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Extracellular vesicles as a next-generation drug delivery platform

Herrmann, Inge Katrin, Wood, Matthew John Andrew, Fuhrmann, Gregor·2021·Nature Nanotechnology
DOI 10.1038/s41565-021-00931-2
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  1. van der Meel, R. et al. Smart cancer nanomedicine. Nat. Nanotechnol. 14, 1007–1017 (2019). · DOI
  2. Elsharkasy, O. M. et al. Extracellular vesicles as drug delivery systems: why and how? Adv. Drug Deliv. Rev. 159, 332–343 (2020). · DOI
  3. Möller, A. & Lobb, R. J. The evolving translational potential of small extracellular vesicles in cancer. Nat. Rev. Cancer 20, 697–709 (2020). · DOI
  4. El Andaloussi, S., Mager, I., Breakefield, X. O. & Wood, M. J. A. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat. Rev. Drug Discov. 12, 347–357 (2013). · DOI · Paper page
  5. Mathieu, M., Martin-Jaular, L., Lavieu, G. & Théry, C. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat. Cell Biol. 21, 9–17 (2019). · DOI
  6. Hoppstädter, J. et al. Toll-like receptor 2 release by macrophages: an anti-inflammatory program induced by glucocorticoids and lipopolysaccharide. Front. Immunol. 10, 1634 (2019). This original work presented one of the first examples of modifying EVs with polyethylene glycol and the influence on in vivo biodistribution of vesicles. · DOI
  7. 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). · DOI
  8. Woith, E., Fuhrmann, G. & Melzig, M. F. Extracellular vesicles—connecting kingdoms. Int. J. Mol. Sci. 20, 5695 (2019). · DOI
  9. Witwer, K. W. & Théry, C. Extracellular vesicles or exosomes? On primacy, precision, and popularity influencing a choice of nomenclature. J. Extracell. Vesicles 8, 1648167–1648167 (2019). · DOI
  10. Cabeza, L. et al. Cancer therapy based on extracellular vesicles as drug delivery vehicles. J. Control. Release 327, 296–315 (2020). · DOI
  11. Tkach, M., Kowal, J. & Théry, C. Why the need and how to approach the functional diversity of extracellular vesicles. Phil. Trans. R. Soc. B 373, 20160479 (2018). · DOI
  12. Hurwitz, S. N. et al. Proteomic profiling of NCI-60 extracellular vesicles uncovers common protein cargo and cancer type-specific biomarkers. Oncotarget 7, 86999–87015 (2016). · DOI
  13. Rocha, S. et al. 3D cellular architecture affects microRNA and protein cargo of extracellular vesicles. Adv. Sci. 6, 1800948 (2019). · DOI
  14. Fuhrmann, G., Herrmann, I. & Stevens, M. M. Cell-derived vesicles for drug therapy and diagnostics: opportunities and challenges. Nano Today 10, 397–409 (2015). · DOI
  15. Gross, J. C., Chaudhary, V., Bartscherer, K. & Boutros, M. Active Wnt proteins are secreted on exosomes. Nat. Cell Biol. 14, 1036–1045 (2012). · DOI
  16. Smith, S. A., Selby, L. I., Johnston, A. P. R. & Such, G. K. The endosomal escape of nanoparticles: toward more efficient cellular delivery. Bioconjugate Chem. 30, 263–272 (2019). · DOI
  17. van den Boorn, J. G., Schlee, M., Coch, C. & Hartmann, G. SiRNA delivery with exosome nanoparticles. Nat. Biotechnol. 29, 325–326 (2011). · DOI · Paper page
  18. 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). · DOI
  19. Xu, R. et al. Extracellular vesicles in cancer—implications for future improvements in cancer care. Nat. Rev. Clin. Oncol. 15, 617–638 (2018). · DOI
  20. Keklikoglou, I. et al. Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models. Nat. Cell Biol. 21, 190–202 (2019). · DOI
