
- Faculty of MedicineUniversity of LjubljanaLjubljanaSlovenia
| | - Sai Kiang Lim
- Institute of Molecular and Cell Biology (IMCB)Agency for Science, Technology and Research (A*STAR)SingaporeSingapore
- Paracrine Therapeutics Pte. Ltd.SingaporeSingapore
- Department of Surgery, YLL School of MedicineNational University SingaporeSingaporeSingapore
| | - Mỹ G. Mahoney
- Thomas Jefferson UniversityPhiladelphiaPennsylvaniaUSA
| | - Sujata Mohanty
- Stem Cell FacilityAll India Institute of Medical SciencesNew DelhiIndia
| | - Andreas Möller
- Chinese University of Hong KongHong KongHong Kong S.A.R.
- QIMR Berghofer Medical Research InstituteBrisbaneAustralia
| | - Rienk Nieuwland
- Laboratory of Experimental Clinical Chemistry, Amsterdam University Medical Centers, Location AMCUniversity of AmsterdamAmsterdamThe Netherlands
- Amsterdam Vesicle Center, Amsterdam University Medical Centers, Location AMCUniversity of AmsterdamAmsterdamThe Netherlands
| | | | - Susmita Sahoo
- Icahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Ana C. Torrecilhas
- Laboratório de Imunologia Celular e Bioquímica de Fungos e Protozoários, Departamento de Ciências Farmacêuticas, Instituto de Ciências Ambientais, Químicas e FarmacêuticasUniversidade Federal de São Paulo (UNIFESP) Campus DiademaDiademaBrazil
| | - Lei Zheng
- Department of Laboratory Medicine, Nanfang HospitalSouthern Medical UniversityGuangzhouChina
| | - Andries Zijlstra
- Department of PathologyVanderbilt University Medical CenterNashvilleTennesseeUSA
- GenentechSouth San FranciscoCaliforniaUSA
| | - Sarah Abuelreich
- Department of Molecular Medicine, Beckman Research InstituteCity of Hope Comprehensive Cancer CenterDuarteCaliforniaUSA
| | - Reem Bagabas
- Department of Molecular Medicine, Beckman Research InstituteCity of Hope Comprehensive Cancer CenterDuarteCaliforniaUSA
| | - Paolo Bergese
- Department of Molecular and Translational MedicineUniversity of BresciaBresciaItaly
- Center for Colloid and Surface Science (CSGI)FlorenceItaly
- National Center for Gene Therapy and Drugs based on RNA TechnologyPaduaItaly
| | - Esther M. Bridges
- Weatherall Institute of Molecular MedicineUniversity of OxfordOxfordUK
| | - Marco Brucale
- Consiglio Nazionale delle Ricerche ‐ Istituto per lo Studio dei Materiali NanostrutturatiBolognaItaly
- Consorzio Interuniversitario per lo Sviluppo dei Sistemi a Grande InterfaseFlorenceItaly
| | - Dylan Burger
- Kidney Research CentreOttawa Hopsital Research InstituteOttawaCanada
- Department of Cellular and Molecular MedicineUniversity of OttawaOttawaCanada
- School of Pharmaceutical SciencesUniversity of OttawaOttawaCanada
| | - Randy P. Carney
- Department of Biomedical EngineeringUniversity of CaliforniaDavisCaliforniaUSA
| | - Emanuele Cocucci
- Division of Pharmaceutics and Pharmacology, College of PharmacyThe Ohio State UniversityColumbusOhioUSA
- Comprehensive Cancer CenterThe Ohio State UniversityColumbusOhioUSA
| | - Federico Colombo
- Division of Pharmaceutics and Pharmacology, College of PharmacyThe Ohio State UniversityColumbusOhioUSA
| | - Rossella Crescitelli
- Sahlgrenska Center for Cancer Research, Department of Surgery, Institute of Clinical SciencesSahlgrenska Academy, University of GothenburgGothenburgSweden
- Wallenberg Centre for Molecular and Translational Medicine, Institute of Clinical SciencesSahlgrenska Academy, University of GothenburgGothenburgSweden
| | - Edveena Hanser
- Department of BiomedicineUniversity Hospital BaselBaselSwitzerland
- Department of BiomedicineUniversity of BaselBaselSwitzerland
| | | | - Norman J. Haughey
- Departments of Neurology and PsychiatryJohns Hopkins University School of MedicineBaltimoreMarylandUSA
| | - An Hendrix
