Extracellular vesicles: The future of therapeutics and drug delivery systems
Md Jamir Uddin, Popat Mohite, Shubham Munde, Nitin Ade, Tosin Ayodeji Oladosu, Vijay R. Chidrawar, Ravish Patel, Sankha Bhattacharya, Himanshu Paliwal, Sudarshan Singh
Extracellular vesicles: The future of therapeutics and drug delivery systems
Extracellular vesicles (EVs) are nanometric size, a cell-derived drug delivery carrier composed of membranebound structures, release into the cellular medium and found in body fluids. EVs serve a dual purpose, acting as a means of disposing of redundant material and a method of communication between cells. Their natural origin, biocompatibility, protein, and nucleic acid composition boosts superior targeting capabilities. While strong safety profile, intrinsic pleiotropic therapeutic effects, ability to accommodate both lipophilic and hydrophilic agents, and pass through blood–brain barrier makes them exceptional nanocarrier. Several synthetic drug delivery methods have been fabricated and introduced to the market throughout the previous few decades. However, their inefficiency, cytotoxicity, and/or immunogenicity hinder their applications. Evidence demonstrates that EVs play a critical role in major physiological and pathological processes, such as cellular homeostasis, infection propagation, cancer progression, and cardiovascular diseases. Moreover, EVs offer a range of advantages over traditional synthetic carriers, thus paving the way for innovative drug delivery approaches. Although therapeutic applications as carrier is limited due to lack of scalable isolation techniques and efficient drug loading, EVs serve great potential as nanocarriers. The review summarizes and discuss recent progress and challenges associated with development of EVs as nanocarrier.
Drug delivery / Extracellular vesicles / Exosomes / Nanocarrier / Targeting / Up-scaling
[1] |
Borges FT, Reis LA, Schor N. Extracellular vesicles: structure, function, and potential clinical uses in renal diseases. Braz J Med Biol Res. 2013;46(10):824–830.
CrossRef
Google scholar
|
[2] |
Zaborowski MP, Balaj L, Breakefield XO, Lai CP. Extracellular vesicles: composition, biological relevance, and methods of study. Bioscience. 2015 Aug;65(8):783–797.
CrossRef
Google scholar
|
[3] |
Bebelman MP, Smit MJ, Pegtel DM, Baglio SR. Biogenesis and function of extracellular vesicles in cancer. Pharmacol Ther. 2018 Aug;188:1–11.
CrossRef
Google scholar
|
[4] |
Jeppesen DK, Fenix AM, Franklin JL, et al. Reassessment of exosome composition. Cell. 2019;177(2):428–445.e18.
CrossRef
Google scholar
|
[5] |
Yáñez-Mó M, Siljander PRM, Andreu Z, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4:27066.
CrossRef
Google scholar
|
[6] |
Palmisano G, Jensen SS, Le Bihan MC, et al. Characterization of membrane-shed microvesicles from cytokine-stimulated β-cells using proteomics strategies. Mol Cell Proteomics. 2012 Aug;11(8):230–243.
CrossRef
Google scholar
|
[7] |
Sonoda H, Yokota-Ikeda N, Oshikawa S, et al. Decreased abundance of urinary exosomal aquaporin-1 in renal ischemia-reperfusion injury. Am J Physiol Renal Physiol. 2009 Oct;297(4):F1006–F1016.
CrossRef
Google scholar
|
[8] |
Basso M, Bonetto V. Extracellular vesicles and a novel form of communication in the brain. Front Neurosci. 2016;10:127.
CrossRef
Google scholar
|
[9] |
Théry C, Witwer KW, Aikawa E, 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.
CrossRef
Google scholar
|
[10] |
Ali SY, Sajdera SW, Anderson HC. Isolation and characterization of calcifying matrix vesicles from epiphyseal cartilage. Proc Natl Acad Sci U S A. 1970 Nov;67(3):1513–1520.
CrossRef
Google scholar
|
[11] |
Ratajczak J, Miekus K, Kucia M, et al. Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia. 2006 May;20(5):847–856.
