The status of extracellular vesicles as drug carriers and therapeutics

Posted on
the-status-of-extracellular-vesicles-as-drug-carriers-and-therapeutics
The status of extracellular vesicles as drug carriers and therapeutics

References

  1. Jeppesen, D. K., Zhang, Q., Franklin, J. L. & Coffey, R. J. Extracellular vesicles and nanoparticles: emerging complexities. Trends Cell Biol. 33, 667–681 (2023).

    Article  Google Scholar 

  2. Kishore, R. & Khan, M. More than tiny sacks: stem cell exosomes as cell-free modality for cardiac repair. Circ. Res. 118, 330–343 (2016).

    Article  Google Scholar 

  3. Mulcahy, L. A., Pink, R. C. & Carter, D. R. F. Routes and mechanisms of extracellular vesicle uptake. J. Extracell. Vesicles 3, 24641 (2014).

    Article  Google Scholar 

  4. Dai, J. et al. Exosomes: key players in cancer and potential therapeutic strategy. Signal Transduct. Target. Ther. 5, 145 (2020).

    Article  Google Scholar 

  5. Stahl, P. D. & Raposo, G. Extracellular vesicles: exosomes and microvesicles, integrators of homeostasis. Physiology 34, 169–177 (2019).

    Article  Google Scholar 

  6. Ferguson, S. W. & Nguyen, J. Exosomes as therapeutics: the implications of molecular composition and exosomal heterogeneity. J. Control. Release 228, 179–190 (2016).

    Article  Google Scholar 

  7. Liang, Y., Duan, L., Lu, J. & Xia, J. Engineering exosomes for targeted drug delivery. Theranostics 11, 3183–3195 (2021).

    Article  Google Scholar 

  8. Bonacquisti, R. Engineering a genetically-encodable toolkit for tracking extracellular vesicle RNA cargo. PhD thesis, Univ. North Carolina Chapel Hill (2023).

  9. Liang, X. et al. Engineering of extracellular vesicles for efficient intracellular delivery of multimodal therapeutics including genome editors. Nat. Commun. 16, 4028 (2025).

    Article  Google Scholar 

  10. Wiklander, O. P. B. et al. Antibody-displaying extracellular vesicles for targeted cancer therapy. Nat. Biomed. Eng. 8, 1453–1468 (2024).

    Article  Google Scholar 

  11. Zhang, T., Zhang, L., Ma, X. & Song, W. The tiny giants of regeneration: MSC-derived extracellular vesicles as next-generation therapeutics. Front. Cell Dev. Biol. 13, 1612589 (2025).

    Article  Google Scholar 

  12. Nguyen, J. & Fuhrmann, G. Extracellular vesicles — a versatile biomaterial. Adv. Healthc. Mater. 11, e2200192 (2022).

    Article  Google Scholar 

  13. Delen, M. V., Derdelinckx, J., Wouters, K., Nelissen, I. & Cools, N. A systematic review and meta-analysis of clinical trials assessing safety and efficacy of human extracellular vesicle-based therapy. J. Extracell. Vesicles 13, e12458 (2024).

    Article  Google Scholar 

  14. Fraiman, J. et al. Serious adverse events of special interest following mRNA COVID-19 vaccination in randomized trials in adults. Vaccine 40, 5798–5805 (2022).

    Article  Google Scholar 

  15. Murphy, D. E. et al. Natural or synthetic RNA Delivery: a stoichiometric comparison of extracellular vesicles and synthetic nanoparticles. Nano Lett. 21, 1888–1895 (2021).

    Article  Google Scholar 

  16. Kang, M., Jordan, V., Blenkiron, C. & Chamley, L. W. Biodistribution of extracellular vesicles following administration into animals: a systematic review. J. Extracell. Vesicles 10, e12085 (2021).

    Article  Google Scholar 

  17. Anderson, J. D. et al. Comprehensive proteomic analysis of mesenchymal stem cell exosomes reveals modulation of angiogenesis via nuclear factor-kappaB signaling. Stem Cell 34, 601–613 (2016).

    Article  Google Scholar 

  18. Ferguson, S. W. et al. The microRNA regulatory landscape of MSC-derived exosomes: a systems view. Sci. Rep. 8, 1419 (2018).

    Article  Google Scholar 

  19. Chansoria, P. et al. Instantly adhesive and ultra-elastic patches for dynamic organ and wound repair. Nat. Commun. 15, 4720 (2024).

    Article  Google Scholar 

  20. Hatzistergos, K. E., Blum, A., Ince, T., Grichnik, J. & Hare, J. M. What is the oncologic risk of stem cell treatment for heart disease? Circ. Res. 108, 1300–1303 (2011).

    Article  Google Scholar 

  21. Chiangjong, W., Netsirisawan, P., Hongeng, S. & Chutipongtanate, S. Red blood cell extracellular vesicle-based drug delivery: challenges and opportunities. Front. Med. 8, 761362 (2021).

    Article  Google Scholar 

  22. Biagiotti, S. et al. Efficient and highly reproducible production of red blood cell-derived extracellular vesicle mimetics for the loading and delivery of RNA molecules. Sci. Rep. 14, 14610 (2024).

    Article  Google Scholar 

  23. Usman, W. M. et al. Efficient RNA drug delivery using red blood cell extracellular vesicles. Nat. Commun. 9, 2359 (2018).

    Article  Google Scholar 

  24. Zhang, G. et al. Extracellular vesicles: natural liver-accumulating drug delivery vehicles for the treatment of liver diseases. J. Extracell. Vesicle 10, e12030 (2020).

    Article  Google Scholar 

  25. Wu, J., Piao, Y., Liu, Q. & Yang, X. Platelet-rich plasma-derived extracellular vesicles: a superior alternative in regenerative medicine? Cell Prolif. 54, e13123 (2021).

    Article  Google Scholar 

  26. Antich-Rosselló, M. et al. Platelet-derived extracellular vesicles for regenerative medicine. Int. J. Mol. Sci. 22, 8580 (2021).

    Article  Google Scholar 

  27. Wang, Z., Wang, Q., Qin, F. & Chen, J. Exosomes: a promising avenue for cancer diagnosis beyond treatment. Front. Cell Dev. Biol. 12, 1344705 (2024).