- Laboratory of Experimental Cancer Research, Department of Human Structure and RepairGhent UniversityGhentBelgium
- Cancer Research Institute GhentGhentBelgium
| | - Alexander R. Ivanov
- Barnett Institute of Chemical and Biological Analysis, Department of Chemistry and Chemical BiologyNortheastern UniversityBostonMassachusettsUSA
| | - Tijana Jovanovic‐Talisman
- Department of Cancer Biology and Molecular Medicine, Beckman Research InstituteCity of Hope Comprehensive Cancer CenterDuarteCaliforniaUSA
| | - Nicole A. Kruh‐Garcia
- Bio‐pharmaceutical Manufacturing and Academic Resource Center (BioMARC)Infectious Disease Research Center, Colorado State UniversityFort CollinsColoradoUSA
| | - Vroniqa Ku'ulei‐Lyn Faustino
- Department of Molecular Medicine, Beckman Research InstituteCity of Hope Comprehensive Cancer CenterDuarteCaliforniaUSA
| | - Diego Kyburz
- Department of BiomedicineUniversity of BaselBaselSwitzerland
- Department of RheumatologyUniversity Hospital BaselBaselSwitzerland
| | - Cecilia Lässer
- Krefting Research Centre, Department of Internal Medicine and Clinical NutritionInstitute of Medicine at Sahlgrenska Academy, University of GothenburgGothenburgSweden
| | - Kathleen M. Lennon
- Department of Molecular Medicine, Beckman Research InstituteCity of Hope Comprehensive Cancer CenterDuarteCaliforniaUSA
| | - Jan Lötvall
- Krefting Research Centre, Institute of Medicine at Sahlgrenska AcademyUniversity of GothenburgGothenburgSweden
| | - Adam L. Maddox
- Department of Molecular Medicine, Beckman Research InstituteCity of Hope Comprehensive Cancer CenterDuarteCaliforniaUSA
| | - Elena S. Martens‐Uzunova
- Erasmus MC Cancer InstituteUniversity Medical Center Rotterdam, Department of UrologyRotterdamThe Netherlands
| | - Rachel R. Mizenko
- Department of Biomedical EngineeringUniversity of CaliforniaDavisCaliforniaUSA
| | - Lauren A. Newman
- College of Medicine and Public HealthFlinders UniversityAdelaideAustralia
| | - Andrea Ridolfi
- Department of Physics and Astronomy, and LaserLaB AmsterdamVrije Universiteit AmsterdamAmsterdamThe Netherlands
| | - Eva Rohde
- Department of Transfusion Medicine, University HospitalSalzburger Landeskliniken GmbH of Paracelsus Medical UniversitySalzburgAustria
- GMP Unit, Paracelsus Medical UniversitySalzburgAustria
- Transfer Centre for Extracellular Vesicle Theralytic Technologies, EV‐TTSalzburgAustria
| | - Tatu Rojalin
- Department of Biomedical EngineeringUniversity of CaliforniaDavisCaliforniaUSA
- Expansion Therapeutics, Structural Biology and BiophysicsJupiterFloridaUSA
| | - Andrew Rowland
- College of Medicine and Public HealthFlinders UniversityAdelaideAustralia
| | - Andras Saftics
- Department of Molecular Medicine, Beckman Research InstituteCity of Hope Comprehensive Cancer CenterDuarteCaliforniaUSA
| | - Ursula S. Sandau
- Department of Anesthesiology & Perioperative MedicineOregon Health & Science UniversityPortlandOregonUSA
| | - Julie A. Saugstad
- Department of Anesthesiology & Perioperative MedicineOregon Health & Science UniversityPortlandOregonUSA
| | - Faezeh Shekari
- Department of Stem Cells and Developmental Biology, Cell Science Research CenterRoyan Institute for Stem Cell Biology and Technology, ACECRTehranIran
- Celer DiagnosticsTorontoCanada
| | - Simon Swift
- Waipapa Taumata Rau University of AucklandAucklandNew Zealand
| | - Dmitry Ter‐Ovanesyan
- Wyss Institute for Biologically Inspired EngineeringHarvard UniversityBostonMassachusettsUSA
| | - Juan P. Tosar
- Universidad de la RepúblicaMontevideoUruguay
- Institut Pasteur de MontevideoMontevideoUruguay
| | - Zivile Useckaite
- College of Medicine and Public HealthFlinders UniversityAdelaideAustralia
| | - Francesco Valle
- Consiglio Nazionale delle Ricerche ‐ Istituto per lo Studio dei Materiali NanostrutturatiBolognaItaly