CrossRef
Google scholar
|
[12] |
Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007 Jun;9(6):654–659.
CrossRef
Google scholar
|
[13] |
Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature. 1998 Feb;391(6669):806–811.
CrossRef
Google scholar
|
[14] |
Borges FT, Reis LA, Schor N. Extracellular vesicles: structure, function, and potential clinical uses in renal diseases. Braz J Med Biol Res. 2013 Oct;46(10):824–830.
CrossRef
Google scholar
|
[15] |
Mardis ER. Next-generation DNA sequencing methods. Annu Rev Genomics Hum Genet. 2008;9:387–402.
CrossRef
Google scholar
|
[16] |
Das S, Ansel KM, Bitzer M, et al. The extracellular RNA communication consortium: establishing foundational knowledge and technologies for extracellular RNA research. Cell. 2019 Apr;177(2):231–242.
|
[17] |
Bianchi E, Doe B, Goulding D, Wright GJ. Juno is the egg Izumo receptor and is essential for mammalian fertilization. Nature. 2014 Apr;508(7497):483–487.
CrossRef
Google scholar
|
[18] |
Vagner T, Spinelli C, Minciacchi VR, et al. Large extracellular vesicles carry most of the tumour DNA circulating in prostate cancer patient plasma. J Extracell Vesicles. 2018;7(1):1505403.
CrossRef
Google scholar
|
[19] |
Shah R, Murthy V, Pacold M, et al. Extracellular RNAs are associated with insulin resistance and metabolic phenotypes. Diabetes Care. 2017 Apr;40(4):546–553.
CrossRef
Google scholar
|
[20] |
Capomaccio S, Vitulo N, Verini-Supplizi A, et al. RNA sequencing of the exercise transcriptome in equine athletes. PLoS One. 2013;8(12):e83504.
CrossRef
Google scholar
|
[21] |
Shah RV, Rong J, Larson MG, et al. Associations of circulating extracellular RNAs with myocardial remodeling and heart failure. JAMA Cardiol. 2018 Sep;3(9):871–876.
CrossRef
Google scholar
|
[22] |
Pua HH, Happ HC, Gray CJ, et al. Increased hematopoietic extracellular RNAs and vesicles in the lung during allergic airway responses. Cell Rep. 2019 Jan;26(4):933–944.e4.
CrossRef
Google scholar
|
[23] |
Shapiro IM, Landis WJ, Risbud MV. Matrix vesicles: are they anchored exosomes? Bone. 2015 Oct;79:29–36.
CrossRef
Google scholar
|
[24] |
Doyle L, Wang M. Overview of extracellular vesicles, their origin, composition, purpose, and methods for exosome isolation and analysis. Cells. 2019 Jul 15;8(7):727.
CrossRef
Google scholar
|
[25] |
Bebelman MP, Smit MJ, Pegtel DM, Baglio SR. Biogenesis and function of extracellular vesicles in cancer. Pharmacol Ther. 2018;188:1–11.
CrossRef
Google scholar
|
[26] |
Mathivanan S, Simpson RJ. ExoCarta: a compendium of exosomal proteins and RNA. Proteomics. 2009;9(21):4997–5000.
CrossRef
Google scholar
|
[27] |
Babst M, Katzmann DJ, Estepa-Sabal EJ, Meerloo T, Emr SD. ESCRT-III: an endosome-associated heterooligomeric protein complex required for MVB sorting. Dev Cell. 2002;3(2):271–282.
CrossRef
Google scholar
|
[28] |
Borges FT, Melo SA, Özdemir BC, et al. TGF-β1-Containing exosomes from injured epithelial cells activate fibroblasts to initiate tissue regenerative responses and fibrosis. J Am Soc Nephrol. 2013;24(3):385–392.
CrossRef
Google scholar
|
[29] |
Géminard C, de Gassart A, Blanc L, Vidal M. Degradation of AP2 during reticulocyte maturation enhances binding of hsc70 and Alix to a common site on TfR for sorting in exosomes. Traffic. 2004;5(3):181–193.
