Skip to main content

Advertisement

SpringerLink
Log in

Modification of Extracellular Vesicle Surfaces: An Approach for Targeted Drug Delivery

  • Review Article
  • Published:
BioDrugs Aims and scope Submit manuscript

Abstract

Extracellular vesicles (EVs) are a promising drug delivery vehicle candidate because of their natural origin and intrinsic function of transporting various molecules between different cells. Several advantages of the EV delivery platform include enhanced permeability and retention effect, efficient interaction with recipient cells, the ability to traverse biological barriers, high biocompatibility, high biodegradability, and low immunogenicity. Furthermore, EV membranes share approximately similar structures and contents to the cell membrane, which allows surface modification of EVs, an approach to enable specific targeting. Enhanced drug accumulation in intended sites and reduced adverse effects of chemotherapeutic drugs are the most prominent effects of targeted drug delivery. In order to improve the targeting ability of EVs, chemical modification and genetic engineering are the most adopted methods to date. Diverse chemical methods are employed to decorate EV surfaces with various ligands such as aptamers, carbohydrates, peptides, vitamins, and antibodies. In this review, we introduce the biogenesis, content, and cellular pathway of natural EVs and further discuss the genetic modification of EVs, and its challenges. Furthermore, we provide a comprehensive deliberation on the various chemical modification methods for improved drug delivery, which are directly related to increasing the therapeutic index.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Kesharwani P, Taurin S, Greish K, editors. Theory and applications of nonparenteral nanomedicines. Amsterdam: Elsevier; 2020.

    Google Scholar 

  2. Wang Q, et al. Delivery of therapeutic agents by nanoparticles made of grapefruit-derived lipids. Nat Commun. 2013;4(1):1–13. https://doi.org/10.1038/ncomms2886.

    Article  CAS  Google Scholar 

  3. Gupta AK, Gupta M. Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials. 2005;26(18):3995–4021. https://doi.org/10.1016/j.biomaterials.2004.10.012.

    Article  CAS  PubMed  Google Scholar 

  4. Liu F, et al. Towards site-specific nanoparticles for drug delivery application: preparation, characterization and release performance. Chem Pap. 2017;71(12):2385–94. https://doi.org/10.1007/s11696-017-0233-5.

    Article  CAS  Google Scholar 

  5. He X, et al. A novel peptide probe for imaging and targeted delivery of liposomal doxorubicin to lung tumor. Mol Pharm. 2011;8(2):430–8. https://doi.org/10.1021/mp100266g.

    Article  CAS  PubMed  Google Scholar 

  6. Mitchell MJ, et al. Engineering precision nanoparticles for drug delivery. Nat Rev Drug Discovery. 2021;20(2):101–24. https://doi.org/10.1038/s41573-020-0090-8.

    Article  CAS  PubMed  Google Scholar 

  7. Andriyanov AV, et al. Therapeutic efficacy of combined PEGylated liposomal doxorubicin and radiofrequency ablation: comparing single and combined therapy in young and old mice. J Control Release. 2017;257:2–9. https://doi.org/10.1016/j.jconrel.2017.02.018.

    Article  CAS  PubMed  Google Scholar 

  8. Maier MA, et al. Biodegradable lipids enabling rapidly eliminated lipid nanoparticles for systemic delivery of RNAi therapeutics. Mol Ther. 2013;21(8):1570–8. https://doi.org/10.1038/mt.2013.124.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Torchilin VP. Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discovery. 2005;4(2):145–60. https://doi.org/10.1038/nrd1632.

    Article  CAS  PubMed  Google Scholar 

  10. Dolatabadi JEN, Omidi Y. Solid lipid-based nanocarriers as efficient targeted drug and gene delivery systems. TrAC Trends Anal Chem. 2016;77:100–8. https://doi.org/10.1016/j.trac.2015.12.016.

    Article  CAS  Google Scholar 

  11. Fenton OS, et al. Advances in biomaterials for drug delivery. Adv Mater. 2018;30(29):1705328. https://doi.org/10.1002/adma.201705328.

    Article  CAS  Google Scholar 

  12. Gomes-da-Silva LC, et al. Lipid-based nanoparticles for siRNA delivery in cancer therapy: paradigms and challenges. Acc Chem Res. 2012;45(7):1163–71. https://doi.org/10.1021/ar300048p.

    Article  CAS  PubMed  Google Scholar 

  13. Pardridge WM. Transport of small molecules through the blood-brain barrier: biology and methodology. Adv Drug Deliv Rev. 1995;15(1–3):5–36. https://doi.org/10.1016/0169-409X(95)00003-P.

    Article  CAS  PubMed  Google Scholar 

  14. Kim MS, et al. Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomed Nanotechnol Biol Med. 2016;12(3):655–64. https://doi.org/10.1016/j.nano.2015.10.012.

    Article  CAS  Google Scholar 

  15. Kim WJ, Kim SW. Efficient siRNA delivery with non-viral polymeric vehicles. Pharm Res. 2009;26(3):657–66. https://doi.org/10.1007/s11095-008-9774-1.

    Article  CAS  PubMed  Google Scholar 

  16. Simons M, Raposo G. Exosomes–vesicular carriers for intercellular communication. Curr Opin Cell Biol. 2009;21(4):575–81. https://doi.org/10.1007/s00441-012-1428-2.

    Article  CAS  PubMed  Google Scholar 

  17. Wei H, et al. A nanodrug consisting of doxorubicin and exosome derived from mesenchymal stem cells for osteosarcoma treatment in vitro. Int J Nanomed. 2019;14:8603. https://doi.org/10.2147/IJN.S218988.

    Article  CAS  Google Scholar 

  18. Sedykh SE, et al. Milk exosomes: isolation, biochemistry, morphology, and perspectives of use. Extracell Vesicles Import Hum Health. 2020. https://doi.org/10.5772/intechopen.85416.

    Article  Google Scholar 

  19. Wu M, et al. Isolation of exosomes from whole blood by integrating acoustics and microfluidics. Proc Natl Acad Sci. 2017;114(40):10584–9. https://doi.org/10.1073/pnas.1709210114.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. He L, et al. A highly efficient method for isolating urinary exosomes. Int J Mol Med. 2019;43(1):83–90. https://doi.org/10.3892/ijmm.2018.3944.