    Article  Google Scholar 

  28. Wang, X. et al. Exosomes and cancer — diagnostic and prognostic biomarkers and therapeutic vehicle. Oncogenesis 11, 54 (2022).

    Article  Google Scholar 

  29. McNamara, R. P. et al. Exosome-encased nucleic acid scaffold chemotherapeutic agents for superior anti-tumor and anti-angiogenesis activity. ACS Bio Med Chem Au 2, 140–149 (2022).

    Article  Google Scholar 

  30. Nguyen, V. D., Kim, H. Y., Choi, Y. H., Park, J.-O. & Choi, E. Tumor-derived extracellular vesicles for the active targeting and effective treatment of colorectal tumors in vivo. Drug Deliv. 29, 2621–2631 (2022).

    Article  Google Scholar 

  31. Feng, L., Guo, L., Tanaka, Y. & Su, L. Tumor-derived small extracellular vesicles involved in breast cancer progression and drug resistance. Int. J. Mol. Sci. 23, 15236 (2022).

    Article  Google Scholar 

  32. Guo, X., Sui, R. & Piao, H. Tumor-derived small extracellular vesicles: potential roles and mechanism in glioma. J. Nanobiotechnol. 20, 383 (2022).

    Article  Google Scholar 

  33. Haney, M. J. et al. Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J. Control. Release 207, 18–30 (2015).

    Article  Google Scholar 

  34. Yuan, D. et al. Macrophage exosomes as natural nanocarriers for protein delivery to inflamed brain. Biomaterials 142, 1–12 (2017).

    Article  Google Scholar 

  35. Aiello, S. et al. Extracellular vesicles derived from T regulatory cells suppress T cell proliferation and prolong allograft survival. Sci. Rep. 7, 11518 (2017).

    Article  Google Scholar 

  36. Fernández-Messina, L., Gutiérrez-Vázquez, C., Rivas-García, E., Sánchez-Madrid, F. & de la Fuente, H. Immunomodulatory role of microRNAs transferred by extracellular vesicles. Biol. Cell 107, 61–77 (2015).

    Article  Google Scholar 

  37. Kim, M. S. et al. Engineering macrophage-derived exosomes for targeted paclitaxel delivery to pulmonary metastases: in vitro and in vivo evaluations. Nanomedicine 14, 195–204 (2018).

    Article  Google Scholar 

  38. Williams, A. et al. Targeting of extracellular vesicle-based therapeutics to the brain. Cell 14, 548 (2025).

    Article  Google Scholar 

  39. Cheng, L., Wang, Y. & Huang, L. Exosomes from M1-polarized macrophages potentiate the cancer vaccine by creating a pro-inflammatory microenvironment in the lymph node. Mol. Ther. 25, 1665–1675 (2017).

    Article  Google Scholar 

  40. Tan, E., Chin, C. S. H., Lim, Z. F. S. & Ng, S. K. HEK293 cell line as a platform to produce recombinant proteins and viral vectors. Front. Bioeng. Biotechnol. 9, 796991 (2021).

    Article  Google Scholar 

  41. Ohno, S.-I. et al. Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol. Ther. 21, 185–191 (2013).

    Article  Google Scholar 

  42. Wang, C. et al. Engineering a HEK-293T exosome-based delivery platform for efficient tumor-targeting chemotherapy/internal irradiation combination therapy. J. Nanobiotechnol. 20, 247 (2022).

    Article  Google Scholar 

  43. Sung, B. H. et al. A live cell reporter of exosome secretion and uptake reveals pathfinding behavior of migrating cells. Nat. Commun. 11, 2092 (2020).

    Article  Google Scholar 

  44. Tieu, A. et al. Biodistribution of mesenchymal stromal cell-derived extracellular vesicles administered during acute lung injury. Stem Cell Res. Ther. 14, 250 (2023).

    Article  Google Scholar 

  45. Kronstadt, S. M., Heyningen, L. H. V., Aranda, A. & Jay, S. M. Assessment of anti-inflammatory bioactivity of extracellular vesicles is susceptible to error via media component contamination. Cytotherapy 25, 387–396 (2023).

    Article  Google Scholar 

  46. Zhu, X. et al. Comprehensive toxicity and immunogenicity studies reveal minimal effects in mice following sustained dosing of extracellular vesicles derived from HEK293T cells. J. Extracell. Vesicles 6, 1324730 (2017).

    Article  Google Scholar 

  47. Saleh, A. F. et al. Extracellular vesicles induce minimal hepatotoxicity and immunogenicity. Nanoscale 11, 6990–7001 (2019).

    Article  Google Scholar 

  48. Ferguson, S., Kim, S., Lee, C., Deci, M. & Nguyen, J. The phenotypic effects of exosomes secreted from distinct cellular sources: a comparative study based on miRNA composition. AAPS J. 20, 67 (2018).

    Article  Google Scholar 

  49. Hagey, D. W. et al. The cellular response to extracellular vesicles is dependent on their cell source and dose. Sci. Adv. 9, eadh1168 (2023).

    Article  Google Scholar 

  50. Escudier, B. et al. Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial. J. Transl. Med. 3, 10 (2005).

    Article  Google Scholar 

  51. Maxson, S., Lopez, E. A., Yoo, D., Danilkovitch-Miagkova, A. & LeRoux, M. A. Concise Review: role of mesenchymal stem cells in wound repair. Stem Cell Transl. Med. 1, 142–149 (2012).

    Article  Google Scholar 

  52. Wang, J. et al. Boosting the biogenesis and secretion of mesenchymal stem cell-derived exosomes. Cell 9, 660 (2020).

    Article  Google Scholar 

  53. Wang, J. et al. MiR-101a loaded extracellular nanovesicles as bioactive carriers for cardiac repair. Nanomedicine 27, 102201 (2020).

    Article  Google Scholar 

  54. Jasiewicz, N. E. et al. In situ-crosslinked Zippersomes enhance cardiac repair by increasing accumulation and retention. Bioeng. Transl. Med. 9, e10697 (2024).