- Consorzio Interuniversitario per lo Sviluppo dei Sistemi a Grande InterfaseFlorenceItaly
| | - Zoltan Varga
- Biological Nanochemistry Research GroupInstitute of Materials and Environmental Chemistry, Research Centre for Natural SciencesBudapestHungary
- Department of Biophysics and Radiation BiologySemmelweis UniversityBudapestHungary
| | - Edwin van der Pol
- Amsterdam Vesicle Center, Amsterdam University Medical Centers, Location AMCUniversity of AmsterdamAmsterdamThe Netherlands
- Biomedical Engineering and Physics, Amsterdam UMC, location AMCUniversity of AmsterdamAmsterdamThe Netherlands
- Laboratory of Experimental Clinical Chemistry, Amsterdam UMC, location AMCUniversity of AmsterdamAmsterdamThe Netherlands
| | - Martijn J. C. van Herwijnen
- Department of Biomolecular Health Sciences, Faculty of Veterinary MedicineUtrecht UniversityUtrechtThe Netherlands
| | - Marca H. M. Wauben
- Department of Biomolecular Health Sciences, Faculty of Veterinary MedicineUtrecht UniversityUtrechtThe Netherlands
| | | | | | - Andrea Zendrini
- Department of Molecular and Translational MedicineUniversity of BresciaBresciaItaly
- Center for Colloid and Surface Science (CSGI)FlorenceItaly
| | - Alan J. Zimmerman
- Barnett Institute of Chemical and Biological Analysis, Department of Chemistry and Chemical BiologyNortheastern UniversityBostonMassachusettsUSA
| | | | - Clotilde Théry
- Institut Curie, INSERM U932PSL UniversityParisFrance
- CurieCoreTech Extracellular Vesicles, Institut CurieParisFrance
| | - Kenneth W. Witwer
- Department of Molecular and Comparative PathobiologyJohns Hopkins University School of MedicineBaltimoreMarylandUSA
- EV Core Facility “EXCEL”, Institute for Basic Biomedical SciencesJohns Hopkins University School of MedicineBaltimoreMarylandUSA
- The Richman Family Precision Medicine Center of Excellence in Alzheimer's DiseaseJohns Hopkins University School of MedicineBaltimoreMarylandUSA
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Koch LF, Best T, Wüstenhagen E, Adrian K, Rammo O, Saul MJ. Novel insights into the isolation of extracellular vesicles by anion exchange chromatography. Front Bioeng Biotechnol 2024; 11:1298892. [PMID: 38312509 PMCID: PMC10836363 DOI: 10.3389/fbioe.2023.1298892] [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: 09/22/2023] [Accepted: 12/12/2023] [Indexed: 02/06/2024] Open
Abstract
Extracellular vesicles (EVs) are membrane structures enclosed by a lipid bilayer that are released into the extracellular space by all types of cells. EVs are involved in many physiological processes by transporting biologically active substances. Interest in EVs for diagnostic biomarker research and therapeutic drug delivery applications has increased in recent years. The realization of the full therapeutic potential of EVs is currently hampered by the lack of a suitable technology for the isolation and purification of EVs for downstream pharmaceutical applications. Anion Exchange Chromatography (AEX) is an established method in which specific charges on the AEX matrix can exploit charges on the surface of EVs and their interactions to provide a productive and scalable separation and purification method. The established AEX method using Eshmuno® Q, a strong tentacle anion exchange resin, was used to demonstrate the principal feasibility of AEX-based isolation and gain insight into isolated EV properties. Using several EV analysis techniques to provide a more detailed insight into EV populations during AEX isolation, we demonstrated that although the composition of CD9/63/81 remained constant for tetraspanin positive EVs, the size distribution and purity changed during elution. Higher salt concentrations eluted larger tetraspanin negative vesicles.