    Article  CAS  PubMed  Google Scholar 

  21. Bai R, et al. Induction of immune-related gene expression by seminal exosomes in the porcine endometrium. Biochem Biophys Res Commun. 2018;495(1):1094–101. https://doi.org/10.1016/J.BBRC.2017.11.100.

    Article  CAS  PubMed  Google Scholar 

  22. Zlotogorski-Hurvitz A, et al. Human saliva-derived exosomes: comparing methods of isolation. J Histochem Cytochem. 2015;63(3):181–9. https://doi.org/10.1369/0022155414564219.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Asea A, et al. Heat shock protein-containing exosomes in mid-trimester amniotic fluids. J Reprod Immunol. 2008;79(1):12–7. https://doi.org/10.1016/j.jri.2008.06.001.

    Article  CAS  PubMed  Google Scholar 

  24. Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013;200(4):373–83. https://doi.org/10.1083/jcb.201211138.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. 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. 2018;7(1):1535750. https://doi.org/10.1080/20013078.2018.1535750.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Johnstone R. Maturation of reticulocytes: formation of exosomes as a mechanism for shedding membrane proteins. Biochem Cell Biol. 1992;70(3–4):179–90. https://doi.org/10.1139/o92-028.

    Article  CAS  PubMed  Google Scholar 

  27. Mathivanan S, Simpson RJ. ExoCarta: A compendium of exosomal proteins and RNA. Proteomics. 2009;9(21):4997–5000. https://doi.org/10.1002/pmic.200900351.

    Article  CAS  PubMed  Google Scholar 

  28. Valadi H, et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9(6):654–9. https://doi.org/10.1038/ncb1596.

    Article  CAS  PubMed  Google Scholar 

  29. Llorente A, et al. Molecular lipidomics of exosomes released by PC-3 prostate cancer cells. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids. 2013;1831(7):1302–9. https://doi.org/10.1016/j.bbalip.2013.04.011.

    Article  CAS  PubMed  Google Scholar 

  30. Blanco E, Shen H, Ferrari M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat Biotechnol. 2015;33(9):941–51. https://doi.org/10.1038/nbt.3330.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lu M, et al. Comparison of exosome-mimicking liposomes with conventional liposomes for intracellular delivery of siRNA. Int J Pharm. 2018;550(1–2):100–13. https://doi.org/10.1016/j.ijpharm.2018.08.040.

    Article  CAS  PubMed  Google Scholar 

  32. Haney MJ, et al. Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J Control Release. 2015;207:18–30. https://doi.org/10.1016/j.jconrel.2015.03.033.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. El-Andaloussi S, et al. Exosome-mediated delivery of siRNA in vitro and in vivo. Nat Protoc. 2012;7(12):2112–26. https://doi.org/10.1038/nprot.2012.131.

    Article  CAS  PubMed  Google Scholar 

  34. Sun D, et al. A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes. Mol Ther. 2010;18(9):1606–14. https://doi.org/10.1038/mt.2010.105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Somiya M, Yoshioka Y, Ochiya T. Biocompatibility of highly purified bovine milk-derived extracellular vesicles. J Extracell Vesicles. 2018;7(1):1440132. https://doi.org/10.1080/20013078.2018.1440132.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Kumar S, et al. Cloaked exosomes: biocompatible, durable, and degradable encapsulation. Small. 2018;14(34):1802052. https://doi.org/10.1002/smll.201802052.

    Article  CAS  Google Scholar 

  37. Lv L-H, et al. Anticancer drugs cause release of exosomes with heat shock proteins from human hepatocellular carcinoma cells that elicit effective natural killer cell antitumor responses in vitro. J Biol Chem. 2012;287(19):15874–85. https://doi.org/10.1074/jbc.M112.340588.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Shyong Y-J, Chang K-C, Lin F-H. Calcium phosphate particles stimulate exosome secretion from phagocytes for the enhancement of drug delivery. Colloids Surf B. 2018;171:391–7. https://doi.org/10.1016/j.colsurfb.2018.07.037.

    Article  CAS  Google Scholar 

  39. Panigrahi GK, et al. Hypoxia-induced exosome secretion promotes survival of African-American and Caucasian prostate cancer cells. Sci Rep. 2018;8(1):1–13. https://doi.org/10.1038/s41598-018-22068-4.

    Article  CAS  Google Scholar 

  40. Chinnappan M, et al. Exosomes as drug delivery vehicle and contributor of resistance to anticancer drugs. Cancer Lett. 2020;486:18–28. https://doi.org/10.1016/j.canlet.2020.05.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Lai CP, et al. Dynamic biodistribution of extracellular vesicles in vivo using a multimodal imaging reporter. ACS Nano. 2014;8(1):483–94. https://doi.org/10.1021/nn404945r.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Wiklander OP, et al. Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting. J Extracell Vesicles. 2015;4(1):26316. https://doi.org/10.3402/jev.v4.26316.

    Article  PubMed  Google Scholar 

  43. Das CK, et al. Exosome as a novel shuttle for delivery of therapeutics across biological barriers. Mol Pharm. 2018;16(1):24–40. https://doi.org/10.1021/acs.molpharmaceut.8b00901.

    Article  CAS  PubMed  Google Scholar 

  44. Gilligan KE, Dwyer RM. Engineering exosomes for cancer therapy. Int J Mol Sci. 2017;18(6):1122. https://doi.org/10.3390/ijms18061122.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Tian T, et al. Surface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy. Biomaterials. 2018;150:137–49.

    Article  CAS  PubMed  Google Scholar 

  46. Pan B-T, Johnstone RM. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell. 1983;33(3):967–78. https://doi.org/10.1016/0092-8674(83)90040-5.

    Article  CAS  PubMed  Google Scholar 

  47. Harding C, Stahl P. Transferrin recycling in reticulocytes: pH and iron are important determinants of ligand binding and processing. Biochem Biophys Res Commun. 1983;113(2):650–8. https://doi.org/10.1016/0006-291X(83)91776-X.