CrossRef
Google scholar
|
[30] |
Trajkovic K, Hsu C, Chiantia S, et al. Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science (1979). 2008;319(5867):1244–1247.
CrossRef
Google scholar
|
[31] |
Theos AC, Truschel ST, Tenza D, et al. A lumenal domain-dependent pathway for sorting to intralumenal vesicles of multivesicular endosomes involved in organelle morphogenesis. Dev Cell. 2006;10(3):343–354.
CrossRef
Google scholar
|
[32] |
Sinha A, Ignatchenko V, Ignatchenko A, Mejia-Guerrero S, Kislinger T. In-depth proteomic analyses of ovarian cancer cell line exosomes reveals differential enrichment of functional categories compared to the NCI 60 proteome. Biochem Biophys Res Commun. 2014;445(4):694–701.
CrossRef
Google scholar
|
[33] |
Tauro BJ, Greening DW, Mathias RA, Mathivanan S, Ji H, Simpson RJ. Two distinct populations of exosomes are released from LIM1863 colon carcinoma cell-derived organoids. Mol Cell Proteomics. 2013;12(3):587–598.
CrossRef
Google scholar
|
[34] |
Palmisano G, Jensen SS, Le Bihan MC, et al. Characterization of membrane-shed microvesicles from cytokine-stimulated β-cells using proteomics strategies. Mol Cell Proteomics. 2012;11(8):230–243.
CrossRef
Google scholar
|
[35] |
Bobrie A, Colombo M, Raposo G, Théry C. Exosome secretion: molecular mechanisms and roles in immune responses. Traffic. 2011;12(12):1659–1668.
CrossRef
Google scholar
|
[36] |
Fauré J, Lachenal G, Court M, et al. Exosomes are released by cultured cortical neurones. Mol Cell Neurosci. 2006;31(4):642–648.
CrossRef
Google scholar
|
[37] |
Fevrier B, Vilette D, Archer F, et al. Cells release prions in association with exosomes. Proc Natl Acad Sci U S A. 2004;101(26):9683–9688.
CrossRef
Google scholar
|
[38] |
Rashidi M, Bijari S, Khazaei AH, Shojaei-Ghahrizjani F, Rezakhani L. The role of milk-derived exosomes in the treatment of diseases. Front Genet. 2022 Oct 21:13.
CrossRef
Google scholar
|
[39] |
Chen J, Li P, Zhang T, et al. Review on strategies and technologies for exosome isolation and purification. Front Bioeng Biotechnol. 2022 Jan 5:9.
CrossRef
Google scholar
|
[40] |
Clancy JW, Schmidtmann M, D’Souza-Schorey C. The ins and outs of microvesicles. FASEB Bioadv. 2021 Jun 4;3(6):399–406.
CrossRef
Google scholar
|
[41] |
Zaborowski MP, Balaj L, Breakefield XO, Lai CP. Extracellular vesicles: composition, biological relevance, and methods of study. Bioscience. 2015;65(8):783–797.
CrossRef
Google scholar
|
[42] |
Cai H, Reinisch K, Ferro-Novick S. Coats, tethers, rabs, and SNAREs work together to mediate the intracellular destination of a transport vesicle. Dev Cell. 2007;12(5):671–682.
CrossRef
Google scholar
|
[43] |
Morelli AE, Larregina AT, Shufesky WJ, et al. Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells. Blood. 2004;104(10):3257–3266.
CrossRef
Google scholar
|
[44] |
Østergaard O, Nielsen CT, Iversen LV, Jacobsen S, Tanassi JT, Heegaard NHH. Quantitative proteome profiling of normal human circulating microparticles. J Proteome Res. 2012;11(4):2154–2163.
CrossRef
Google scholar
|
[45] |
Escola JM, Kleijmeer MJ, Stoorvogel W, Griffith JM, Yoshie O, Geuze HJ. Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes. J Biol Chem. 1998;273(32):20121–20127.
CrossRef
Google scholar
|
[46] |
Di Vizio D, Morello M, Dudley AC, et al. Large oncosomes in human prostate cancer tissues and in the circulation of mice with metastatic disease. Am J Pathol. 2012;181(5):1573–1584.