    Article  Google Scholar 

  55. Zhang, K. & Cheng, K. Stem cell-derived exosome versus stem cell therapy. Nat. Rev. Bioeng. 1, 608–609 (2023).

    Article  Google Scholar 

  56. Popowski, K. D. et al. Inhalable dry powder mRNA vaccines based on extracellular vesicles. Matter 5, 2960–2974 (2022).

    Article  Google Scholar 

  57. Carney, R. P. et al. Harnessing extracellular vesicle heterogeneity for diagnostic and therapeutic applications. Nat. Nanotechnol. 20, 14–25 (2024).

    Article  Google Scholar 

  58. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT04493242 (2024).

  59. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT04491240 (2020).

  60. Margiana, R. et al. Clinical application of mesenchymal stem cell in regenerative medicine: a narrative review. Stem Cell Res. Ther. 13, 366 (2022).

    Article  Google Scholar 

  61. Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663–676 (2006).

    Article  Google Scholar 

  62. Takahashi, K. et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861–872 (2007).

    Article  Google Scholar 

  63. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT05523011 (2024).

  64. Chandran, N. S. et al. A phase 1, open-label study to determine safety and tolerability of the topical application of mesenchymal stem/stromal cell (MSC) exosome ointment to treat psoriasis in healthy volunteers. Cytotherapy 27, 633–641 (2025).

    Article  Google Scholar 

  65. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT03608631 (2025).

  66. Kamerkar, S. et al. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature 546, 498–503 (2017).

    Article  Google Scholar 

  67. Surana, R. et al. Phase I study of mesenchymal stem cell (MSC)-derived exosomes with KRASG12D siRNA in patients with metastatic pancreatic cancer harboring a KRASG12D mutation. J. Clin. Oncol. 40, TPS633 (2022).

    Article  Google Scholar 

  68. Mendt, M. et al. Generation and testing of clinical-grade exosomes for pancreatic cancer. JCI Insight 3, e99263 (2018).

    Article  Google Scholar 

  69. Kalluri, V. S. et al. Engineered exosomes with KrasG12D specific siRNA in pancreatic cancer: a phase I study with immunological correlates. Nat. Commun. 16, 8696 (2025).

    Article  Google Scholar 

  70. Yang, Y. et al. Acquisition of new tumor cell properties by MSC-derived exosomes. Int. J. Oncol. 47, 244–252 (2015).

    Article  Google Scholar 

  71. Roccaro, A. M. et al. BM mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression. J. Clin. Invest. 123, 1542–1555 (2013).

    Article  Google Scholar 

  72. Zhu, W. et al. Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo. Cancer Lett. 315, 28–37 (2012).

    Article  Google Scholar 

  73. Wang, J. et al. Mesenchymal stem cell-derived extracellular vesicles alter disease outcomes via endorsement of macrophage polarization. Stem Cell Res. Ther. 11, 424 (2020).

    Article  Google Scholar 

  74. Zhao, R., Chen, X., Song, H., Bie, Q. & Zhang, B. Dual role of MSC-derived exosomes in tumor development. Stem Cell Int. 2020, 8844730 (2020).

    Google Scholar 

  75. Adlerz, K., Patel, D., Rowley, J., Ng, K. & Ahsan, T. Strategies for scalable manufacturing and translation of MSC-derived extracellular vesicles. Stem Cell Res. 48, 101978 (2020).

    Article  Google Scholar 

  76. Xia, Y., Zhang, J., Liu, G. & Wolfram, J. Immunogenicity of extracellular vesicles. Adv. Mater. 36, 2403199 (2024).

    Article  Google Scholar 

  77. Zeng, F. et al. Graft-derived extracellular vesicles transported across subcapsular sinus macrophages elicit B cell alloimmunity after transplantation. Sci. Transl. Med. 13, eabb0122 (2021).

    Article  Google Scholar 

  78. Labusek, N. et al. Extracellular vesicles from immortalized mesenchymal stromal cells protect against neonatal hypoxic-ischemic brain injury. Inflamm. Regen. 43, 24 (2023).

    Article  Google Scholar 

  79. Shitova, M., Alpeeva, E. & Vorotelyak, E. Review of hTERT-immortalized cells: how to assess immortality and confirm identity. Int. J. Mol. Sci. 25, 13054 (2024).

    Article  Google Scholar 

  80. Lin, Y. C. et al. Genome dynamics of the human embryonic kidney 293 lineage in response to cell biology manipulations. Nat. Commun. 5, 4767 (2014).

    Article  Google Scholar 

  81. Lilyestrom, W., Klein, M. G., Zhang, R., Joachimiak, A. & Chen, X. S. Crystal structure of SV40 large T-antigen bound to p53: interplay between a viral oncoprotein and a cellular tumor suppressor. Genes Dev. 20, 2373–2382 (2006).

    Article  Google Scholar 

  82. US National Library of Medicine. ClinicalTrials.gov https://www.clinicaltrials.gov/study/NCT05216562 (2022).

  83. Gonzalez-King, H. et al. Hypoxia inducible factor-1α potentiates jagged 1-mediated angiogenesis by mesenchymal stem cell-derived exosomes. Stem Cell 35, 1747–1759 (2017).

    Article  Google Scholar 

  84. Arslan, F. et al. Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury. Stem Cell Res. 10, 301–312 (2013).

    Article  Google Scholar 

  85. Jasiewicz, N., Drabenstott, C. & Nguyen, J. Harnessing the full potential of extracellular vesicles as drug carriers. Curr. Opin. Colloid Interface Sci. 51, 101412 (2021).

    Article  Google Scholar 

  86. Bader, J., Brigger, F. & Leroux, J.-C. Extracellular vesicles versus lipid nanoparticles for the delivery of nucleic acids. Adv. Drug Deliv. Rev. 215, 115461 (2024).

    Article  Google Scholar 

  87. Zeng, H. et al. Current strategies for exosome cargo loading and targeting delivery. Cells 12, 1416 (2023).

    Article  Google Scholar 

  88. Luan, X. et al. Engineering exosomes as refined biological nanoplatforms for drug delivery. Acta Pharmacol. Sin. 38, 754–763 (2017).