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Affiliation(s)
- Leon F. Koch
- Department of Biology, Technische Universität Darmstadt, Darmstadt, Germany
| | - Tatjana Best
- Department of Biology, Technische Universität Darmstadt, Darmstadt, Germany
- Merck Life Science KGaA, Darmstadt, Germany
| | | | | | | | - Meike J. Saul
- Department of Biology, Technische Universität Darmstadt, Darmstadt, Germany
- Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Universtiy Cancer Center Hamburg, University Clinic Hamburg-Eppendorf, Hamburg, Germany
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47
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Kim SH, Keum B, Kwak S, Byun J, Shin JM, Kim TH. Therapeutic Applications of Extracellular Vesicles in Inflammatory Bowel Disease. Int J Mol Sci 2024; 25:745. [PMID: 38255819 PMCID: PMC10815267 DOI: 10.3390/ijms25020745] [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: 11/29/2023] [Revised: 12/28/2023] [Accepted: 01/02/2024] [Indexed: 01/24/2024] Open
Abstract
The treatment landscape for inflammatory bowel disease (IBD) has undergone substantial advancements with the introduction of biologics. However, a considerable number of patients either show an immediate lack of response or lose responsiveness over time, necessitating the development of innovative and effective treatment approaches. Extracellular vesicles (EVs) are small lipid bilayer-enclosed structures that facilitate cell-to-cell molecular transfer and are integral to the pathogenesis of IBD. They play pivotal roles in maintaining the integrity of the intestinal epithelial barrier and the expulsion of cellular metabolites. The potential use of EVs as drug carriers or therapeutic agents has opened up a plethora of clinical applications. This review investigates the creation and content of EVs, their role in IBD development, and advances in their isolation and analytical techniques. Furthermore, the therapeutic promise they hold for IBD is explored, along with the latest research on their roles as IBD drug delivery systems.
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Affiliation(s)
- Sang Hyun Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Republic of Korea; (S.H.K.)
| | - Bora Keum
- Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Republic of Korea; (S.H.K.)
| | - Sooun Kwak
- Department of Otorhinolaryngology—Head & Neck Surgery, Korea University College of Medicine, Seoul 02841, Republic of Korea
| | - Junhyoung Byun
- Department of Otorhinolaryngology—Head & Neck Surgery, Korea University College of Medicine, Seoul 02841, Republic of Korea
- Mucosal Immunology Institute, Korea University College of Medicine, Seoul 02841, Republic of Korea
| | - Jae Min Shin
- Department of Otorhinolaryngology—Head & Neck Surgery, Korea University College of Medicine, Seoul 02841, Republic of Korea
- Mucosal Immunology Institute, Korea University College of Medicine, Seoul 02841, Republic of Korea
| | - Tae Hoon Kim
- Department of Otorhinolaryngology—Head & Neck Surgery, Korea University College of Medicine, Seoul 02841, Republic of Korea
- Mucosal Immunology Institute, Korea University College of Medicine, Seoul 02841, Republic of Korea
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Saglam-Metiner P, Duran E, Sabour-Takanlou L, Biray-Avci C, Yesil-Celiktas O. Differentiation of Neurons, Astrocytes, Oligodendrocytes and Microglia From Human Induced Pluripotent Stem Cells to Form Neural Tissue-On-Chip: A Neuroinflammation Model to Evaluate the Therapeutic Potential of Extracellular Vesicles Derived from Mesenchymal Stem Cells. Stem Cell Rev Rep 2024; 20:413-436. [PMID: 37938408 DOI: 10.1007/s12015-023-10645-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/17/2023] [Indexed: 11/09/2023]
Abstract
Advances in stem cell (SC) technology allow the generation of cellular models that recapitulate the histological, molecular and physiological properties of humanized in vitro three dimensional (3D) models, as well as production of cell-derived therapeutics such as extracellular vesicles (EVs). Improvements in organ-on-chip platforms and human induced pluripotent stem cells (hiPSCs) derived neural/glial cells provide unprecedented systems for studying 3D personalized neural tissue modeling with easy setup and fast output. Here, we highlight the key points in differentiation procedures for neurons, astrocytes, oligodendrocytes and microglia from single origin hiPSCs. Additionally, we present a well-defined humanized neural tissue-on-chip model composed of differentiated cells with the same genetic backgrounds, as well as the therapeutic potential of bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles to propose a novel treatment for neuroinflammation derived diseases. Around 100 nm CD9 + EVs promote a more anti-inflammatory and pro-remodeling of cell-cell interaction cytokine responses on tumor necrosis factor-α (TNF-α) induced neuroinflammation in neural tissue-on-chip model which is ideal for modeling authentic neural-glial patho-physiology.