  21. Nolte-‘t Hoen, E., Cremer, T., Gallo, R. C. & Margolis, L. B. Extracellular vesicles and viruses: are they close relatives? Proc. Natl Acad. Sci. USA 113, 9155–9161 (2016). · DOI
  22. Toyofuku, M., Nomura, N. & Eberl, L. Types and origins of bacterial membrane vesicles. Nat. Rev. Microbiol. 17, 13–24 (2019). · DOI
  23. Mehanny, M., Koch, M., Lehr, C.-M. & Fuhrmann, G. Streptococcal extracellular membrane vesicles are rapidly internalized by immune cells and alter their cytokine release. Front. Immunol. 11, 80 (2020). · DOI
  24. Goes, A. et al. Myxobacteria-derived outer membrane vesicles: potential applicability against intracellular infections. Cells 9, 194 (2020). · DOI
  25. Gujrati, V. et al. Bioengineered bacterial outer membrane vesicles as cell-specific drug-delivery vehicles for cancer therapy. ACS Nano 8, 1525–1537 (2014). · DOI
  26. Kuhn, T., Koch, M. & Fuhrmann, G. Probiomimetics—novel lactobacillus-mimicking microparticles show anti-inflammatory and barrier-protecting effects in gastrointestinal models. Small 16, 2003158 (2020). · DOI
  27. Murali, V. P. & Holmes, C. A. Biomaterial-based extracellular vesicle delivery for therapeutic applications. Acta Biomater. 124, 88–107 (2021). · DOI
  28. Pourtalebi Jahromi, L. & Fuhrmann, G. Bacterial extracellular vesicles: understanding biology promotes applications as nanopharmaceuticals. Adv. Drug Deliv. Rev. 173, 125–140 (2021). · DOI
  29. Ayers, L., Pink, R., Carter, D. R. F. & Nieuwland, R. Clinical requirements for extracellular vesicle assays. J. Extracell. Vesicles 8, 1593755 (2019). · DOI
  30. Nassar, W. et al. Umbilical cord mesenchymal stem cells derived extracellular vesicles can safely ameliorate the progression of chronic kidney diseases. Biomater. Res. 20, 21 (2016). · DOI
  31. Wang, J., Bonacquisti, E. E., Brown, A. D. & Nguyen, J. Boosting the biogenesis and secretion of mesenchymal stem cell-derived exosomes. Cells 9, 660 (2020). · DOI
  32. Kou, X. et al. The Fas/Fap-1/Cav-1 complex regulates IL-1RA secretion in mesenchymal stem cells to accelerate wound healing. Sci. Transl. Med. 10, eaai8524 (2018). · DOI
  33. Lener, T. et al. Applying extracellular vesicles based therapeutics in clinical trials—an ISEV position paper. J. Extracell. Vesicles 4, 30087 (2015). A seminal position paper from an international consortium of EV scientists on the regulatory needs when studying vesicles in clinical trials. · DOI · Paper page
  34. Börger, V. et al. International Society for Extracellular Vesicles and International Society for Cell and Gene Therapy statement on extracellular vesicles from mesenchymal stromal cells and other cells: considerations for potential therapeutic agents to suppress coronavirus disease-19. Cytotherapy 22, 482–485 (2020). · DOI
  35. Galipeau, J. The mesenchymal stromal cells dilemma—does a negative phase III trial of random donor mesenchymal stromal cells in steroid-resistant graft-versus-host disease represent a death knell or a bump in the road? Cytotherapy 15, 2–8 (2013). · DOI
  36. Witwer, K. W. et al. Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications. J. Extracell. Vesicles 8, 1609206 (2019). · DOI
  37. Rohde, E., Pachler, K. & Gimona, M. Manufacturing and characterization of extracellular vesicles from umbilical cord-derived mesenchymal stromal cells for clinical testing. Cytotherapy 21, 581–592 (2019). This perspective provides a roadmap for the development of EV-based therapeutics in a very early stage of manufacturing as well as during early clinical safety and proof-of-concept testing. · DOI · Paper page