    Article  Google Scholar 

  89. Liu, M. et al. Inhalable extracellular vesicle delivery of IL-12 mRNA to treat lung cancer and promote systemic immunity. Nat. Nanotechnol. 19, 565–575 (2024).

    Article  Google Scholar 

  90. Kim, M. S. et al. Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomedicine 12, 655–664 (2016).

    Article  Google Scholar 

  91. Le Saux, S. et al. Post-production modifications of murine mesenchymal stem cell (mMSC) derived extracellular vesicles (EVs) and impact on their cellular interaction. Biomaterials 231, 119675 (2020).

    Article  Google Scholar 

  92. Nizamudeen, Z. A. et al. Low-power sonication can alter extracellular vesicle size and properties. Cells 10, 2413 (2021).

    Article  Google Scholar 

  93. Chen, W. Electroconformational denaturation of membrane proteins. Ann. N. Y. Acad. Sci. 1066, 92–105 (2005).

    Article  Google Scholar 

  94. Bangham, A. D. & Horne, R. W. Action of saponin on biological cell membranes. Nature 196, 952–953 (1962).

    Article  Google Scholar 

  95. Patel, G. K. et al. Comparative analysis of exosome isolation methods using culture supernatant for optimum yield, purity and downstream applications. Sci. Rep. 9, 5335 (2019).

    Article  Google Scholar 

  96. Linares, R., Tan, S., Gounou, C., Arraud, N. & Brisson, A. R. High-speed centrifugation induces aggregation of extracellular vesicles. J. Extracell. Vesicle 4, 29509 (2015).

    Article  Google Scholar 

  97. Li, Z. et al. In vitro and in vivo RNA inhibition by CD9-HuR functionalized exosomes encapsulated with miRNA or CRISPR/dCas9. Nano Lett. 19, 19–28 (2019).

    Article  Google Scholar 

  98. Gee, P. et al. Extracellular nanovesicles for packaging of CRISPR-Cas9 protein and sgRNA to induce therapeutic exon skipping. Nat. Commun. 11, 1334 (2020).

    Article  Google Scholar 

  99. Chitti, S. V. et al. Vesiclepedia 2024: an extracellular vesicles and extracellular particles repository. Nucleic Acids Res. 52, D1694–D1698 (2023).

    Article  Google Scholar 

  100. Keerthikumar, S. et al. ExoCarta: a web-based compendium of exosomal cargo. J. Mol. Biol. 428, 688–692 (2016).

    Article  Google Scholar 

  101. Cvjetkovic, A., Lötvall, J. & Lässer, C. The influence of rotor type and centrifugation time on the yield and purity of extracellular vesicles. J. Extracell. Vesicles 3, 23111 (2014).

    Article  Google Scholar 

  102. Chou, C.-Y. et al. Improving the purity of extracellular vesicles by removal of lipoproteins from size exclusion chromatography- and ultracentrifugation-processed samples. ACS Appl. Mater. Interfaces 16, 44386–44398 (2024).

    Article  Google Scholar 

  103. Xabier, O. et al. Differential detergent sensitivity of extracellular vesicle subpopulations. Org. Biomol. Chem. 13, 9775–9782 (2015).

    Article  Google Scholar 

  104. Koudelka, Š & Turánek, J. Liposomal paclitaxel formulations. J. Control. Release 163, 322–334 (2012).

    Article  Google Scholar 

  105. Alskär, L. C., Porter, C. J. H. & Bergström, C. A. S. Tools for early prediction of drug loading in lipid-based formulations. Mol. Pharm. 13, 251–261 (2016).

    Article  Google Scholar 

  106. Tang, T.-T. et al. Extracellular vesicle-encapsulated IL-10 as novel nanotherapeutics against ischemic AKI. Sci. Adv. 6, eaaz0748 (2020).

    Article  Google Scholar 

  107. Kirwin, K. et al. 572 Combination therapy of exoSTING, exoIL-12 activates systemic anti-tumor immunity. J. Immunother. Cancer 9, A601 (2021).

    Google Scholar 

  108. Abusamra, A. J. et al. Tumor exosomes expressing Fas ligand mediate CD8+ T-cell apoptosis. Blood Cells Mol. Dis. 35, 169–173 (2005).

    Article  Google Scholar 

  109. Budayr, O. M., Miller, B. C. & Nguyen, J. Harnessing extracellular vesicle-mediated crosstalk between T cells and cancer cells for therapeutic applications. J. Control. Release 378, 266–280 (2025).

    Article  Google Scholar 

  110. Sakla, M., Breitinger, U., Breitinger, H.-G., Mansour, S. & Tammam, S. N. Delivery of trans-membrane proteins by liposomes; the effect of liposome size and formulation technique on the efficiency of protein delivery. Int. J. Pharm. 606, 120879 (2021).

    Article  Google Scholar 

  111. Wang, Z. et al. Inhalation of ACE2-expressing lung exosomes provides prophylactic protection against SARS-CoV-2. Nat. Commun. 15, 2236 (2024).

    Article  Google Scholar 

  112. Rawlings, A. E. Membrane proteins: always an insoluble problem? Biochem. Soc. Trans. 44, 790–795 (2016).

    Article  Google Scholar 

  113. Beit-Yannai, E., Tabak, S. & Stamer, W. D. Physical exosome:exosome interactions. J. Cell Mol. Med. 22, 2001–2006 (2018).

    Article  Google Scholar 

  114. Alvarez-Erviti, L. et al. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat. Biotechnol. 29, 341–345 (2011).

    Article  Google Scholar 

  115. Kooijmans, S. A. A. et al. Electroporation-induced siRNA precipitation obscures the efficiency of siRNA loading into extracellular vesicles. J. Control. Release 172, 229–238 (2013).

    Article  Google Scholar 

  116. Abreu, R. C. D. et al. Exogenous loading of miRNAs into small extracellular vesicles. J. Extracell. Vesicles 10, e12111 (2021).

    Article  Google Scholar 

  117. Maugeri, M. et al. Linkage between endosomal escape of LNP-mRNA and loading into EVs for transport to other cells. Nat. Commun. 10, 4333 (2019).

