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<!DOCTYPE html> <html lang="en" class="grade-c"> <head> <title>The physico-chemical landscape of extracellular vesicles | Nature Reviews Bioengineering</title> <link rel="alternate" type="application/rss+xml" href="https://www.nature.com/natrevbioeng.rss"/> <link rel="preconnect" href="https://cmp.nature.com" crossorigin> <meta http-equiv="X-UA-Compatible" content="IE=edge"> <meta name="applicable-device" content="pc,mobile"> <meta name="viewport" content="width=device-width,initial-scale=1.0,maximum-scale=5,user-scalable=yes"> <meta name="360-site-verification" content="5a2dc4ab3fcb9b0393241ffbbb490480" /> <script data-test="dataLayer"> window.dataLayer = [{"content":{"category":{"contentType":"review article","legacy":{"webtrendsPrimaryArticleType":"reviews","webtrendsSubjectTerms":"biologics;nanobiotechnology","webtrendsContentCategory":null,"webtrendsContentCollection":null,"webtrendsContentGroup":"Nature Reviews 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Therefore, extracellular vesicles are being explored as biomaterials, drug delivery nanocarriers, therapeutics and multiplexed biomarkers. However, the isolation, characterization and large-scale manufacturing of extracellular vesicles remains challenging. In this Review, we delineate the landscape of the physico-chemical properties of extracellular vesicles, originating from their composition and conformational ensemble, and outline how this landscape is defined by the heterogeneity of their size, composition, membrane structure, surface interactions, cargo and co-isolates. We explore the implications of this heterogeneity on the definition of the purity, identity and function of extracellular vesicles. The comparison of this landscape with the landscape of antibody therapeutics and viral vectors can identify lessons to be learned from the bioprocessing of these products, and the distinct challenges associated with the manufacturing and isolation of extracellular vesicles from biofluids, which will require new concepts and technologies. We highlight the importance of a thorough understanding of the physico-chemical properties of extracellular vesicles for their clinical translation. This includes the development of bioprocessing approaches, assignment of product quality attributes, consistency of extracellular vesicle products and manufacturing at scale. Extracellular vesicles are being explored for various biomedical applications, but face challenges with regard to isolation, characterization and manufacturing. This Review delineates the physico-chemical landscape of extracellular vesicles to identify the distinct challenges associated with the manufacturing and isolation of extracellular vesicles from biofluids and suggests opportunities to address them. \n \n \n \n \n \n \n \n \n \n \n \n \n ","datePublished":"2024-11-12T00:00:00Z","dateModified":"2024-11-12T00:00:00Z","pageStart":"1","pageEnd":"15","sameAs":"https://doi.org/10.1038/s44222-024-00255-5","keywords":["Biologics","Nanobiotechnology","Biomedical Engineering and 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The comparison of this landscape with the landscape of antibody therapeutics and viral vectors can identify lessons to be learned from the bioprocessing of these products, and the distinct challenges associated with the manufacturing and isolation of extracellular vesicles from biofluids, which will require new concepts and technologies. We highlight the importance of a thorough understanding of the physico-chemical properties of extracellular vesicles for their clinical translation. This includes the development of bioprocessing approaches, assignment of product quality attributes, consistency of extracellular vesicle products and manufacturing at scale. Extracellular vesicles are being explored for various biomedical applications, but face challenges with regard to isolation, characterization and manufacturing. 