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Entry and exit of extracellular vesicles to and from the blood circulation

Nature Nanotechnology volume 19, pages 13–20 (2024)Cite this article

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Abstract

Extracellular vesicles (EVs) are biological nanoparticles that promote intercellular communication by delivering bioactive cargo over short and long distances. Short-distance communication takes place in the interstitium, whereas long-distance communication is thought to require transport through the blood circulation to reach distal sites. Extracellular vesicle therapeutics are frequently injected systemically, and diagnostic approaches often rely on the detection of organ-derived EVs in the blood. However, the mechanisms by which EVs enter and exit the circulation are poorly understood. Here, the lymphatic system and transport across the endothelial barrier through paracellular and transcellular routes are discussed as potential pathways for EV entry to and exit from the blood circulatory system.

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Fig. 1: Potential pathways of EV entry to and exit from the blood circulation.
Fig. 2: Mechanisms for cancer cell-derived EVs to cross the blood–brain barrier endothelium.
Fig. 3: Potential pathways of EV entry into the blood circulation through the lymphatic system.

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Acknowledgements

Partial funding for this work was provided by The University of Queensland, Australia (J.W.), the National Institute on Aging, National Institutes of Health, United States under award number R01AG076537 (J.W.) and The Medical Research Future Fund, Australia under award number MRF2019485 (J.W.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the organizations and funding agencies.

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  1. These authors contributed equally: Dalila Iannotta, Amruta A.

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  1. School of Chemical Engineering, The University of Queensland, Brisbane, Queensland, Australia

    Dalila Iannotta, Amruta A & Joy Wolfram

  2. Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, Australia

    Amanda W. Kijas, Alan E. Rowan & Joy Wolfram

  3. Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA

    Joy Wolfram

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Iannotta, D., A, A., Kijas, A.W. et al. Entry and exit of extracellular vesicles to and from the blood circulation. Nat. Nanotechnol. 19, 13–20 (2024). https://doi.org/10.1038/s41565-023-01522-z

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