    Article  Google Scholar 

  118. Lamichhane, T. N., Raiker, R. S. & Jay, S. M. Exogenous DNA loading into extracellular vesicles via electroporation is size-dependent and enables limited gene delivery. Mol. Pharm. 12, 3650–3657 (2015).

    Article  Google Scholar 

  119. Bonacquisti, E. E. et al. Fluorogenic RNA-based biomaterials for imaging and tracking the cargo of extracellular vesicles. J. Control. Release 374, 349–368 (2024).

    Article  Google Scholar 

  120. Chen, C. et al. Active cargo loading into extracellular vesicles: highlights the heterogeneous encapsulation behaviour. J. Extracell. Vesicles 10, e12163 (2021).

    Article  Google Scholar 

  121. Willms, E. et al. Cells release subpopulations of exosomes with distinct molecular and biological properties. Sci. Rep. 6, 22519 (2016).

    Article  Google Scholar 

  122. Liao, S. et al. Transfection potency of lipid nanoparticles containing mRNA depends on relative loading levels. ACS Appl. Mater. Interfaces 17, 3097–3105 (2024).

    Article  Google Scholar 

  123. Center for Drug Evaluation and Research Center for Biologics Evaluation and Research. Guidance for Industry Exposure-Response Relationships — Study Design, Data Analysis, and Regulatory Applications (FDA, 2003).

  124. Qiao, L. et al. Tumor cell-derived exosomes home to their cells of origin and can be used as Trojan horses to deliver cancer drugs. Theranostics 10, 3474–3487 (2020).

    Article  Google Scholar 

  125. Jurgielewicz, B. J. et al. Kinetics and specificity of HEK293T extracellular vesicle uptake using imaging flow cytometry. Nanoscale Res. Lett. 15, 170 (2020).

    Article  Google Scholar 

  126. Sancho-Albero, M. et al. Exosome origin determines cell targeting and the transfer of therapeutic nanoparticles towards target cells. J. Nanobiotechnol. 17, 16 (2019).

    Article  Google Scholar 

  127. Rana, S., Yue, S., Stadel, D. & Zöller, M. Toward tailored exosomes: the exosomal tetraspanin web contributes to target cell selection. Int. J. Biochem. Cell Biol. 44, 1574–1584 (2012).

    Article  Google Scholar 

  128. Hoshino, A. et al. Tumour exosome integrins determine organotropic metastasis. Nature 527, 7578 (2015).

    Article  Google Scholar 

  129. Takov, K., Yellon, D. M. & Davidson, S. M. Confounding factors in vesicle uptake studies using fluorescent lipophilic membrane dyes. J. Extracell. Vesicles 6, 1388731 (2017).

    Article  Google Scholar 

  130. Pužar Dominkuš, P. et al. PKH26 labeling of extracellular vesicles: characterization and cellular internalization of contaminating PKH26 nanoparticles. Biochim. Biophys. Acta Biomembr. 1860, 1350–1361 (2018).

    Article  Google Scholar 

  131. Dehghani, M., Gulvin, S. M., Flax, J. & Gaborski, T. R. Systematic evaluation of PKH labelling on extracellular vesicle size by nanoparticle tracking analysis. Sci. Rep. 10, 9533 (2020).

    Article  Google Scholar 

  132. Simonsen, J. B. Pitfalls associated with lipophilic fluorophore staining of extracellular vesicles for uptake studies. J. Extracell. Vesicles 8, 1582237 (2019).

    Article  Google Scholar 

  133. Lau, S. Y., Kang, M., Hisey, C. L. & Chamley, L. W. Studying exogenous extracellular vesicle biodistribution by in vivo fluorescence microscopy. Dis. Model. Mech. 16, dmm050074 (2023).

    Article  Google Scholar 

  134. Lai, C. P. et al. Visualization and tracking of tumour extracellular vesicle delivery and RNA translation using multiplexed reporters. Nat. Commun. 6, 7029 (2015).

    Article  Google Scholar 

  135. Gupta, D. et al. Quantification of extracellular vesicles in vitro and in vivo using sensitive bioluminescence imaging. J. Extracell. Vesicles 9, 1800222 (2020).

    Article  Google Scholar 

  136. Fordjour, F. K., Guo, C., Ai, Y., Daaboul, G. G. & Gould, S. J. A shared, stochastic pathway mediates exosome protein budding along plasma and endosome membranes. J. Biol. Chem. 298, 102394 (2022).

    Article  Google Scholar 

  137. Mathieu, M. et al. Specificities of exosome versus small ectosome secretion revealed by live intracellular tracking of CD63 and CD9. Nat. Commun. 12, 4389 (2021).

    Article  Google Scholar 

  138. Lu, C.-H. et al. Preclinical characterization and in vivo imaging of 111In-labeled mesenchymal stem cell-derived extracellular vesicles. Mol. Imaging Biol. 23, 361–371 (2020).

    Article  Google Scholar 

  139. Royo, F. et al. Modification of the glycosylation of extracellular vesicles alters their biodistribution in mice. Nanoscale 11, 1531–1537 (2019).

    Article  Google Scholar 

  140. Lázaro-Ibáñez, E. et al. Selection of fluorescent, bioluminescent, and radioactive tracers to accurately reflect extracellular vesicle biodistribution in vivo. ACS Nano 15, 3212–3227 (2021).

    Article  Google Scholar 

  141. Hwang, D. W. et al. Chemical modulation of bioengineered exosomes for tissue-specific biodistribution. Adv. Therapeutics 2, 1900111 (2019).

    Article  Google Scholar 

  142. Gallo, A., Tandon, M., Alevizos, I. & Illei, G. G. The majority of microRNAs detectable in serum and saliva is concentrated in exosomes. PLoS One 7, e30679 (2012).

    Article  Google Scholar 

  143. Mori, M. A., Ludwig, R. G., Garcia-Martin, R., Brandão, B. B. & Kahn, C. R. Extracellular miRNAs: from biomarkers to mediators of physiology and disease. Cell Metab. 30, 656–673 (2019).

    Article  Google Scholar 

  144. Bi, Y. et al. Exosomal miR-302b rejuvenates aging mice by reversing the proliferative arrest of senescent cells. Cell Metab. 37, 527–541.e6 (2025).