    Article  CAS  PubMed  Google Scholar 

  48. Johnstone RM, et al. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem. 1987;262(19):9412–20. https://doi.org/10.1016/S0021-9258(18)48095-7.

    Article  CAS  PubMed  Google Scholar 

  49. Pan B-T, et al. Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes. J Cell Biol. 1985;101(3):942–8. https://doi.org/10.1083/jcb.101.3.942.

    Article  CAS  PubMed  Google Scholar 

  50. Johnstone R, et al. Exosome formation during maturation of mammalian and avian reticulocytes: evidence that exosome release is a major route for externalization of obsolete membrane proteins. J Cell Physiol. 1991;147(1):27–36. https://doi.org/10.1002/jcp.1041470105.

    Article  CAS  PubMed  Google Scholar 

  51. Raposo G, et al. B lymphocytes secrete antigen-presenting vesicles. J Exp Med. 1996;183(3):1161–72. https://doi.org/10.1084/jem.183.3.1161.

    Article  CAS  PubMed  Google Scholar 

  52. Zitvogel L, et al. Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell derived exosomes. Nat Med. 1998;4(5):594–600. https://doi.org/10.1038/nm0598-594.

    Article  CAS  PubMed  Google Scholar 

  53. Crawford N. The presence of contractile proteins in platelet microparticles isolated from human and animal platelet-free plasma. Br J Haematol. 1971;21(1):53–69. https://doi.org/10.1111/j.1365-2141.1971.tb03416.x.

    Article  CAS  PubMed  Google Scholar 

  54. Fourcade O, et al. Secretory phospholipase A2 generates the novel lipid mediator lysophosphatidic acid in membrane microvesicles shed from activated cells. Cell. 1995;80(6):919–27. https://doi.org/10.1016/0092-8674(95)90295-3.

    Article  CAS  PubMed  Google Scholar 

  55. Théry C, et al. Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles. J Immunol. 2001;166(12):7309–18. https://doi.org/10.4049/jimmunol.166.12.7309.

    Article  PubMed  Google Scholar 

  56. Gawrisch K, et al. The rate of lateral diffusion of phospholipids in erythrocyte microvesicles. Biochimica et Biophysica Acta (BBA)-Biomembranes. 1986;856(3):443–7. https://doi.org/10.1016/0005-2736(86)90135-5.

    Article  CAS  PubMed  Google Scholar 

  57. Subra C, et al. Exosome lipidomics unravels lipid sorting at the level of multivesicular bodies. Biochimie. 2007;89(2):205–12. https://doi.org/10.1016/j.biochi.2006.10.014.

    Article  CAS  PubMed  Google Scholar 

  58. Ratajczak J, et al. Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia. 2006;20(5):847–56. https://doi.org/10.1038/sj.leu.2404132.

    Article  CAS  PubMed  Google Scholar 

  59. Skog J, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008;10(12):1470–6. https://doi.org/10.1038/ncb1800.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Luo X, et al. High-performance chemical isotope labeling liquid chromatography mass spectrometry for exosome metabolomics. Anal Chem. 2018;90(14):8314–9. https://doi.org/10.1021/acs.analchem.8b01726.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Van Niel G, et al. Exosomes: a common pathway for a specialized function. J Biochem. 2006;140(1):13–21. https://doi.org/10.1093/jb/mvj128.

    Article  CAS  PubMed  Google Scholar 

  62. Caponnetto F, et al. The miRNA content of exosomes released from the glioma microenvironment can affect malignant progression. Biomedicines. 2020;8(12):564. https://doi.org/10.3390/biomedicines8120564.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Trajkovic K, et al. Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science. 2008;319(5867):1244–7. https://doi.org/10.1126/science.1153124.

    Article  CAS  PubMed  Google Scholar 

  64. Wei X, et al. Surface phosphatidylserine is responsible for the internalization on microvesicles derived from hypoxia-induced human bone marrow mesenchymal stem cells into human endothelial cells. PLoS ONE. 2016;11(1): e0147360. https://doi.org/10.1371/journal.pone.0147360.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Sobo-Vujanovic A, Munich S, Vujanovic NL. Dendritic-cell exosomes cross-present Toll-like receptor-ligands and activate bystander dendritic cells. Cell Immunol. 2014;289(1–2):119–27. https://doi.org/10.1016/j.cellimm.2014.03.016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Montecalvo A, et al. Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood J Am Soc Hematol. 2012;119(3):756–66. https://doi.org/10.1182/blood-2011-02-338004.

    Article  CAS  Google Scholar 

  67. Escrevente C, et al. Interaction and uptake of exosomes by ovarian cancer cells. BMC Cancer. 2011;11(1):1–10. https://doi.org/10.1186/1471-2407-11-108.

    Article  CAS  Google Scholar 

  68. Eguchi S, et al. Cardiomyocytes capture stem cell-derived, anti-apoptotic microRNA-214 via clathrin-mediated endocytosis in acute myocardial infarction. J Biol Chem. 2019;294(31):11665–74. https://doi.org/10.3390/cells11223664.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Delenclos M, et al. Investigation of endocytic pathways for the internalization of exosome-associated oligomeric alpha-synuclein. Front Neurosci. 2017;11:172. https://doi.org/10.3389/fnins.2017.00172.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Nanbo A, et al. Exosomes derived from Epstein-Barr virus-infected cells are internalized via caveola-dependent endocytosis and promote phenotypic modulation in target cells. J Virol. 2013;87(18):10334–47. https://doi.org/10.1128/JVI.01310-13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Feng D, et al. Cellular internalization of exosomes occurs through phagocytosis. Traffic. 2010;11(5):675–87. https://doi.org/10.1111/j.1600-0854.2010.01041.x.