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The comparison of this landscape with the landscape of antibody therapeutics and viral vectors can identify lessons to be learned from the bioprocessing of these products, and the distinct challenges associated with the manufacturing and isolation of extracellular vesicles from biofluids, which will require new concepts and technologies. We highlight the importance of a thorough understanding of the physico-chemical properties of extracellular vesicles for their clinical translation. This includes the development of bioprocessing approaches, assignment of product quality attributes, consistency of extracellular vesicle products and manufacturing at scale. Extracellular vesicles are being explored for various biomedical applications, but face challenges with regard to isolation, characterization and manufacturing. 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id="content" data-component="article-container" data-container-type="article"> <main class="c-article-main-column u-float-left js-main-column" data-track-component="article body"> <article lang="en"> <div class="c-article-header"> <header> <ul class="c-article-identifiers" data-test="article-identifier"> <li class="c-article-identifiers__item" data-test="article-category">Review Article</li> <li class="c-article-identifiers__item">Published: <time datetime="2024-11-12">12 November 2024</time></li> </ul> <h1 class="c-article-title" data-test="article-title" data-article-title="">The physico-chemical landscape of extracellular vesicles</h1> <ul class="c-article-author-list c-article-author-list--short" data-test="authors-list" data-component-authors-activator="authors-list"><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Mauro-Manno-Aff1-Aff2" data-author-popup="auth-Mauro-Manno-Aff1-Aff2" data-author-search="Manno, Mauro">Mauro Manno</a><span class="u-js-hide"> <a class="js-orcid" href="http://orcid.org/0000-0001-9843-0428"><span class="u-visually-hidden">ORCID: </span>orcid.org/0000-0001-9843-0428</a></span><sup class="u-js-hide"><a href="#Aff1">1</a>,<a href="#Aff2">2</a></sup>, </li><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Antonella-Bongiovanni-Aff2-Aff3" data-author-popup="auth-Antonella-Bongiovanni-Aff2-Aff3" data-author-search="Bongiovanni, Antonella">Antonella Bongiovanni</a><sup class="u-js-hide"><a href="#Aff2">2</a>,<a href="#Aff3">3</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Leonid-Margolis-Aff4" data-author-popup="auth-Leonid-Margolis-Aff4" data-author-search="Margolis, Leonid">Leonid Margolis</a><sup class="u-js-hide"><a href="#Aff4">4</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Paolo-Bergese-Aff2-Aff3-Aff5-Aff6" data-author-popup="auth-Paolo-Bergese-Aff2-Aff3-Aff5-Aff6" data-author-search="Bergese, Paolo">Paolo Bergese</a><span class="u-js-hide"> <a class="js-orcid" href="http://orcid.org/0000-0002-4652-2168"><span class="u-visually-hidden">ORCID: </span>orcid.org/0000-0002-4652-2168</a></span><sup class="u-js-hide"><a href="#Aff2">2</a>,<a href="#Aff3">3</a>,<a href="#Aff5">5</a>,<a href="#Aff6">6</a></sup> & </li><li class="c-article-author-list__show-more" aria-label="Show all 5 authors for this article" title="Show all 5 authors for this article">…</li><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Paolo-Arosio-Aff7" data-author-popup="auth-Paolo-Arosio-Aff7" data-author-search="Arosio, Paolo" data-corresp-id="c1">Paolo Arosio<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-mail-medium"></use></svg></a><span class="u-js-hide"> <a class="js-orcid" href="http://orcid.org/0000-0002-2740-1205"><span class="u-visually-hidden">ORCID: </span>orcid.org/0000-0002-2740-1205</a></span><sup class="u-js-hide"><a href="#Aff7">7</a></sup> </li></ul><button aria-expanded="false" class="c-article-author-list__button"><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-down-medium"></use></svg><span>Show authors</span></button> <p class="c-article-info-details" data-container-section="info"> <a data-test="journal-link" href="/natrevbioeng" data-track="click" data-track-action="journal homepage" data-track-category="article body" data-track-label="link"><i data-test="journal-title">Nature Reviews Bioengineering</i></a> (<span data-test="article-publication-year">2024</span>)<a href="#citeas" class="c-article-info-details__cite-as u-hide-print" data-track="click" data-track-action="cite this article" data-track-label="link">Cite this article</a> </p> <div class="c-article-metrics-bar__wrapper u-clear-both"> <ul class="c-article-metrics-bar u-list-reset"> <li class=" c-article-metrics-bar__item" data-test="access-count"> <p class="c-article-metrics-bar__count">474 <span class="c-article-metrics-bar__label">Accesses</span></p> </li> <li