    Article  Google Scholar 

  145. Wiklander, O. P. B. et al. Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting. J. Extracell. Vesicles 4, 26316 (2015).

    Article  Google Scholar 

  146. Welsh, J. A. et al. Minimal information for studies of extracellular vesicles (MISEV2023): from basic to advanced approaches. J. Extracell. Vesicles 13, e12404 (2024).

    Article  Google Scholar 

  147. Wortzel, I., Dror, S., Kenific, C. M. & Lyden, D. Exosome-mediated metastasis: communication from a distance. Dev. Cell 49, 347–360 (2019).

    Article  Google Scholar 

  148. Raith, M. et al. Obesity and inflammation influence pharmacokinetic profiles of PEG-based nanoparticles. J. Control. Release 355, 434–445 (2023).

    Article  Google Scholar 

  149. Manca, S. et al. Milk exosomes are bioavailable and distinct microRNA cargos have unique tissue distribution patterns. Sci. Rep. 8, 11321 (2018).

    Article  Google Scholar 

  150. Khare, H. A., Bazban-Shotorbani, S., Binderup, T., Kjaer, A. & Kamaly, N. Effect of size and targeting agent on biodistribution of polystyrene nanoparticles in apolipoprotein E knock-out and wild-type mice. Diagnostics 15, 2140 (2025).

    Article  Google Scholar 

  151. Zhang, P. et al. In vivo tracking of multiple tumor exosomes labeled by phospholipid-based bioorthogonal conjugation. Anal. Chem. 90, 11273–11279 (2018).

    Article  Google Scholar 

  152. Graham Jr, R. C. & Karnovsky, M. J. Glomerular permeability. Ultrastructural cytochemical studies using peroxidases as protein tracers. J. Exp. Med. 124, 1123–1134 (1966).

    Google Scholar 

  153. Banks, W. A. et al. Transport of extracellular vesicles across the blood-brain barrier: brain pharmacokinetics and effects of inflammation. Int. J. Mol. Sci. 21, 4407 (2020).

    Article  Google Scholar 

  154. Wu, J. The enhanced permeability and retention (EPR) effect: the significance of the concept and methods to enhance its application. J. Pers. Med. 11, 771 (2021).

    Article  Google Scholar 

  155. Peng, Z. et al. Tumor-derived extracellular vesicles enable tumor tropism chemo-genetherapy for local immune activation in triple-negative breast cancer. ACS Nano 18, 30943–30956 (2024).

    Article  Google Scholar 

  156. Samal, S., Panda, G. P., Shyamal, S., Das, K. & Dash, M. Surface engineered osteoblast-extracellular vesicles serve as an efficient carrier for drug and small RNA to actively target osteosarcoma. ACS Biomater. Sci. Eng. 10, 7466–7481 (2024).

    Article  Google Scholar 

  157. Kooijmans, S. A. A. et al. PEGylated and targeted extracellular vesicles display enhanced cell specificity and circulation time. J. Control. Release 224, 77–85 (2016).

    Article  Google Scholar 

  158. Du, J. et al. Designer exosomes for targeted and efficient ferroptosis induction in cancer via chemo-photodynamic therapy. Theranostics 11, 8185–8196 (2021).

    Article  Google Scholar 

  159. Alharbi, M. et al. Enhancing precision targeting of ovarian cancer tumor cells in vivo through extracellular vesicle engineering. Int. J. Cancer 155, 1510–1523 (2024).

    Article  Google Scholar 

  160. Manjiao, Z. et al. SPION decorated exosome delivery of TNF-α to cancer cell membranes through magnetism. Nanoscale 12, 173–188 (2019).

    Google Scholar 

  161. Heidarzadeh, M., Zarebkohan, A., Rahbarghazi, R. & Sokullu, E. Protein corona and exosomes: new challenges and prospects. Cell Commun. Signal. 21, 64 (2023).

    Article  Google Scholar 

  162. Willms, E., Cabañas, C., Mäger, I., Wood, M. J. A. & Vader, P. Extracellular vesicle heterogeneity: subpopulations, isolation techniques, and diverse functions in cancer progression. Front. Immunol. 9, 738 (2018).

    Article  Google Scholar 

  163. Verderio, C., Gabrielli, M. & Giussani, P. Role of sphingolipids in the biogenesis and biological activity of extracellular vesicles. J. Lipid Res. 59, 1325–1340 (2018).

    Article  Google Scholar 

  164. Liu, P., Chen, G. & Zhang, J. A review of liposomes as a drug delivery system: current status of approved products, regulatory environments, and future perspectives. Molecules 27, 1372 (2022).

    Article  Google Scholar 

  165. Jung, H. N., Lee, S.-Y., Lee, S., Youn, H. & Im, H.-J. Lipid nanoparticles for delivery of RNA therapeutics: current status and the role of in vivo imaging. Theranostics 12, 7509–7531 (2022).

    Article  Google Scholar 

  166. Leung, A. K. K. et al. Lipid nanoparticles containing siRNA synthesized by microfluidic mixing exhibit an electron-dense nanostructured core. J. Phys. Chem. C Nanomater. Interfaces 116, 18440–18450 (2012).

    Article  Google Scholar 

  167. Fuhrmann, G., Serio, A., Mazo, M., Nair, R. & Stevens, M. M. Active loading into extracellular vesicles significantly improves the cellular uptake and photodynamic effect of porphyrins. J. Control. Release 205, 35–44 (2015).

    Article  Google Scholar 

  168. Kang, M. et al. Placental extracellular vesicles can be loaded with plasmid DNA. Mol. Pharm. 20, 1898–1913 (2023).

    Article  Google Scholar 

  169. Azizah, A. et al. In vivo delivery of plasmid DNA by lipid nanoparticles: the influence of ionizable cationic lipids on organ-selective gene expression. Biomater. Sci. 10, 2940–2952 (2022).

    Article  Google Scholar 

  170. Li, T. et al. CRISPR/Cas9 therapeutics: progress and prospects. Signal. Transduct. Target. Ther. 8, 36 (2023).

    Article  Google Scholar 

  171. Wu, F. et al. Lipid nanoparticles for delivery of CRISPR gene editing components. Small Methods 10, e2401632 (2025).