    Article  CAS  PubMed  Google Scholar 

  72. Kamerkar S, et al. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature. 2017;546(7659):498–503. https://doi.org/10.1038/nature22341.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Komuro H, et al. Engineering extracellular vesicles to target pancreatic tissue in vivo. Nanotheranostics. 2021;5(4):378. https://doi.org/10.7150/ntno.54879.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Li S, et al. Engineering macrophage-derived exosomes for targeted chemotherapy of triple-negative breast cancer. Nanoscale. 2020;12(19):10854–62. https://doi.org/10.1016/j.nano.2017.09.011.

    Article  CAS  PubMed  Google Scholar 

  75. Alvarez-Erviti L, et al. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 2011;29(4):341–5. https://doi.org/10.1038/nbt.1807.

    Article  CAS  PubMed  Google Scholar 

  76. Ohno S-I, et al. Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol Ther. 2013;21(1):185–91. https://doi.org/10.1038/mt.2012.180.

    Article  CAS  PubMed  Google Scholar 

  77. Longatti A, et al. High affinity single-chain variable fragments are specific and versatile targeting motifs for extracellular vesicles. Nanoscale. 2018;10(29):14230–44. https://doi.org/10.1039/C8NR03970D.

    Article  CAS  PubMed  Google Scholar 

  78. Liang G, et al. Engineered exosome-mediated delivery of functionally active miR-26a and its enhanced suppression effect in HepG2 cells. Int J Nanomed. 2018;13:585. https://doi.org/10.2147/IJN.S154458.

    Article  CAS  Google Scholar 

  79. Cheng Q, et al. Expanding the toolbox of exosome-based modulators of cell functions. Biomaterials. 2021;277: 121129. https://doi.org/10.1016/j.biomaterials.2021.121129.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Tian Y, et al. A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Biomaterials. 2014;35(7):2383–90. https://doi.org/10.1016/j.biomaterials.2013.11.083.

    Article  CAS  PubMed  Google Scholar 

  81. Bai J, et al. Engineered targeting tLyp-1 exosomes as gene therapy vectors for efficient delivery of siRNA into lung cancer cells. Asian J Pharm Sci. 2020;15(4):461–71. https://doi.org/10.1016/j.ajps.2019.04.002.

    Article  PubMed  Google Scholar 

  82. Yu Y, et al. Genetically engineered exosomes display RVG peptide and selectively enrich a neprilysin variant: a potential formulation for the treatment of Alzheimer’s disease. J Drug Target. 2021;29(10):1128–38. https://doi.org/10.1080/1061186X.2021.1929257.

    Article  CAS  PubMed  Google Scholar 

  83. Tomanin R, Scarpa M. Why do we need new gene therapy viral vectors? Characteristics, limitations and future perspectives of viral vector transduction. Curr Gene Ther. 2004;4(4):357–72. https://doi.org/10.2174/1566523043346011.

    Article  CAS  PubMed  Google Scholar 

  84. Gomari H, Moghadam MF, Soleimani M. Targeted cancer therapy using engineered exosome as a natural drug delivery vehicle. Onco Targets Ther. 2018;11:5753. https://doi.org/10.2147/OTT.S173110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Jang SC, et al. Bioinspired exosome-mimetic nanovesicles for targeted delivery of chemotherapeutics to malignant tumors. ACS Nano. 2013;7(9):7698–710. https://doi.org/10.1021/nn402232g.

    Article  CAS  PubMed  Google Scholar 

  86. Jo W, et al. Large-scale generation of cell-derived nanovesicles. Nanoscale. 2014;6(20):12056–64. https://doi.org/10.1039/C4NR02391A.

    Article  CAS  PubMed  Google Scholar 

  87. Severic M, et al. Genetically-engineered anti-PSMA exosome mimetics targeting advanced prostate cancer in vitro and in vivo. J Control Release. 2021;330:101–10. https://doi.org/10.1016/j.jconrel.2020.12.017.

    Article  CAS  PubMed  Google Scholar 

  88. Wang C, et al. Engineering a HEK-293T exosome-based delivery platform for efficient tumor-targeting chemotherapy/internal irradiation combination therapy. J Nanobiotechnol. 2022;20(1):247. https://doi.org/10.1186/s12951-022-01462-1.

    Article  CAS  Google Scholar 

  89. Mentkowski KI, Lang JK. Exosomes engineered to express a cardiomyocyte binding peptide demonstrate improved cardiac retention in vivo. Sci Rep. 2019;9(1):1–13. https://doi.org/10.1038/s41598-019-46407-1.

    Article  CAS  Google Scholar 

  90. Liang G, et al. Engineered exosomes for targeted co-delivery of miR-21 inhibitor and chemotherapeutics to reverse drug resistance in colon cancer. J Nanobiotechnol. 2020;18(1):1–15. https://doi.org/10.1186/s12951-019-0563-2.

    Article  CAS  Google Scholar 

  91. Liang Y, et al. Chondrocyte-targeted microRNA delivery by engineered exosomes toward a cell-free osteoarthritis therapy. ACS Appl Mater Interfaces. 2020;12(33):36938–47. https://doi.org/10.1021/acsami.0c10458.

    Article  CAS  PubMed  Google Scholar 

  92. Cheng Q, et al. Reprogramming exosomes as nanoscale controllers of cellular immunity. J Am Chem Soc. 2018;140(48):16413–7. https://doi.org/10.1021/jacs.8b10047.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Bose RJ, et al. Engineered cell-derived vesicles displaying targeting peptide and functionalized with nanocarriers for therapeutic microRNA delivery to triple-negative breast cancer in mice. Adv Healthcare Mater. 2022;11(5):2101387. https://doi.org/10.1002/adhm.202270026.

    Article  CAS  Google Scholar 

  94. Komuro H, et al. Design and evaluation of engineered extracellular vesicle (EV)-based targeting for EGFR-overexpressing tumor cells using monobody display. Bioengineering. 2022;9(2):56. https://doi.org/10.3390/bioengineering9020056.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Mai J, et al. αvβ3-targeted sEVs for efficient intracellular delivery of proteins using MFG-E8. BMC Biotechnol. 2022;22(1):1–10. https://doi.org/10.1186/s12896-022-00745-7.