CrossRef
Google scholar
|
[47] |
Yáñez-Mó M, Siljander PRM, Andreu Z, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4(2015):1–60.
|
[48] |
Harding CV, Heuser JE, Stahl PD. Exosomes: looking back three decades and into the future. JCB (J Cell Biol). 2013;200(4):367–371.
CrossRef
Google scholar
|
[49] |
Rak J, Ph D. Microparticles in Cancer. 2010;1(212):888–906.
CrossRef
Google scholar
|
[50] |
Atkin-smith GK, Poon IKH. Disassembly of the dying : mechanisms and functions. Trends Cell Biol. 2016;xx:1–12.
|
[51] |
King KL, Cidlowski JA. Cell cycle regulation and apoptosis. Annu Rev Physiol. 1998;60:601–617.
CrossRef
Google scholar
|
[52] |
Wickman G, Julian L, Olson MF. How apoptotic cells aid in the removal of their own cold dead bodies. Cell Death Differ. 2012;19(5):735–742.
CrossRef
Google scholar
|
[53] |
Zarovni N, Corrado A, Guazzi P, et al. Integrated isolation and quantitative analysis of exosome shuttled proteins and nucleic acids using immunocapture approaches. Methods. 2015;87(1):46–58 (June).
CrossRef
Google scholar
|
[54] |
Bu H, He D, He X, Wang K. Exosomes: isolation, analysis, and applications in cancer detection and therapy. Chembiochem. 2019 Feb 15;20(4):451–461.
CrossRef
Google scholar
|
[55] |
Livshts MA, Khomyakova E, Evtushenko EG, et al. Isolation of exosomes by differential centrifugation: theoretical analysis of a commonly used protocol. Sci Rep. 2015;5(October):1–14.
CrossRef
Google scholar
|
[56] |
Doyle L, Wang M. Overview of extracellular vesicles, their origin, composition, purpose, and methods for exosome isolation and analysis. Cells. 2019 Jul 15;8(7):727.
CrossRef
Google scholar
|
[57] |
Zhang M, Jin K, Gao L, et al. Methods and technologies for exosome isolation and characterization. Small Methods. 2018;2(9):1–10.
CrossRef
Google scholar
|
[58] |
Li P, Kaslan M, Lee SH, Yao J, Gao Z. Progress in exosome isolation techniques. Theranostics. 2017;7(3):789–804.
CrossRef
Google scholar
|
[59] |
Kang D, Oh S, Ahn SM, Lee BH, Moon MH. Proteomic analysis of exosomes from human neural stem cells by flow field-flow fractionation and nanoflow liquid chromatography-tandem mass spectrometry. J Proteome Res. 2008 Aug;7(8):3475–3480.
CrossRef
Google scholar
|
[60] |
Conde-Vancells J, Rodriguez-Suarez E, Embade N, et al. Characterization and comprehensive proteome profiling of exosomes secreted by hepatocytes. J Proteome Res. 2008;7(12):5157–5166.
CrossRef
Google scholar
|
[61] |
Zeringer E, Barta T, Li M, Vlassov AV. Strategies for isolation of exosomes. Cold Spring Harb Protoc. 2015 Apr;2015(4):319–323.
CrossRef
Google scholar
|
[62] |
Lu Y, Ye L, Jian X, et al. Integrated microfluidic system for isolating exosome and analyzing protein marker PD-L1. Biosens Bioelectron. 2022 May;204:113879.
CrossRef
Google scholar
|
[63] |
Gao J, Li A, Hu J, Feng L, Liu L, Shen Z. Recent developments in isolating methods for exosomes. Front Bioeng Biotechnol. 2023 Jan 13:10.
CrossRef
Google scholar
|
[64] |
Alzhrani GN, Alanazi ST, Alsharif SY, et al. Exosomes: isolation, characterization, and biomedical applications. Cell Biol Int. 2021 Sep 11;45(9):1807–1831.