    Article  Google Scholar 

  172. Kim, S. M. et al. Cancer-derived exosomes as a delivery platform of CRISPR/Cas9 confer cancer cell tropism-dependent targeting. J. Control. Release 266, 8–16 (2017).

    Article  Google Scholar 

  173. Liu, X. et al. Engineered extracellular vesicle-delivered CRISPR/Cas9 for radiotherapy sensitization of glioblastoma. ACS Nano 17, 16432–16447 (2023).

    Article  Google Scholar 

  174. Berggreen, A. H., Petersen, J. L., Lin, L., Benabdellah, K. & Luo, Y. CRISPR delivery with extracellular vesicles: promises and challenges. J. Extracell. Biol. 2, e111 (2023).

    Article  Google Scholar 

  175. Chen, R. et al. Friend or foe? evidence indicates endogenous exosomes can deliver functional gRNA and cas9 protein. Small 15, 1902686 (2019).

    Article  Google Scholar 

  176. Kazemian, P. et al. Lipid-nanoparticle-based delivery of CRISPR/Cas9 genome-editing components. Mol. Pharm. 19, 1669–1686 (2022).

    Article  Google Scholar 

  177. Ndeupen, S. et al. The mRNA-LNP platform’s lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory. iScience 24, 103479 (2021).

    Article  Google Scholar 

  178. Tahtinen, S. et al. IL-1 and IL-1ra are key regulators of the inflammatory response to RNA vaccines. Nat. Immunol. 23, 532–542 (2022).

    Article  Google Scholar 

  179. Somiya, M., Yoshioka, Y. & Ochiya, T. Biocompatibility of highly purified bovine milk-derived extracellular vesicles. J. Extracell. Vesicles 7, 1440132 (2018).

    Article  Google Scholar 

  180. Chew, W. L. Immunity to CRISPR Cas9 and Cas12a therapeutics. Wiley Interdiscip. Rev. Syst. Biol. Med. 10, e1408 (2018).

    Article  Google Scholar 

  181. Wang, D. et al. Adenovirus-mediated somatic genome editing of pten by CRISPR/Cas9 in mouse liver in spite of cas9-specific immune responses. Hum. Gene Ther. 26, 432–442 (2015).

    Article  Google Scholar 

  182. Kim, S. et al. CRISPR RNAs trigger innate immune responses in human cells. Genome Res. 28, 367–373 (2018).

    Article  Google Scholar 

  183. Driedonks, T. et al. Pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to Macaca nemestrina. J. Extracell. Biol. 1, e59 (2022).

    Article  Google Scholar 

  184. Johnsen, K. B. et al. On the use of liposome controls in studies investigating the clinical potential of extracellular vesicle-based drug delivery systems — a commentary. J. Control. Release 269, 10–14 (2018).

    Article  Google Scholar 

  185. Chen, K. et al. Lung and liver editing by lipid nanoparticle delivery of a stable CRISPR–Cas9 ribonucleoprotein. Nat. Biotechnol. 43, 1445–1457 (2025).

    Article  Google Scholar 

  186. Jiang, C. et al. A non-viral CRISPR/Cas9 delivery system for therapeutically targeting HBV DNA and pcsk9 in vivo. Cell Res. 27, 440–443 (2017).

    Article  Google Scholar 

  187. Finn, J. D. et al. A single administration of CRISPR/Cas9 lipid nanoparticles achieves robust and persistent in vivo genome editing. Cell Rep. 22, 2227–2235 (2018).

    Article  Google Scholar 

  188. Wan, T. et al. Exosome-mediated delivery of Cas9 ribonucleoprotein complexes for tissue-specific gene therapy of liver diseases. Sci. Adv. 8, eabp9435 (2022).

    Article  Google Scholar 

  189. Majeau, N. et al. Serum extracellular vesicles for delivery of CRISPR-CAS9 ribonucleoproteins to modify the dystrophin gene. Mol. Ther. 30, 2429–2442 (2022).

    Article  Google Scholar 

  190. Yao, X. et al. Engineered extracellular vesicles as versatile ribonucleoprotein delivery vehicles for efficient and safe CRISPR genome editing. J. Extracell. Vesicles 10, e12076 (2021).

    Article  Google Scholar 

  191. Smyth, T. J., Redzic, J. S., Graner, M. W. & Anchordoquy, T. J. Examination of the specificity of tumor cell derived exosomes with tumor cells in vitro. Biochim. Biophys. Acta 1838, 2954–2965 (2014).

    Article  Google Scholar 

  192. Bonsergent, E. et al. Quantitative characterization of extracellular vesicle uptake and content delivery within mammalian cells. Nat. Commun. 12, 1864 (2021).

    Article  Google Scholar 

  193. Sahay, G. et al. Efficiency of siRNA delivery by lipid nanoparticles is limited by endocytic recycling. Nat. Biotechnol. 31, 653–658 (2013).

    Article  Google Scholar 

  194. Gilleron, J. et al. Image-based analysis of lipid nanoparticle-mediated siRNA delivery, intracellular trafficking and endosomal escape. Nat. Biotechnol. 31, 638–646 (2013).

    Article  Google Scholar 

  195. Chatterjee, S. et al. Endosomal escape: a bottleneck for LNP-mediated therapeutics. Proc. Natl Acad. Sci. USA 121, e2307800120 (2024).

    Article  Google Scholar 

  196. Bernhard, N. et al. Nanoparticles as transfection agents: a comprehensive study with ten different cell lines. RSC Adv. 6, 18102–18112 (2016).

    Article  Google Scholar 

  197. Reshke, R. et al. Reduction of the therapeutic dose of silencing RNA by packaging it in extracellular vesicles via a pre-microRNA backbone. Nat. Biomed. Eng. 4, 52–68 (2020).

    Article  Google Scholar 

  198. Saber, N., Senti, M. E. & Schiffelers, R. M. Lipid nanoparticles for nucleic acid delivery beyond the liver. Hum. Gene Ther. 35, 617–627 (2024).

    Article  Google Scholar 

  199. Suk, J. S., Xu, Q., Kim, N., Hanes, J. & Ensign, L. M. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv. Drug Deliv. Rev. 99, 28–51 (2015).