    Article  CAS  Google Scholar 

  96. Limoni SK, et al. Engineered exosomes for targeted transfer of siRNA to HER2 positive breast cancer cells. Appl Biochem Biotechnol. 2019;187(1):352–64. https://doi.org/10.1007/s12010-018-2813-4.

    Article  CAS  PubMed  Google Scholar 

  97. Bellavia D, et al. Interleukin 3-receptor targeted exosomes inhibit in vitro and in vivo Chronic Myelogenous Leukemia cell growth. Theranostics. 2017;7(5):1333. https://doi.org/10.7150/thno.17092.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Mahati S, et al. Delivery of miR-26a using an exosomes-based nanosystem inhibited proliferation of hepatocellular carcinoma. Front Mol Biosci. 2021. https://doi.org/10.3389/fmolb.2021.738219.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Kim G, et al. Engineering exosomes for pulmonary delivery of peptides and drugs to inflammatory lung cells by inhalation. J Control Release. 2021;330:684–95. https://doi.org/10.1016/j.jconrel.2020.12.053.

    Article  CAS  PubMed  Google Scholar 

  100. Huang L, et al. Engineered exosomes as an in situ DC-primed vaccine to boost antitumor immunity in breast cancer. Mol Cancer. 2022;21(1):1–19. https://doi.org/10.1186/s12943-022-01515-x.

    Article  CAS  Google Scholar 

  101. Zhai Y, et al. High-efficiency brain-targeted intranasal delivery of BDNF mediated by engineered exosomes to promote remyelination. Biomater Sci. 2022;10(19):5707–18. https://doi.org/10.1039/d2bm00518b.

    Article  CAS  PubMed  Google Scholar 

  102. Gečys D, et al. Internalisation of RGD-engineered extracellular vesicles by glioblastoma cells. Biology. 2022;11(10):1483. https://doi.org/10.3390/biology11101483.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Kooijmans SA, et al. Modulation of tissue tropism and biological activity of exosomes and other extracellular vesicles: new nanotools for cancer treatment. Pharmacol Res. 2016;111:487–500. https://doi.org/10.1016/j.phrs.2016.07.006.

    Article  CAS  PubMed  Google Scholar 

  104. Smyth T, et al. Surface functionalization of exosomes using click chemistry. Bioconjug Chem. 2014;25(10):1777–84. https://doi.org/10.1021/bc500291r.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Komuro H, et al. Advances of engineered extracellular vesicles-based therapeutics strategy. Sci Technol Adv Mater. 2022. https://doi.org/10.1080/14686996.2022.2133342.

    Article  PubMed  PubMed Central  Google Scholar 

  106. Song S, et al. In situ one-step fluorescence labeling strategy of exosomes via bioorthogonal click chemistry for real-time exosome tracking in vitro and in vivo. Bioconjug Chem. 2020;31(5):1562–74. https://doi.org/10.1021/acs.bioconjchem.0c00216.

    Article  CAS  PubMed  Google Scholar 

  107. Armstrong JP, Holme MN, Stevens MM. Re-engineering extracellular vesicles as smart nanoscale therapeutics. ACS Nano. 2017;11(1):69–83. https://doi.org/10.1021/acsnano.6b07607.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Fan Y, et al. Responsive dual-targeting exosome as a drug carrier for combination cancer immunotherapy. Research. 2021. https://doi.org/10.34133/2021/9862876.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Kooijmans SA, et al. Recombinant phosphatidylserine-binding nanobodies for targeting of extracellular vesicles to tumor cells: a plug-and-play approach. Nanoscale. 2018;10(5):2413–26. https://doi.org/10.1039/c7nr06966a.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Si Y, et al. Targeted exosomes for drug delivery: biomanufacturing, surface tagging, and validation. Biotechnol J. 2020;15(1):1900163. https://doi.org/10.1002/biot.201900163.

    Article  CAS  Google Scholar 

  111. Kooijmans S, et al. PEGylated and targeted extracellular vesicles display enhanced cell specificity and circulation time. J Control Release. 2016;224:77–85. https://doi.org/10.1016/j.jconrel.2016.01.009.

    Article  CAS  PubMed  Google Scholar 

  112. Guo L, et al. Surface-modified engineered exosomes attenuated cerebral ischemia/reperfusion injury by targeting the delivery of quercetin towards impaired neurons. J Nanobiotechnol. 2021;19(1):1–15. https://doi.org/10.1186/s12951-021-00879-4.

    Article  CAS  Google Scholar 

  113. Ye Z, et al. Methotrexate-loaded extracellular vesicles functionalized with therapeutic and targeted peptides for the treatment of glioblastoma multiforme. ACS Appl Mater Interfaces. 2018;10(15):12341–50. https://doi.org/10.1021/acsami.7b18135.

    Article  CAS  PubMed  Google Scholar 

  114. Zhu Q, et al. Embryonic stem cells-derived exosomes endowed with targeting properties as chemotherapeutics delivery vehicles for glioblastoma therapy. Adv Sci. 2019;6(6):1801899. https://doi.org/10.1002/advs.201801899.

    Article  CAS  Google Scholar 

  115. Huang X, et al. Engineered exosome as targeted lncRNA MEG3 delivery vehicles for osteosarcoma therapy. J Control Release. 2022;343:107–17. https://doi.org/10.1016/j.jconrel.2022.01.026.

    Article  CAS  PubMed  Google Scholar 

  116. Cao Y, et al. Engineered exosome-mediated near-infrared-II region V2C quantum dot delivery for nucleus-target low-temperature photothermal therapy. ACS Nano. 2019;13(2):1499–510. https://doi.org/10.1021/acsnano.8b07224.

    Article  CAS  PubMed  Google Scholar 

  117. Vandergriff A, et al. Targeting regenerative exosomes to myocardial infarction using cardiac homing peptide. Theranostics. 2018;8(7):1869. https://doi.org/10.7150/thno.20524.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Cheng H, et al. Chimeric peptide engineered exosomes for dual-stage light guided plasma membrane and nucleus targeted photodynamic therapy. Biomaterials. 2019;211:14–24. https://doi.org/10.1016/j.biomaterials.2019.05.004.

