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      Extracellular vesicles: a rising star for therapeutics and drug delivery

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          Abstract

          Extracellular vesicles (EVs) are nano-sized, natural, cell-derived vesicles that contain the same nucleic acids, proteins, and lipids as their source cells. Thus, they can serve as natural carriers for therapeutic agents and drugs, and have many advantages over conventional nanocarriers, including their low immunogenicity, good biocompatibility, natural blood brain barrier penetration, and capacity for gene delivery. This review first introduces the classification of EVs and then discusses several currently popular methods for isolating and purifying EVs, EVs-mediated drug delivery, and the functionalization of EVs as carriers. Thereby, it provides new avenues for the development of EVs-based therapeutic strategies in different fields of medicine. Finally, it highlights some challenges and future perspectives with regard to the clinical application of EVs.

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          Highlights

          • Various current techniques for isolating extracellular vesicles are reviewed, and their advantages and disadvantages are compared.

          • An overview of the strategies used for the modification of extracellular vesicles and their application as delivery systems or therapeutic agents in different diseases is provided.

          • Several challenges in the clinical application of extracellular vesicles-based nanoplatforms are discussed, along with solutions for their implementation as a promising therapeutic tool.

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          Most cited references263

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          The biology, function, and biomedical applications of exosomes

          The study of extracellular vesicles (EVs) has the potential to identify unknown cellular and molecular mechanisms in intercellular communication and in organ homeostasis and disease. Exosomes, with an average diameter of ~100 nanometers, are a subset of EVs. The biogenesis of exosomes involves their origin in endosomes, and subsequent interactions with other intracellular vesicles and organelles generate the final content of the exosomes. Their diverse constituents include nucleic acids, proteins, lipids, amino acids, and metabolites, which can reflect their cell of origin. In various diseases, exosomes offer a window into altered cellular or tissue states, and their detection in biological fluids potentially offers a multicomponent diagnostic readout. The efficient exchange of cellular components through exosomes can inform their applied use in designing exosome-based therapeutics.
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            Shedding light on the cell biology of extracellular vesicles

            Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising exosomes and microvesicles, which originate from the endosomal system or which are shed from the plasma membrane, respectively. They are present in biological fluids and are involved in multiple physiological and pathological processes. Extracellular vesicles are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material. Knowledge of the cellular processes that govern extracellular vesicle biology is essential to shed light on the physiological and pathological functions of these vesicles as well as on clinical applications involving their use and/or analysis. However, in this expanding field, much remains unknown regarding the origin, biogenesis, secretion, targeting and fate of these vesicles.
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              Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication

              The ability of exosomes to transfer cargo from donor to acceptor cells, thereby triggering phenotypic changes in the latter, has generated substantial interest in the scientific community. However, the extent to which exosomes differ from other extracellular vesicles in terms of their biogenesis and functions remains ill-defined. Here, we discuss the current knowledge on the specificities of exosomes and other types of extracellular vesicles, and their roles as important agents of cell-to-cell communication.
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                Author and article information

                Contributors
                lrao@szbl.ac.cn
                xiaojiachen@um.edu.mo
                chentongkai@gzucm.edu.cn
                Journal
                J Nanobiotechnology
                J Nanobiotechnology
                Journal of Nanobiotechnology
                BioMed Central (London )
                1477-3155
                20 July 2023
                20 July 2023
                2023
                : 21
                : 231
                Affiliations
                [1 ]GRID grid.411866.c, ISNI 0000 0000 8848 7685, Science and Technology Innovation Center, , Guangzhou University of Chinese Medicine, ; 12 Jichang Road, Guangzhou, 510405 China
                [2 ]GRID grid.437123.0, ISNI 0000 0004 1794 8068, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, , University of Macau, ; Room 6007, N22, Taipa, 999078 Macau SAR China
                [3 ]GRID grid.510951.9, ISNI 0000 0004 7775 6738, Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, ; Shenzhen, 518132 China
                Article
                1973
                10.1186/s12951-023-01973-5
                10360328
                37475025
                af8c2c8c-0860-4619-a5f5-95135b1dc4ca
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 3 March 2023
                : 29 June 2023
                Funding
                Funded by: Key Fields of Biomedicine and Health Foundation of Colleges and Universities
                Award ID: 2022ZDZX2017
                Award Recipient :
                Funded by: Guangdong Basic and Applied Basic Research Foundation
                Award ID: 2022A1515012154
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100021171, Basic and Applied Basic Research Foundation of Guangdong Province;
                Award ID: 2019B1515120043
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: File no. 82104354
                Award Recipient :
                Funded by: the Science and Technology Development Fund, Macau SAR
                Award ID: File no. 0070/2021/AGJ
                Award Recipient :
                Funded by: University of Macau
                Award ID: File no. MYRG2022-00198-ICMS
                Award Recipient :
                Categories
                Review
                Custom metadata
                © BioMed Central Ltd., part of Springer Nature 2023

                Biotechnology
                extracellular vesicles,drug loading,surface modification,targeted therapy,neurodegenerative diseases,clinical challenges

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