  38. Zipkin, M. Exosome redux. Nat. Biotechnol. 37, 1395–1400 (2019). · DOI
  39. Chuo, S. T.-Y., Chien, J. C.-Y. & Lai, C. P.-K. Imaging extracellular vesicles: current and emerging methods. J. Biomed. Sci. 25, 91 (2018). · DOI
  40. Zeev-Ben-Mordehai, T., Vasishtan, D., Siebert, C. A., Whittle, C. & Grünewald, K. Extracellular vesicles: a platform for the structure determination of membrane proteins by cryo-EM. Structure 22, 1687–1692 (2014). · DOI
  41. Kreimer, S. et al. Mass-spectrometry-based molecular characterization of extracellular vesicles: lipidomics and proteomics. J. Proteome Res 14, 2367–2384 (2015). · DOI
  42. Welsh, J. A. et al. Towards defining reference materials for measuring extracellular vesicle refractive index, epitope abundance, size and concentration. J. Extracell. Vesicles 9, 1816641 (2020). This paper provides guidelines on the standardization of commonly used analysis platforms for characterizing EV refractive index, epitope abundance, size and concentration. · DOI
  43. Alvarez-Erviti, L. et al. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat. Biotechnol. 29, 341–345 (2011). · DOI · Paper page
  44. Mittelbrunn, M. et al. Unidirectional transfer of micro RNA-loaded exosomes from T cells to antigen-presenting cells. Nat. Commun. 2, 282 (2011). · DOI
  45. 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). · DOI
  46. 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). · DOI · Paper page
  47. Dai, J. et al. Exosomes: key players in cancer and potential therapeutic strategy. Signal Transduct. Target. Ther. 5, 145 (2020). · DOI · Paper page
  48. Lai, C. P. et al. Dynamic biodistribution of extracellular vesicles in vivo using a multimodal imaging reporter. ACS Nano 8, 483–494 (2014). · DOI
  49. Henriksen, J. R. et al. Remote loading of 64Cu2+ into liposomes without the use of ion transport enhancers. ACS Appl. Mater. Interfaces 7, 22796–22806 (2015). · DOI
  50. 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). · DOI
  51. Lenzini, S., Bargi, R., Chung, G. & Shin, J.-W. Matrix mechanics and water permeation regulate extracellular vesicle transport. Nat. Nanotechnol. 15, 217–223 (2020). In this recent work, the influence of mechanical properties of EVs on the diffusion from extracellular-matrix-simulating environments was evaluated. · DOI
  52. Geigert, J. in The Challenge of CMC Regulatory Compliance for Biopharmaceuticals and Other Biologics (ed. Geigert, J.) 221–237 (Springer, 2013). · DOI
  53. Somiya, M., Yoshioka, Y. & Ochiya, T. Biocompatibility of highly purified bovine milk-derived extracellular vesicles. J. Extracell. Vesicles 7, 1440132 (2018). · DOI
  54. McVey, M. J. et al. Platelet extracellular vesicles mediate transfusion-related acute lung injury by imbalancing the sphingolipid rheostat. Blood 137, 690–701 (2021). · DOI
  55. Balachandran, B. & Yuana, Y. Extracellular vesicles-based drug delivery system for cancer treatment. Cogent Med. 6, 1635806 (2019). · DOI
  56. Mehanny, M., Lehr, C.-M. & Fuhrmann, G. Extracellular vesicles as antigen carriers for novel vaccination avenues. Adv. Drug Deliv. Rev. 173, 164–180 (2021). · DOI
  57. 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). · DOI
  58. Thippabhotla, S., Zhong, C. & He, M. 3D cell culture stimulates the secretion of in vivo like extracellular vesicles. Sci. Rep. 9, 13012 (2019). · DOI
  59. Li, Y.-J. et al. Emerging strategies for labeling and tracking of extracellular vesicles. J. Control. Release 328, 141–159 (2020). · DOI