CrossRef
Google scholar
|
[65] |
Colombo M, Moita C, van Niel G, et al. Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. J Cell Sci. 2013 Dec;126(Pt 24):5553–5565.
|
[66] |
Crescitelli R, Lässer C, Jang SC, et al. Subpopulations of extracellular vesicles from human metastatic melanoma tissue identified by quantitative proteomics after optimized isolation. J Extracell Vesicles. 2020;9(1):1722433.
CrossRef
Google scholar
|
[67] |
Heyes DJ, Hardman SJO, Pedersen MN, et al. Light-induced structural changes in a full-length cyanobacterial phytochrome probed by time-resolved X-ray scattering. Commun Biol. 2019;2:1.
CrossRef
Google scholar
|
[68] |
Hinger SA, Cha DJ, Franklin JL, et al. Diverse long RNAs are differentially sorted into extracellular vesicles secreted by colorectal cancer cells. Cell Rep. 2018 Oct;25(3):715–725.e4.
CrossRef
Google scholar
|
[69] |
Stanton BA. Extracellular vesicles and host-pathogen interactions: a review of interkingdom signaling by small noncoding RNA. Genes. 2021 Jun;12(7).
CrossRef
Google scholar
|
[70] |
O’Brien K, Breyne K, Ughetto S, Laurent LC, Breakefield XO. RNA delivery by extracellular vesicles in mammalian cells and its applications. Nat Rev Mol Cell Biol. 2020 Oct;21(10):585–606.
CrossRef
Google scholar
|
[71] |
Mo CF, Wu FC, Tai KY, et al. Loss of non-coding RNA expression from the DLK1-DIO3 imprinted locus correlates with reduced neural differentiation potential in human embryonic stem cell lines. Stem Cell Res Ther. 2015 Jan;6(1):1.
CrossRef
Google scholar
|
[72] |
Kalra H, Simpson RJ, Ji H, et al. Vesiclepedia: a compendium for extracellular vesicles with continuous community annotation. PLoS Biol. 2012;10(12):e1001450.
CrossRef
Google scholar
|
[73] |
Mathivanan S, Simpson RJ. ExoCarta: a compendium of exosomal proteins and RNA. Proteomics. 2009 Nov;9(21):4997–5000.
CrossRef
Google scholar
|
[74] |
Murillo OD, Thistlethwaite W, Rozowsky J, et al. exRNA atlas analysis reveals distinct extracellular RNA cargo types and their carriers present across human biofluids. Cell. 2019 Apr;177(2):463–477.e15.
CrossRef
Google scholar
|
[75] |
Lai H, Li Y, Zhang H, et al. exoRBase 2.0: an atlas of mRNA, lncRNA and circRNA in extracellular vesicles from human biofluids. Nucleic Acids Res. 2022 Jan;50(D1): D118–D128.
CrossRef
Google scholar
|
[76] |
Burtenshaw D, Regan B, Owen K, et al. Exosomal composition, biogenesis and profiling using point-of-care diagnostics—implications for cardiovascular disease. Front Cell Dev Biol. 2022 Jun 1:10.
CrossRef
Google scholar
|
[77] |
McGough IJ, Vincent JP. Exosomes in developmental signalling. Development. 2016 Jul 15;143(14):2482–2493.
CrossRef
Google scholar
|
[78] |
Xie Y, Guan Q, Guo J, Chen Y, Yin Y, Han X. Hydrogels for exosome delivery in biomedical applications. Gels. 2022 May 24;8(6):328.
CrossRef
Google scholar
|
[79] |
Rech J, Getinger-Panek A, Gałka S, Bednarek I. Origin and composition of exosomes as crucial factors in designing drug delivery systems. Appl Sci. 2022 Nov 30;12(23):12259.
CrossRef
Google scholar
|
[80] |
Veziroglu EM, Mias GI. Characterizing extracellular vesicles and their diverse RNA contents. Front Genet. 2020 Jul 17:11.
CrossRef
Google scholar
|
[81] |
Kwok ZH, Wang C, Jin Y. Extracellular vesicle transportation and uptake by recipient cells: a critical process to regulate human diseases. Processes. 2021 Jan 31;9(2):273.