    Article  CAS  PubMed  Google Scholar 

  119. Cui G-H, et al. RVG-modified exosomes derived from mesenchymal stem cells rescue memory deficits by regulating inflammatory responses in a mouse model of Alzheimer’s disease. Immunity Ageing. 2019;16(1):1–12. https://doi.org/10.1186/s12979-019-0150-2.

    Article  CAS  Google Scholar 

  120. Cui Y, et al. A bone-targeted engineered exosome platform delivering siRNA to treat osteoporosis. Bioactive Mater. 2022;10:207–21. https://doi.org/10.1016/j.bioactmat.2021.09.015.

    Article  CAS  Google Scholar 

  121. Tian T, et al. Targeted delivery of neural progenitor cell-derived extracellular vesicles for anti-inflammation after cerebral ischemia. Theranostics. 2021;11(13):6507. https://doi.org/10.7150/thno.56367.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Liang S, Xu H, Ye B-C. Membrane-decorated exosomes for combination drug delivery and improved glioma therapy. Langmuir. 2021;38(1):299–308. https://doi.org/10.1021/acs.langmuir.1c02500.

    Article  CAS  PubMed  Google Scholar 

  123. Kanada M, et al. A dual-reporter platform for screening tumor-targeted extracellular vesicles. Pharmaceutics. 2022;14(3):475. https://doi.org/10.3390/pharmaceutics14030475.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Rong Y, et al. Engineered extracellular vesicles for delivery of siRNA promoting targeted repair of traumatic spinal cord injury. Bioactive Mater. 2023;23:328–42. https://doi.org/10.1016/j.bioactmat.2022.11.011.

    Article  CAS  Google Scholar 

  125. Pullan J, et al. Modified bovine milk exosomes for doxorubicin delivery to triple-negative breast cancer cells. ACS Appl Bio Mater. 2022;5(5):2163–75. https://doi.org/10.1021/acsabm.2c00015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Li D, et al. Hyaluronan decoration of milk exosomes directs tumor-specific delivery of doxorubicin. Carbohydr Res. 2020;493: 108032. https://doi.org/10.1016/j.carres.2020.108032.

    Article  CAS  PubMed  Google Scholar 

  127. Liu J, et al. Functional extracellular vesicles engineered with lipid-grafted hyaluronic acid effectively reverse cancer drug resistance. Biomaterials. 2019;223: 119475. https://doi.org/10.1016/j.biomaterials.2019.119475.

    Article  CAS  PubMed  Google Scholar 

  128. Choi ES, et al. Mannose-modified serum exosomes for the elevated uptake to murine dendritic cells and lymphatic accumulation. Macromol Biosci. 2019;19(7):1900042. https://doi.org/10.1002/mabi.201900042.

    Article  CAS  Google Scholar 

  129. Yang X, et al. Eradicating intracellular MRSA via targeted delivery of lysostaphin and vancomycin with mannose-modified exosomes. J Control Release. 2021;329:454–67. https://doi.org/10.1016/j.jconrel.2020.11.045.

    Article  CAS  PubMed  Google Scholar 

  130. Tamura R, Uemoto S, Tabata Y. Augmented liver targeting of exosomes by surface modification with cationized pullulan. Acta Biomater. 2017;57:274–84. https://doi.org/10.1016/j.actbio.2017.05.013.

    Article  CAS  PubMed  Google Scholar 

  131. Zou J, et al. Aptamer-functionalized exosomes: elucidating the cellular uptake mechanism and the potential for cancer-targeted chemotherapy. Anal Chem. 2019;91(3):2425–30. https://doi.org/10.1021/acs.analchem.8b05204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Pi F, et al. Nanoparticle orientation to control RNA loading and ligand display on extracellular vesicles for cancer regression. Nat Nanotechnol. 2018;13(1):82–9. https://doi.org/10.1038/s41565-017-0012-z.

    Article  CAS  PubMed  Google Scholar 

  133. Tran PH, et al. Aspirin-loaded nanoexosomes as cancer therapeutics. Int J Pharm. 2019;572: 118786. https://doi.org/10.1016/j.ijpharm.2019.118786.

    Article  CAS  PubMed  Google Scholar 

  134. Luo C, et al. Biomimetic carriers based on giant membrane vesicles for targeted drug delivery and photodynamic/photothermal synergistic therapy. ACS Appl Mater Interfaces. 2019;11(47):43811–9. https://doi.org/10.1021/acsami.9b11223.

    Article  CAS  PubMed  Google Scholar 

  135. Wang Y, et al. Nucleolin-targeted extracellular vesicles as a versatile platform for biologics delivery to breast cancer. Theranostics. 2017;7(5):1360. https://doi.org/10.7150/thno.16532.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Bagheri E, et al. Targeted doxorubicin-loaded mesenchymal stem cells-derived exosomes as a versatile platform for fighting against colorectal cancer. Life Sci. 2020;261: 118369. https://doi.org/10.1016/j.lfs.2020.118369.

    Article  CAS  PubMed  Google Scholar 

  137. Li Z, et al. Non-small-cell lung cancer regression by siRNA delivered through exosomes that display EGFR RNA aptamer. Nucleic Acid Therap. 2021;31(5):364–74. https://doi.org/10.1089/nat.2021.0002.

    Article  CAS  Google Scholar 

  138. Shamili FH, et al. Immunomodulatory properties of MSC-derived exosomes armed with high affinity aptamer toward mylein as a platform for reducing multiple sclerosis clinical score. J Control Release. 2019;299:149–64. https://doi.org/10.1016/j.jconrel.2019.02.032.

    Article  CAS  Google Scholar 

  139. Huang H, et al. Edible and cation-free kiwi fruit derived vesicles mediated EGFR-targeted siRNA delivery to inhibit multidrug resistant lung cancer. J Nanobiotechnol. 2023;21(1):1–14. https://doi.org/10.1186/s12951-023-01766-w.

    Article  CAS  Google Scholar 

  140. Zheng Z, et al. Folate-displaying exosome mediated cytosolic delivery of siRNA avoiding endosome trapping. J Control Release. 2019;311:43–9. https://doi.org/10.1016/j.jconrel.2019.08.021.