class="c-article-metrics-bar__item" data-test="altmetric-score"> <p class="c-article-metrics-bar__count">7 <span class="c-article-metrics-bar__label">Altmetric</span></p> </li> <li class="c-article-metrics-bar__item"> <p class="c-article-metrics-bar__details"><a href="/articles/s44222-024-00255-5/metrics" data-track="click" data-track-action="view metrics" data-track-label="link" rel="nofollow">Metrics <span class="u-visually-hidden">details</span></a></p> </li> </ul> </div> </header> <div class="u-js-hide" data-component="article-subject-links"> <h3 class="c-article__sub-heading">Subjects</h3> <ul class="c-article-subject-list"> <li class="c-article-subject-list__subject"><a href="/subjects/biologics" data-track="click" data-track-action="view subject" data-track-label="link">Biologics</a></li><li class="c-article-subject-list__subject"><a href="/subjects/nanobiotechnology" data-track="click" data-track-action="view subject" data-track-label="link">Nanobiotechnology</a></li> </ul> </div> </div> <div class="c-article-body"> <section aria-labelledby="Abs1" data-title="Abstract" lang="en"><div class="c-article-section" id="Abs1-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Abs1">Abstract</h2><div class="c-article-section__content" id="Abs1-content"><p>Extracellular vesicles are defined as nanosized to microsized particles, delimited by a lipid bilayer membrane, that seem to be released by all cell types and that can transport bioactive molecules between cells, tissues, organs and organisms. Therefore, extracellular vesicles are being explored as biomaterials, drug delivery nanocarriers, therapeutics and multiplexed biomarkers. However, the isolation, characterization and large-scale manufacturing of extracellular vesicles remains challenging. In this Review, we delineate the landscape of the physico-chemical properties of extracellular vesicles, originating from their composition and conformational ensemble, and outline how this landscape is defined by the heterogeneity of their size, composition, membrane structure, surface interactions, cargo and co-isolates. We explore the implications of this heterogeneity on the definition of the purity, identity and function of extracellular vesicles. The comparison of this landscape with the landscape of antibody therapeutics and viral vectors can identify lessons to be learned from the bioprocessing of these products, and the distinct challenges associated with the manufacturing and isolation of extracellular vesicles from biofluids, which will require new concepts and technologies. We highlight the importance of a thorough understanding of the physico-chemical properties of extracellular vesicles for their clinical translation. This includes the development of bioprocessing approaches, assignment of product quality attributes, consistency of extracellular vesicle products and manufacturing at scale.</p></div></div></section><section aria-labelledby="Abs3" data-title="Key points" lang="en"><div class="c-article-section" id="Abs3-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Abs3">Key points</h2><div class="c-article-section__content" id="Abs3-content"><ul class="u-list-style-bullet"> <li> <p>The complexity of the physico-chemical landscape of extracellular vesicles exceeds that of protein biologics and viral vectors, thus complicating the definition of extracellular vesicle identity and purity.</p> </li> <li> <p>Extracellular vesicle populations may be viewed as a continuum of vesicle structures.</p> </li> <li> <p>The physico-chemical landscape of extracellular vesicles can inform approaches for their isolation, characterization and large-scale manufacturing.</p> </li> <li> <p>New and standardized technologies are required for the clinical translation of extracellular vesicles as marketable products.