CrossRef
Google scholar
|
[82] |
Burtenshaw D, Regan B, Owen K, et al. Exosomal composition, biogenesis and profiling using point-of-care diagnostics—implications for cardiovascular disease. Front Cell Dev Biol. 2022 Jun 1:10.
CrossRef
Google scholar
|
[83] |
Kwok ZH, Wang C, Jin Y. Extracellular vesicle transportation and uptake by recipient cells: a critical process to regulate human diseases. Processes. 2021 Jan 31;9(2):273.
CrossRef
Google scholar
|
[84] |
Elsharkasy OM, Nordin JZ, Hagey DW, et al. Extracellular vesicles as drug delivery systems: why and how? Adv Drug Deliv Rev. 2020;159:332–343.
CrossRef
Google scholar
|
[85] |
Giordano C, La Camera G, Gelsomino L, et al. The biology of exosomes in breast cancer progression: dissemination, immune evasion and metastatic colonization. Cancers. 2020 Aug 5;12(8):2179.
CrossRef
Google scholar
|
[86] |
Kwok ZH, Wang C, Jin Y. Extracellular vesicle transportation and uptake by recipient cells: a critical process to regulate human diseases. Processes. 2021 Jan 31;9(2):273.
CrossRef
Google scholar
|
[87] |
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. 2019 Jan 2;21(1):9–17.
CrossRef
Google scholar
|
[88] |
Krylova SV, Feng D. The machinery of exosomes: biogenesis, release, and uptake. Int J Mol Sci. 2023 Jan 10;24(2):1337.
CrossRef
Google scholar
|
[89] |
Anand S, Samuel M, Kumar S, Mathivanan S. Ticket to a bubble ride: cargo sorting into exosomes and extracellular vesicles. Biochimica et Biophysica Acta (BBA) -Proteins and Proteomics. 2019 Dec;1867(12):140203.
CrossRef
Google scholar
|
[90] |
Ni K, Wang C, Carnino JM, Jin Y. The evolving role of caveolin-1: a critical regulator of extracellular vesicles. Med Sci. 2020 Nov 4;8(4):46.
CrossRef
Google scholar
|
[91] |
Wang W, Li M, Chen Z, et al. Biogenesis and function of extracellular vesicles in pathophysiological processes of skeletal muscle atrophy. Biochem Pharmacol. 2022 Apr;198:114954.
CrossRef
Google scholar
|
[92] |
Kwok ZH, Wang C, Jin Y. Extracellular vesicle transportation and uptake by recipient cells: a critical process to regulate human diseases. Processes. 2021 Jan 31;9(2):273.
CrossRef
Google scholar
|
[93] |
Kooijmans SAA, de Jong OG, Schiffelers RM. Exploring interactions between extracellular vesicles and cells for innovative drug delivery system design. Adv Drug Deliv Rev. 2021 Jun;173:252–278.
CrossRef
Google scholar
|
[94] |
Zaborowski MP, Balaj L, Breakefield XO, Lai CP. Extracellular vesicles: composition, biological relevance, and methods of study. Bioscience. 2015 Aug 1;65(8):783–797.
CrossRef
Google scholar
|
[95] |
Borges FT, Reis LA, Schor N. Extracellular vesicles: structure, function, and potential clinical uses in renal diseases. Braz J Med Biol Res. 2013 Oct;46(10):824–830.
CrossRef
Google scholar
|
[96] |
O’Brien K, Breyne K, Ughetto S, Laurent LC, Breakefield XO. RNA delivery by extracellular vesicles in mammalian cells and its applications. Nat Rev Mol Cell Biol. 2020 Oct 26;21(10):585–606.
CrossRef
Google scholar
|
[97] |
Kumar A, Ahmad A, Vyawahare A, Khan R. Membrane trafficking and subcellular drug targeting pathways. Front Pharmacol. 2020 May 27:11.
CrossRef
Google scholar
|
[98] |
de Jong OG, Kooijmans SAA, Murphy DE, et al. Drug delivery with extracellular vesicles: from imagination to innovation. Acc Chem Res. 2019 Jul 16;52(7):1761–1770.