  60. de Abreu, R. C. et al. Native and bioengineered extracellular vesicles for cardiovascular therapeutics. Nat. Rev. Cardiol. 17, 685–697 (2020). · DOI
  61. Ikeda, G. et al. Mitochondria-rich extracellular vesicles from autologous stem cell-derived cardiomyocytes restore energetics of ischemic myocardium. J. Am. Coll. Cardiol. 77, 1073–1088 (2021). · DOI
  62. Villa, A. et al. Transplantation of autologous extracellular vesicles for cancer-specific targeting. Theranostics 11, 2034–2047 (2021). · DOI
  63. Escudier, B. et al. Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of the first phase I clinical trial. J. Transl. Med. 3, 10 (2005). · DOI
  64. Vulto, A. G. & Jaquez, O. A. The process defines the product: what really matters in biosimilar design and production? Rheumatology 56, iv14–iv29 (2017). · DOI
  65. Patel, D. B. et al. Impact of cell culture parameters on production and vascularization bioactivity of mesenchymal stem cell-derived extracellular vesicles. Bioeng. Transl. Med. 2, 170–179 (2017). · DOI
  66. Silverman, L. I. et al. Identifying and managing sources of variability in cell therapy manufacturing and clinical trials. Regen. Eng. Transl. Med. 5, 354–361 (2019). · DOI
  67. Iancu, E. M. & Kandalaft, L. E. Challenges and advantages of cell therapy manufacturing under Good Manufacturing Practices within the hospital setting. Curr. Opin. Biotechnol. 65, 233–241 (2020). · DOI
  68. Geigert, J. in The Challenge of CMC Regulatory Compliance for Biopharmaceuticals and Other Biologics (ed. Geigert, J.) 105–137 (Springer, 2013). · DOI
  69. Geigert, J. in The Challenge of CMC Regulatory Compliance for Biopharmaceuticals and Other Biologics (ed. Geigert, J.) 139–178 (Springer, 2013). · DOI
  70. Munagala, R., Aqil, F., Jeyabalan, J. & Gupta, R. C. Bovine milk-derived exosomes for drug delivery. Cancer Lett. 371, 48–61 (2016). · DOI
  71. 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). One of the first comprehensive examples of comparing different loading methods for various types of EV using a set of model compounds with varying water solubility. · DOI
  72. Schulz, E. et al. Biocompatible bacteria-derived vesicles show inherent antimicrobial activity. J. Control. Release 290, 46–55 (2018). · DOI
  73. Piffoux, M. et al. Extracellular vesicle production loaded with nanoparticles and drugs in a trade-off between loading, yield and purity: towards a personalized drug delivery system. Adv. Biosyst. 1, 1700044 (2017). · DOI
  74. Choi, H. et al. Exosome-based delivery of super-repressor IκBα relieves sepsis-associated organ damage and mortality. Sci. Adv. 6, eaaz6980 (2020). · DOI
  75. Meng, W. et al. Prospects and challenges of extracellular vesicle-based drug delivery system: considering cell source. Drug Deliv. 27, 585–598 (2020). · DOI · Paper page
  76. Lee, Y. X. F., Johansson, H., Wood, M. J. A. & El Andaloussi, S. Considerations and implications in the purification of extracellular vesicles—a cautionary tale. Front. Neurosci. 13, 1067 (2019). · DOI
  77. Auber, M., Fröhlich, D., Drechsel, O., Karaulanov, E. & Krämer-Albers, E.-M. Serum-free media supplements carry miRNAs that co-purify with extracellular vesicles. J. Extracell. Vesicles 8, 1656042 (2019). · DOI
  78. Nordin, J. Z. et al. Ultrafiltration with size-exclusion liquid chromatography for high yield isolation of extracellular vesicles preserving intact biophysical and functional properties. Nanomedicine 11, 879–883 (2015). · DOI