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Affiliation(s)
- Pelin Saglam-Metiner
- Department of Bioengineering, Faculty of Engineering, Ege University, Izmir, Turkey
- Department of Translational Neuroscience, Division of Neuroscience, UMC Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Elif Duran
- Department of Bioengineering, Faculty of Engineering, Ege University, Izmir, Turkey
| | | | - Cigir Biray-Avci
- Department of Medical Biology, Faculty of Medicine, Ege University, Izmir, Turkey
| | - Ozlem Yesil-Celiktas
- Department of Bioengineering, Faculty of Engineering, Ege University, Izmir, Turkey.
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49
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Wu L, Gao C. Comprehensive Overview the Role of Glycosylation of Extracellular Vesicles in Cancers. ACS OMEGA 2023; 8:47380-47392. [PMID: 38144130 PMCID: PMC10734006 DOI: 10.1021/acsomega.3c07441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 11/09/2023] [Accepted: 11/15/2023] [Indexed: 12/26/2023]
Abstract
Extracellular vesicles (EVs) are membranous structures secreted by various cells carrying diverse biomolecules. Recent advancements in EV glycosylation research have underscored their crucial role in cancer. This review provides a global overview of EV glycosylation research, covering aspects such as specialized techniques for isolating and characterizing EV glycosylation, advances on how glycosylation affects the biogenesis and uptake of EVs, and the involvement of EV glycosylation in intracellular protein expression, cellular metastasis, intercellular interactions, and potential applications in immunotherapy. Furthermore, through an extensive literature review, we explore recent advances in EV glycosylation research in the context of cancer, with a focus on lung, colorectal, liver, pancreatic, breast, ovarian, prostate, and melanoma cancers. The primary objective of this review is to provide a comprehensive update for researchers, whether they are seasoned experts in the field of EVs or newcomers, aiding them in exploring new avenues and gaining a deeper understanding of EV glycosylation mechanisms. This heightened comprehension not only enhances researchers' knowledge of the pathogenic mechanisms of EV glycosylation but also paves the way for innovative cancer diagnostic and therapeutic strategies.
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Affiliation(s)
- Linlin Wu
- Department of Clinical
Laboratory
Medicine Center, Yueyang Hospital of Integrated Traditional Chinese
and Western Medicine, Shanghai University
of Traditional Chinese Medicine, Shanghai 200437, China
| | - Chunfang Gao
- Department of Clinical
Laboratory
Medicine Center, Yueyang Hospital of Integrated Traditional Chinese
and Western Medicine, Shanghai University
of Traditional Chinese Medicine, Shanghai 200437, China
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Wiedmer SK, Riekkola ML. Field-flow fractionation - an excellent tool for fractionation, isolation and/or purification of biomacromolecules. J Chromatogr A 2023; 1712:464492. [PMID: 37944435 DOI: 10.1016/j.chroma.2023.464492] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 10/30/2023] [Accepted: 11/03/2023] [Indexed: 11/12/2023]
Abstract
Field-flow fractionation (FFF) with its several variants, has developed into a mature methodology. The scope of the FFF investigations has expanded, covering both a wide range of basic studies and especially a wide range of analytical applications. Special attention of this review is given to the achievements of FFF with reference to recent applications in the fractionation, isolation, and purification of biomacromolecules, and from which especially those of (in alphabetical order) bacteria, cells, extracellular vesicles, liposomes, lipoproteins, nucleic acids, and viruses and virus-like particles. In evaluating the major approaches and trends demonstrated since 2012, the most significant biomacromolecule applications are compiled in tables. It is also evident that asymmetrical flow field-flow fractionation is by far the most dominant technique in the studies. The industry has also shown current interest in FFF and adopted it in some sophisticated fields. FFF, in combination with appropriate detectors, handles biomacromolecules in open channel in a gentle way due to the lack of shear forces and unwanted interactions caused by the stationary phase present in chromatography. In addition, in isolation and purification of biomacromolecules quite high yields can be achieved under optimal conditions.
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Affiliation(s)
- Susanne K Wiedmer
- Department of Chemistry, POB 55, 00014 University of Helsinki, Finland
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