CrossRef
Google scholar
|
[99] |
Guo M, Wu F, Hu G, et al. Autologous tumor cell–derived microparticle-based targeted chemotherapy in lung cancer patients with malignant pleural effusion. Sci Transl Med. 2019 Jan 9;(474):11.
CrossRef
Google scholar
|
[100] |
Haney MJ, Klyachko NL, Zhao Y, et al. Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J Contr Release. 2015 Jun;207:18–30.
CrossRef
Google scholar
|
[101] |
Kim MS, Haney MJ, Zhao Y, et al. Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomedicine. 2016 Apr;12(3):655–664.
CrossRef
Google scholar
|
[102] |
Chen CC, Liu L, Ma F, et al. Elucidation of exosome migration across the blood-brain barrier model in vitro. Cell Mol Bioeng. 2016 Dec 7;9(4):509–529.
CrossRef
Google scholar
|
[103] |
Jang SC, Kim OY, Yoon CM, et al. Bioinspired exosome-mimetic nanovesicles for targeted delivery of chemotherapeutics to malignant tumors. ACS Nano. 2013 Sep 24;7(9):7698–7710.
CrossRef
Google scholar
|
[104] |
Lai RC, Arslan F, Lee MM, et al. Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res. 2010 May;4(3):214–222.
CrossRef
Google scholar
|
[105] |
Montaner-Tarbes S, Novell E, Tarancón V, et al. Targeted-pig trial on safety and immunogenicity of serum-derived extracellular vesicles enriched fractions obtained from Porcine Respiratory and Reproductive virus infections. Sci Rep. 2018 Nov 30;8(1):17487.
CrossRef
Google scholar
|
[106] |
O’Loughlin AJ, Mäger I, de Jong OG, et al. Functional delivery of lipid-conjugated siRNA by extracellular vesicles. Mol Ther. 2017 Jul;25(7):1580–1587.
CrossRef
Google scholar
|
[107] |
Pessina A, Bonomi A, Coccè V, et al. Mesenchymal stromal cells primed with paclitaxel provide a new approach for cancer therapy. PLoS One. 2011 Dec 20;6(12):e28321.
CrossRef
Google scholar
|
[108] |
Piffoux M, Silva AKA, 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. 2018 Jul 24;12(7):6830–6842.
CrossRef
Google scholar
|
[109] |
Lucero R, Zappulli V, Sammarco A, et al. Glioma-derived miRNA-containing extracellular vesicles induce angiogenesis by reprogramming brain endothelial cells. Cell Rep. 2020 Feb;30(7):2065–2074.e4.
CrossRef
Google scholar
|
[110] |
Strzelec M, Detka J, Mieszczak P, Sobocińska MK, Majka M. Immunomodulation—a general review of the current state-of-the-art and new therapeutic strategies for targeting the immune system. Front Immunol. 2023 Mar 9:14.
CrossRef
Google scholar
|
[111] |
Jung I, Shin S, Baek MC, Yea K. Modification of immune cell-derived exosomes for enhanced cancer immunotherapy: current advances and therapeutic applications. Exp Mol Med. 2024 Jan 4;56(1):19–31.
CrossRef
Google scholar
|
[112] |
Ma Z, Xiang X, Li S, et al. Targeting hypoxia-inducible factor-1, for cancer treatment: recent advances in developing small-molecule inhibitors from natural compounds. Semin Cancer Biol. 2022 May;80:379–390.
CrossRef
Google scholar
|
[113] |
Huang M, Lei Y, Zhong Y, et al. New insights into the regulatory roles of extracellular vesicles in tumor angiogenesis and their clinical implications. Front Cell Dev Biol. 2021 Dec 13:9.
CrossRef
Google scholar
|
[114] |
Jia Y, Fu H. Association between innovative dockless bicycle sharing programs and adopting cycling in commuting and non-commuting trips. Transport Res Part A Policy Pract. 2019 Mar;121:12–21.
CrossRef
Google scholar
|
[115] |
Mashouri L, Yousefi H, Aref AR, mohammad Ahadi A, Molaei F, Alahari SK. Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance. Mol Cancer. 2019 Dec 2;18(1):75.