</p> </li> </ul></div></div></section> <noscript> <div class="c-nature-box c-nature-box--side " data-component="entitlement-box"> <div class="js-access-button"> <a href="https://wayf.springernature.com?redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs44222-024-00255-5" class="c-article__button" data-test="ra21"> <svg class="u-icon" width="18" height="18" aria-hidden="true" focusable="false"><use href="#icon-institution"></use></svg> <span class="c-article__button-text">Access through your institution</span> </a> </div> <div class="js-buy-button"> <a href="#access-options" class="c-article__button c-article__button--inverted" data-test="ra21"> <span>Buy or subscribe</span> </a> </div> </div> </noscript> <div class="js-context-bar-sticky-point-mobile" data-track-context="article body"> </div> <div 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CN00000041 CN3 RNA); and by the ‘European Brain ReseArch INfrastructureS-Italy’ (EBRAINS-Italy, project code IR0000011) funded by the European Union — NextGenerationEU under the National Recovery and Resilience Plan (NRRP), Concession Decree No. 117 of 21 June 2022 adopted by the Italian Ministry of University and Research. The authors acknowledge L. Paolini, M. Romano, A. Zendrini and C. Paganini for their critical reading and A. Paganini for assistance with the illustrations.</p></div></div></section><section aria-labelledby="author-information" data-title="Author information"><div class="c-article-section" id="author-information-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="author-information">Author information</h2><div class="c-article-section__content" id="author-information-content"><h3 class="c-article__sub-heading" id="affiliations">Authors and Affiliations</h3><ol class="c-article-author-affiliation__list"><li id="Aff1"><p class="c-article-author-affiliation__address">Institute of Biophysics, National Research Council, Palermo, Italy</p><p class="c-article-author-affiliation__authors-list">Mauro Manno</p></li><li id="Aff2"><p class="c-article-author-affiliation__address">National Center for Gene Therapy and Drugs based on RNA Technology, Padova, Italy</p><p class="c-article-author-affiliation__authors-list">Mauro Manno, Antonella Bongiovanni & Paolo Bergese</p></li><li id="Aff3"><p class="c-article-author-affiliation__address">Institute for Research and Biomedical Innovation (IRIB), National Research Council, Palermo, Italy</p><p class="c-article-author-affiliation__authors-list">Antonella Bongiovanni & Paolo Bergese</p></li><li id="Aff4"><p class="c-article-author-affiliation__address">Faculty of Natural Sciences and Medicine, Ilia State University, Tbilisi, Republic of Georgia</p><p class="c-article-author-affiliation__authors-list">Leonid Margolis</p></li><li id="Aff5"><p class="c-article-author-affiliation__address">Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy</p><p class="c-article-author-affiliation__authors-list">Paolo Bergese</p></li><li id="Aff6"><p class="c-article-author-affiliation__address">Center for Colloid and Surface Science (CSGI), Florence, Italy</p><p class="c-article-author-affiliation__authors-list">Paolo Bergese</p></li><li id="Aff7"><p class="c-article-author-affiliation__address">Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland</p><p class="c-article-author-affiliation__authors-list">Paolo Arosio</p></li></ol><div class="u-js-hide u-hide-print" data-test="author-info"><span class="c-article__sub-heading">Authors</span><ol class="c-article-authors-search u-list-reset"><li id="auth-Mauro-Manno-Aff1-Aff2"><span class="c-article-authors-search__title u-h3 js-search-name">Mauro Manno</span><div class="c-article-authors-search__list"><div class="c-article-authors-search__item c-article-authors-search__list-item--left"><a href="/search?author=Mauro%20Manno" class="c-article-button" data-track="click" data-track-action="author link - 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id="citeas">Cite this article</h3><p class="c-bibliographic-information__citation">Manno, M., Bongiovanni, A., Margolis, L. <i>et al.</i> The physico-chemical landscape of extracellular vesicles. <i>Nat Rev Bioeng</i> (2024). https://doi.org/10.1038/s44222-024-00255-5</p><p class="c-bibliographic-information__download-citation u-hide-print"><a data-test="citation-link" data-track="click" data-track-action="download article citation" data-track-label="link" data-track-external="" rel="nofollow" href="https://citation-needed.springer.com/v2/references/10.1038/s44222-024-00255-5?format=refman&flavour=citation">Download citation<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-download-medium"></use></svg></a></p><ul class="c-bibliographic-information__list" data-test="publication-history"><li class="c-bibliographic-information__list-item"><p>Accepted<span class="u-hide">: 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