    Article  CAS  PubMed  Google Scholar 

  141. Yu M, et al. Targeted exosome-encapsulated erastin induced ferroptosis in triple negative breast cancer cells. Cancer Sci. 2019;110(10):3173–82. https://doi.org/10.1111/cas.14181.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Nguyen Cao TG, et al. Safe and targeted sonodynamic cancer therapy using biocompatible exosome-based nanosonosensitizers. ACS Appl Mater Interfaces. 2021;13(22):25575–88. https://doi.org/10.1021/acsami.0c22883.

    Article  CAS  PubMed  Google Scholar 

  143. Aqil F, et al. Milk exosomes-natural nanoparticles for siRNA delivery. Cancer Lett. 2019;449:186–95. https://doi.org/10.1016/j.canlet.2019.02.011.

    Article  CAS  PubMed  Google Scholar 

  144. Yan F, et al. Exosome-based biomimetic nanoparticles targeted to inflamed joints for enhanced treatment of rheumatoid arthritis. J Nanobiotechnol. 2020;18(1):1–15. https://doi.org/10.1186/s12951-020-00675-6.

    Article  CAS  Google Scholar 

  145. Jiang L, et al. A post-insertion strategy for surface functionalization of bacterial and mammalian cell-derived extracellular vesicles. Biochimica et Biophysica Acta (BBA)-General Subjects. 2021;1865(4): 129763. https://doi.org/10.1016/j.bbagen.2020.129763.

    Article  CAS  PubMed  Google Scholar 

  146. Wang J, et al. Chemically edited exosomes with dual ligand purified by microfluidic device for active targeted drug delivery to tumor cells. ACS Appl Mater Interfaces. 2017;9(33):27441–52. https://doi.org/10.1021/acsami.7b06464.

    Article  CAS  PubMed  Google Scholar 

  147. Arslan FB, Atar KO, Calis S. Antibody-mediated drug delivery. Int J Pharm. 2021;596: 120268. https://doi.org/10.1016/j.ijpharm.2021.120268.

    Article  CAS  PubMed  Google Scholar 

  148. Shi C, et al. Novel drug delivery liposomes targeted with a fully human anti-VEGF165 monoclonal antibody show superior antitumor efficacy in vivo. Biomed Pharmacother. 2015;73:48–57. https://doi.org/10.1016/j.biopha.2015.05.008.

    Article  CAS  PubMed  Google Scholar 

  149. Lu L, et al. Antibody-modified liposomes for tumor-targeting delivery of timosaponin AIII. Int J Nanomed. 2018;13:1927. https://doi.org/10.2147/IJN.S153107.

    Article  CAS  Google Scholar 

  150. Nejadmoghaddam M-R, et al. Antibody-drug conjugates: possibilities and challenges. Avicenna J Med Biotechnol. 2019;11(1):3.

    PubMed  PubMed Central  Google Scholar 

  151. Drake C. Combination immunotherapy approaches. Ann Oncol. 2012;23:41–6. https://doi.org/10.1093/annonc/mds262.

    Article  Google Scholar 

  152. Dolk E, et al. Induced refolding of a temperature denatured llama heavy-chain antibody fragment by its antigen. PROTEINS Struct Funct Bioinform. 2005;59(3):555–64. https://doi.org/10.1002/prot.20378.

    Article  CAS  Google Scholar 

  153. Wang AZ, et al. Biofunctionalized targeted nanoparticles for therapeutic applications. Expert Opin Biol Ther. 2008;8(8):1063–70. https://doi.org/10.1517/14712598.8.8.1063.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Salunkhe S, et al. Surface functionalization of exosomes for target-specific delivery and in vivo imaging & tracking: strategies and significance. J Control Release. 2020. https://doi.org/10.1016/j.jconrel.2020.07.042.

    Article  PubMed  Google Scholar 

  155. Dintzis HM. Assembly of the peptide chains of hemoglobin. Proc Natl Acad Sci. 1961;47(3):247–61. https://doi.org/10.1073/pnas.47.3.247.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Jia G, et al. NRP-1 targeted and cargo-loaded exosomes facilitate simultaneous imaging and therapy of glioma in vitro and in vivo. Biomaterials. 2018;178:302–16. https://doi.org/10.1016/j.biomaterials.2018.06.029.

    Article  CAS  PubMed  Google Scholar 

  157. Lee H, et al. pH-responsive hyaluronate-anchored extracellular vesicles to promote tumor-targeted drug delivery. Carbohyd Polym. 2018;202:323–33. https://doi.org/10.1016/j.carbpol.2018.08.141.

    Article  CAS  Google Scholar 

  158. Saneja A, et al. CD44 targeted PLGA nanomedicines for cancer chemotherapy. Eur J Pharm Sci. 2018;121:47–58. https://doi.org/10.1016/j.ejps.2018.05.012.

    Article  CAS  PubMed  Google Scholar 

  159. Johannssen T, Lepenies B. Glycan-based cell targeting to modulate immune responses. Trends Biotechnol. 2017;35(4):334–46. https://doi.org/10.1016/j.tibtech.2016.10.002.

    Article  CAS  PubMed  Google Scholar 

  160. Kanatani I, et al. Efficient gene transfer by pullulan–spermine occurs through both clathrin-and raft/caveolae-dependent mechanisms. J Control Release. 2006;116(1):75–82. https://doi.org/10.1016/j.jconrel.2006.09.001.

    Article  CAS  PubMed  Google Scholar 

  161. Jo J-I, et al. Liver targeting of plasmid DNA with a cationized pullulan for tumor suppression. J Nanosci Nanotechnol. 2006;6(9–10):2853–9. https://doi.org/10.1166/jnn.2006.466.

    Article  CAS  PubMed  Google Scholar 

  162. Zhou J, Rossi J. Aptamers as targeted therapeutics: current potential and challenges. Nat Rev Drug Discovery. 2017;16(3):181–202. https://doi.org/10.1038/nrd.2016.199.

