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The status of extracellular vesicles as drug carriers and therapeutics

Nature Reviews Bioengineering (2026)Cite this article

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Abstract

Owing to their natural origin and biocompatibility, extracellular vesicles (EVs) are being recognized as next-generation vehicles for targeted drug delivery. Despite their potential as therapeutic carriers, EVs suffer from heterogeneity, low yields, limited cargo loading efficiency and rapid clearance by the mononuclear phagocyte system. Since the first EV-based clinical trial in 2005, more than 100 clinical trials have investigated the use of EVs as therapeutics and drug carriers. Despite this, no EV-based therapies have received regulatory approval to date. This gap between preclinical research activity and clinical translation underscores persistent scientific challenges and regulatory hurdles that continue to impede the advancement of EV-based therapeutics. In this Review, we examine the research articles published in the field between 2012 and 2024 (38,177 articles), highlighting key developments, persistent challenges and evolving assumptions. We review the current EV landscape and clinical trials, focusing on their organotropism and use as carriers for therapeutics. We compare their advantages and limitations in relation to other nanoparticles, such as lipid nanoparticles and liposomes, and examine how labelling strategies and cell sources influence EV biodistribution. Finally, we outline translational considerations for EV-based therapeutics and propose additional reporting standards, complementing the MISEV 2023 guidelines.

Key points

  • Extracellular vesicles (EVs) have emerged as promising drug carriers owing to their biocompatibility, stability and ability to transport a wide range of molecular cargo.

  • Most current clinical studies focus on the intrinsic therapeutic potential of EVs, with only about 5% incorporating exogenous drugs.

  • Of the articles reporting EV-mediated small interfering RNA delivery, 87% do not report dose–response curves, which are essential for evaluating therapeutic efficacy, ensuring pharmacological specificity and enabling comparisons across studies.

  • The cell source of intravenously administered EVs minimally influences organ targeting, with most accumulating primarily in organs of the mononuclear phagocyte system.

  • Tumour-derived and non-tumour-derived EVs show similar tumour accumulation in biodistribution studies, suggesting that passive mechanisms, such as the enhanced permeability and retention effect, might be responsible.

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Fig. 1: Preclinical research on extracellular vesicles.
Fig. 2: Clinical research on therapeutic EVs.
Fig. 3: EVs as drug carriers.
Fig. 4: In vivo biodistribution of EVs in murine models.
Fig. 5: In vivo biodistribution of EVs derived from different cell sources.

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Acknowledgements

We acknowledge funding from the NIH through grants R01GM150252 and R01HL174038, which supported this work. A.P.C. acknowledges the funding support from the Predoctoral Fellowship in Drug Delivery from the PhRMA Foundation. The authors gratefully acknowledge H. Oh for her support in organizing some of the initial data from the literature that contributed to sections of this Review. The authors acknowledge the use of Copilot for assistance with improving language clarity in selected portions of the manuscript.

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Authors and Affiliations

  1. Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Ameya P. Chaudhari, Omar M. Budayr, Emily E. Bonacquisti, Caden C. Kussatz, Mark S. Bannon, Karissa J. Law, Leaf Huang & Juliane Nguyen

  2. Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Karissa J. Law

  3. Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Yusha Liu

  4. Department of Systems and Information Engineering, University of Virginia, Charlottesville, VA, USA

    Matthew L. Bolton

  5. Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, Philadelphia, PA, USA

    Patrick M. Glassman

  6. Lampe Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Juliane Nguyen

  7. UNC McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Juliane Nguyen

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  1. Ameya P. Chaudhari
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Contributions

A.P.C., E.E.B. and J.N. conceptualized the work. A.P.C., O.M.B., E.E.B., C.C.K., M.S.B. and K.J.L. extracted data from articles to compile the source dataset. A.P.C., Y.L., M.L.B., P.M.G. and J.N. analysed the data. A.P.C., O.M.B. and J.N. wrote the manuscript. A.P.C., O.M.B., L.H. and J.N. edited and revised the manuscript. J.N. provided resources and supervision.

Corresponding author

Correspondence to Juliane Nguyen.

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Competing interests

J.N. is an inventor on the patent applications of the EXO-Code technology that is cited in this Review. The technology has been licensed to Exopharm. These relationships have been disclosed to and are under management by UNC-Chapel Hill.

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Nature Reviews Bioengineering thanks Ke Cheng, Yvonne Couch and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Chaudhari, A.P., Budayr, O.M., Bonacquisti, E.E. et al. The status of extracellular vesicles as drug carriers and therapeutics. Nat Rev Bioeng (2026). https://doi.org/10.1038/s44222-026-00405-x

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