    Article  Google Scholar 

  200. Lai, C. P. et al. Dynamic biodistribution of extracellular vesicles in vivo using a multimodal imaging reporter. ACS Nano 8, 483–494 (2014).

    Article  Google Scholar 

  201. Lee, C. S., Kulkarni, Y., Pierre, V., Maski, M. & Wanner, C. Adverse impacts of PEGylated protein therapeutics: a targeted literature review. BioDrugs 38, 795–819 (2024).

    Article  Google Scholar 

  202. Simon, L. et al. Surface modification of extracellular vesicles with polyoxazolines to enhance their plasma stability and tumor accumulation. Biomaterials 313, 122748 (2025).

    Article  Google Scholar 

  203. Cheng, Q. et al. Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR–Cas gene editing. Nat. Nanotechnol. 15, 313–320 (2020).

    Article  Google Scholar 

  204. Hosseini-Kharat, M., Bremmell, K. E. & Prestidge, C. A. Why do lipid nanoparticles target the liver? Understanding of biodistribution and liver-specific tropism. Mol. Ther. Methods Clin. Dev. 33, 101436 (2025).

    Article  Google Scholar 

  205. Ochoa-Sánchez, C., Rodríguez-León, E., Iñiguez-Palomares, R. & Rodríguez-Beas, C. Brief comparison of the efficacy of cationic and anionic liposomes as nonviral delivery systems. ACS Omega 9, 46664–46678 (2024).

    Article  Google Scholar 

  206. Cui, S. et al. Correlation of the cytotoxic effects of cationic lipids with their headgroups. Toxicol. Res. 7, 473–479 (2018).

    Article  Google Scholar 

  207. Lv, H., Zhang, S., Wang, B., Cui, S. & Yan, J. Toxicity of cationic lipids and cationic polymers in gene delivery. J. Control. Release 114, 100–109 (2006).

    Article  Google Scholar 

  208. Lee, Y. et al. Immunogenicity of lipid nanoparticles and its impact on the efficacy of mRNA vaccines and therapeutics. Exp. Mol. Med. 55, 2085–2096 (2023).

    Article  Google Scholar 

  209. Dong, X. et al. Intrapleural infusion of tumor cell-derived microparticles packaging methotrexate or saline combined with pemetrexed-cisplatin chemotherapy for the treatment of malignant pleural effusion in advanced non-squamous non-small cell lung cancer: a double-blind, randomized, placebo-controlled study. Front. Immunol. 13, 1002938 (2022).

    Article  Google Scholar 

  210. Driedonks, T. A. P., Jiang, L., Gololobova, O., Liao, Z. & Witwer, K. W. ELISA-based detection of immunoglobulins against extracellular vesicles in blood plasma. J. Extracell. Biol. 3, e129 (2024).

    Article  Google Scholar 

  211. Cullis, P. R., Felgner, P. L., Cullis, P. R. & Felgner, P. L. The 60-year evolution of lipid nanoparticles for nucleic acid delivery. Nat. Rev. Drug Discov. 23, 709–722 (2024).

    Article  Google Scholar 

  212. Pattni, B. S., Chupin, V. V. & Torchilin, V. P. New developments in liposomal drug delivery. Chem. Rev. 115, 10938–10966 (2015).

    Article  Google Scholar 

  213. Davies, B. & Morris, T. Physiological parameters in laboratory animals and humans. Pharm. Res. 10, 1093–1095 (1993).

    Article  Google Scholar 

  214. Gudbergsson, J. M. et al. Systematic review of factors influencing extracellular vesicle yield from cell cultures. Cytotechnology 68, 579–592 (2015).

    Article  Google Scholar 

  215. Baker, M. & Baker, M. Reproducibility: respect your cells!. Nature 537, 7620 (2016).

    Article  Google Scholar 

  216. Nguyen, V. V. T., Witwer, K. W., Verhaar, M. C., Strunk, D. & Balkom, B. W. M. V. Functional assays to assess the therapeutic potential of extracellular vesicles. J. Extracell. Vesicles 10, e12033 (2020).

    Article  Google Scholar 

  217. Xu, S. et al. Comparison of nanoimaging and nanoflow based detection of extracellular vesicles at a single particle resolution. J. Extracell. Biol. 3, e70016 (2024).

    Article  Google Scholar 

  218. Kobayashi, H. et al. Precise analysis of single small extracellular vesicles using flow cytometry. Sci. Rep. 14, 7465 (2024).

    Article  Google Scholar 

  219. Woud, W. W. et al. An imaging flow cytometry-based methodology for the analysis of single extracellular vesicles in unprocessed human plasma. Commun. Biol. 5, 633 (2022).

    Article  Google Scholar 

  220. Morales-Kastresana, A. et al. High-fidelity detection and sorting of nanoscale vesicles in viral disease and cancer. J. Extracell. Vesicles 8, 1597603 (2019).

    Article  Google Scholar 

  221. Welsh, J. A. et al. MIFlowCyt-EV: a framework for standardized reporting of extracellular vesicle flow cytometry experiments. J. Extracell. Vesicles 9, 1713526 (2020).

    Article  Google Scholar 

  222. Zhang, J. et al. Immunomagnetic sequential ultrafiltration (iSUF) platform for enrichment and purification of extracellular vesicles from biofluids. Sci. Rep. 11, 8034 (2021).

    Article  Google Scholar 

  223. Nizamudeen, Z. et al. Rapid and accurate analysis of stem cell-derived extracellular vesicles with super resolution microscopy and live imaging. Biochim. Biophys. Acta Mol. Cell Res. 1865, 1891–1900 (2018).

    Article  Google Scholar 

  224. Jensen, E. & Crossman, D. J. Technical review: types of imaging — direct STORM. Anat. Rec. 297, 2227–2231 (2014).

    Article  Google Scholar 

  225. McNamara, R. P. et al. Imaging of surface microdomains on individual extracellular vesicles in 3-D. J. Extracell. Vesicles 11, e12191 (2022).

    Article  Google Scholar 

  226. Théry, C. et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J. Extracell. Vesicles 7, 1535750 (2018).

    Article  Google Scholar 

Download references