    Article  CAS  PubMed  Google Scholar 

  163. Fang X, Tan W. Aptamers generated from cell-SELEX for molecular medicine: a chemical biology approach. Acc Chem Res. 2010;43(1):48–57. https://doi.org/10.1021/ar900101s.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Tan W, Fang X. Aptamers selected by cell-SELEX for theranostics. New York: Springer; 2015.

    Book  Google Scholar 

  165. Xiong X, et al. DNA Aptamer-Mediated Cell Targeting. Angew Chem. 2013;125(5):1512–6. https://doi.org/10.1002/anie.201207063.

    Article  CAS  Google Scholar 

  166. Liu H, et al. DNA-based micelles: synthesis, micellar properties and size-dependent cell permeability. Chem A Eur J. 2010;16(12):3791–7. https://doi.org/10.1002/chem.200901546.

    Article  CAS  Google Scholar 

  167. Wan Y, et al. Aptamer-conjugated extracellular nanovesicles for targeted drug delivery. Can Res. 2018;78(3):798–808. https://doi.org/10.1158/0008-5472.CAN-17-2880.

    Article  CAS  Google Scholar 

  168. Pi F. RNA Nanotechnology for Next Generation Targeted Drug Delivery. 2016. https://doi.org/10.13023/ETD.2016.432.

    Article  Google Scholar 

  169. Lu J, et al. Targeted delivery of doxorubicin by folic acid-decorated dual functional nanocarrier. Mol Pharm. 2014;11(11):4164–78. https://doi.org/10.1021/mp500389v.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Perillo B, et al. ROS in cancer therapy: The bright side of the moon. Exp Mol Med. 2020;52(2):192–203. https://doi.org/10.1038/s12276-020-0384-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Wu S-K, et al. MR-guided focused ultrasound facilitates sonodynamic therapy with 5-aminolevulinic acid in a rat glioma model. Sci Rep. 2019;9(1):1–10. https://doi.org/10.1038/s41598-019-46832-2.

    Article  CAS  Google Scholar 

  172. Pollalis D, et al. Intraocular RGD-Engineered Exosomes and Active Targeting of Choroidal Neovascularization (CNV). Cells. 2022;11(16):2573. https://doi.org/10.3390/cells11162573.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Kim MS, et al. Engineering macrophage-derived exosomes for targeted paclitaxel delivery to pulmonary metastases: in vitro and in vivo evaluations. Nanomed Nanotechnol Biol Med. 2018;14(1):195–204. https://doi.org/10.1016/j.nano.2017.09.011.

    Article  CAS  Google Scholar 

  174. Whitford W, Guterstam P. Exosome manufacturing status. Future Med Chem. 2019;11(10):1225–36. https://doi.org/10.4155/fmc-2018-0417.

    Article  CAS  PubMed  Google Scholar 

  175. Munagala R, et al. Bovine milk-derived exosomes for drug delivery. Cancer Lett. 2016;371(1):48–61. https://doi.org/10.1016/j.canlet.2015.10.020.

    Article  CAS  PubMed  Google Scholar 

  176. Kalani A, et al. Curcumin-loaded embryonic stem cell exosomes restored neurovascular unit following ischemia-reperfusion injury. Int J Biochem Cell Biol. 2016;79:360–9. https://doi.org/10.1016/j.biocel.2016.09.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Zhang D, et al. Enrichment of selective miRNAs in exosomes and delivery of exosomal miRNAs in vitro and in vivo. Am J Physiol Lung Cell Mol Physiol. 2017;312(1):L110–21. https://doi.org/10.1152/ajplung.00423.2016.

    Article  PubMed  Google Scholar 

  178. Izco M, et al. Systemic exosomal delivery of shRNA minicircles prevents Parkinsonian pathology. Mol Ther. 2019;27(12):2111–22. https://doi.org/10.1016/j.ymthe.2019.08.010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Hung ME, Leonard JN. Stabilization of exosome-targeting peptides via engineered glycosylation. J Biol Chem. 2015;290(13):8166–72. https://doi.org/10.1074/jbc.M114.621383.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors acknowledge support from Tarbiat Modares University and Shahid Beheshti University of Medical Sciences.

Author information

Author notes

  1. Fatemeh Bagheri, Masako Harada, Kaveh Baghaei share senior authorship on this work.

Authors and Affiliations

  1. Department of Biotechnology, Faculty of Chemical Engineering, Tarbiat Modares University, Tehran, Iran

    Amir Hossein Mohammadi & Fatemeh Bagheri

  2. Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Zeinab Ghazvinian

  3. Institute for Quantitative Health Science and Engineering (IQ), Michigan State University, East Lansing, MI, USA

    Masako Harada

  4. Department of Biomedical Engineering, Michigan State University, East Lansing, MI, USA

    Masako Harada

  5. Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Kaveh Baghaei

  6. Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Kaveh Baghaei

Authors
  1. Amir Hossein Mohammadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zeinab Ghazvinian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fatemeh Bagheri
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masako Harada
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kaveh Baghaei
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Fatemeh Bagheri, Masako Harada or Kaveh Baghaei.

Ethics declarations

Funding

This study was supported by the Iran National Science Foundation (INSF; Grant number 4003363) and Tarbiat Modares University.

Conflict of interest

Amir Hossein Mohammadi, Zeinab Ghazvinian, Fatemeh Bagheri, Masako Harada, and Kaveh Baghaei declare that they have no competing interests.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data and materials

Further information is available from the first author and corresponding authors upon request.

Code availability

Not applicable.

Author contributions

AHM and FB conceptualized the manuscript; AHM and ZG wrote the manuscript; AHM designed all figures of the manuscript; and FB, KB, and MH revised the final version of the manuscript and supervised the project. All authors read and approved the final version of the manuscript.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mohammadi, A.H., Ghazvinian, Z., Bagheri, F. et al. Modification of Extracellular Vesicle Surfaces: An Approach for Targeted Drug Delivery. BioDrugs 37, 353–374 (2023). https://doi.org/10.1007/s40259-023-00595-5

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40259-023-00595-5

Search

Navigation