  79. Benedikter, B. J. et al. Ultrafiltration combined with size exclusion chromatography efficiently isolates extracellular vesicles from cell culture media for compositional and functional studies. Sci. Rep. 7, 15297 (2017). · DOI
  80. Corso, G. et al. Reproducible and scalable purification of extracellular vesicles using combined bind–elute and size exclusion chromatography. Sci. Rep. 7, 11561 (2017). · DOI
  81. Armstrong, J. P. K. & Stevens, M. M. Strategic design of extracellular vesicle drug delivery systems. Adv. Drug Deliv. Rev. 130, 12–16 (2018). · DOI · Paper page
  82. de Jong, O. G. et al. Drug delivery with extracellular vesicles: from imagination to innovation. Acc. Chem. Res. 52, 1761–1770 (2019). · DOI
  83. Luan, X. et al. Engineering exosomes as refined biological nanoplatforms for drug delivery. Acta Pharmacol. Sin. 38, 754–763 (2017). · DOI
  84. Sun, D. et al. A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes. Mol. Ther. 18, 1606–1614 (2010). · DOI
  85. Haney, M. J. et al. Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J. Control. Release 207, 18–30 (2015). · DOI · Paper page
  86. 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). · DOI · Paper page
  87. Fuhrmann, G. et al. Engineering extracellular vesicles with the tools of enzyme prodrug therapy. Adv. Mater. 30, 1706616 (2018). · DOI
  88. Piffoux, M., Silva, A. K. A., Wilhelm, C., Gazeau, F. & Tareste, D. Modification of extracellular vesicles by fusion with liposomes for the design of personalized biogenic drug delivery systems. ACS Nano 12, 6830–6842 (2018). This work gives a well studied example of controlled fusion of EVs with liposomes to enhance loading and surface functionalization of the vesicles. · DOI
  89. Hartjes, T. A., Mytnyk, S., Jenster, G. W., van Steijn, V. & van Royen, M. E. Extracellular vesicle quantification and characterization: common methods and emerging approaches. Bioengineering 6, 7 (2019). · DOI
  90. Deville, S. et al. Comparison of extracellular vesicle isolation and storage methods using high-sensitivity flow cytometry. PLoS ONE 16, e0245835 (2021). · DOI
  91. Paganini, C. et al. Scalable production and isolation of extracellular vesicles: available sources and lessons from current industrial bioprocesses. Biotechnol. J. 14, 1800528 (2019). · DOI
  92. Lőrincz, Á. M. et al. Effect of storage on physical and functional properties of extracellular vesicles derived from neutrophilic granulocytes. J. Extracell. Vesicles 3, 25465–25465 (2014). · DOI
  93. Keener, A. B. How extracellular vesicles can enhance drug delivery. Nature 582, S14–S15 (2020). · DOI
  94. Kojima, R. et al. Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson’s disease treatment. Nat. Commun. 9, 1305 (2018). · DOI · Paper page
  95. Rufino-Ramos, D. et al. Extracellular vesicles: novel promising delivery systems for therapy of brain diseases. J. Control. Release 262, 247–258 (2017). · DOI · Paper page
  96. Richter, M., Fuhrmann, K. & Fuhrmann, G. Evaluation of the storage stability of extracellular vesicles. J. Vis. Exp. (147), e59584 (2019). · DOI

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Metadata

Authors
Herrmann, I. K., Wood, M. J. A., & Fuhrmann, G.
Venue
Nature Nanotechnology
Publisher
Springer Science and Business Media LLC
Published
2021-07
Volume
16
Issue
7
Pages
748-759
ISSN
  • 1748-3387
  • 1748-3395
DOI
10.1038/s41565-021-00931-2
Cited by
1,948
References
13
Language
en
Licence
Funders
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (181290)
  • Bundesministerium für Bildung und Forschung (13XP5029A)

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