CrossRef
Google scholar
|
[116] |
Zhai M, Zhu Y, Yang M, Mao C. Human mesenchymal stem cell derived exosomes enhance cell-free bone regeneration by altering their miRNAs profiles. Adv Sci. 2020 Oct 7;7(19):2001334.
CrossRef
Google scholar
|
[117] |
Yang Z, Li Y, Wang Z. Recent advances in the application of mesenchymal stem cell-derived exosomes for cardiovascular and neurodegenerative disease therapies. Pharmaceutics. 2022 Mar 11;14(3):618.
CrossRef
Google scholar
|
[118] |
Aljuhani A, Albalawi O, Albalawi R, et al. Exosomes in COVID-19 infection: focus on role in diagnosis, pathogenesis, immunity, and clinical trials. Cell Biol Int. 2023 Jun 19;47(6):1049–1067.
CrossRef
Google scholar
|
[119] |
Wang Z, Popowski KD, Zhu D, et al. Exosomes decorated with a recombinant SARS-CoV-2 receptor-binding domain as an inhalable COVID-19 vaccine. Nat Biomed Eng. 2022 Jul 4;6(7):791–805.
CrossRef
Google scholar
|
[120] |
Chen Q, Chen J, Liu YN, Qi SH, Huang LY. Exosome-based drug delivery systems for the treatment of diabetes and its complications: current opinion. Extracell Vesicles Circ Nucl Acids. 2023;4(3):502–517.
CrossRef
Google scholar
|
[121] |
Sun Y, Tao Q, Wu X, Zhang L, Liu Q, Wang L. The utility of exosomes in diagnosis and therapy of diabetes mellitus and associated complications. Front Endocrinol. 2021 Oct 26:12.
CrossRef
Google scholar
|
[122] |
Yeo RWY, Lai RC, Zhang B, et al. Mesenchymal stem cell: an efficient mass producer of exosomes for drug delivery. Adv Drug Deliv Rev. 2013 Mar;65(3):336–341.
CrossRef
Google scholar
|
[123] |
Zhang Q, Zhang H, Ning T, et al. ≤p>Exosome-Delivered c-met siRNA could reverse chemoresistance to cisplatin in gastric cancer</p>. Int J Nanomed. 2020 Apr;15:2323–2335.
CrossRef
Google scholar
|
[124] |
Xiao Y, Zhong J, Zhong B, et al. Exosomes as potential sources of biomarkers in colorectal cancer. Cancer Lett. 2020 Apr;476:13–22.
CrossRef
Google scholar
|
[125] |
Piancone F, La Rosa F, Marventano I, Saresella M, Clerici M. The role of the inflammasome in neurodegenerative diseases. Molecules. 2021 Feb 11;26(4):953.
CrossRef
Google scholar
|
[126] |
Yang Z, Li Y, Wang Z. Recent advances in the application of mesenchymal stem cell-derived exosomes for cardiovascular and neurodegenerative disease therapies. Pharmaceutics. 2022 Mar 11;14(3):618.
CrossRef
Google scholar
|
[127] |
Huang JH, Yin XM, Xu Y, et al. Systemic administration of exosomes released from mesenchymal stromal cells attenuates apoptosis, inflammation, and promotes angiogenesis after spinal cord injury in rats. J Neurotrauma. 2017 Dec 15;34(24):3388–3396.
CrossRef
Google scholar
|
[128] |
Xin H, Li Y, Cui Y, Yang JJ, Zhang ZG, Chopp M. Systemic administration of exosomes released from mesenchymal stromal cells promote functional recovery and neurovascular plasticity after stroke in rats. J Cerebr Blood Flow Metabol. 2013 Nov 21;33(11):1711–1715.
CrossRef
Google scholar
|
[129] |
Ciferri MC, Quarto R, Tasso R. Extracellular vesicles as biomarkers and therapeutic tools: from pre-clinical to clinical applications. Biology. 2021 Apr 23;10(5):359.
CrossRef
Google scholar
|
/
〈 | 〉 |