Abstract
Exosomes are nanoscale extracellular vesicles that encapsulate a diverse range of biomolecules such as nucleic acids, proteins, and lipids. They are involved in several biological processes and mediate intracellular communication. Recent reports that they exhibit unique traits in pathological conditions have generated significant interest in employing them as diagnostic and therapeutic tools. Particularly, their potential to serve as drug delivery vehicles for the treatment of cancer and other diseases has been explored in numerous studies. This manuscript reviews recent developments in the field and discusses important considerations for further refinement of this approach and realization of more effective exosome-based drug delivery systems.
Keywords: Extracellular vesicles, drug delivery, nanotechnology, targeted therapy, chemotherapy, nanocarriers.
Graphical Abstract
[1]
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.
[2]
Wolf, P. The nature and significance of platelet products in human plasma. Br. J. Haematol., 1967, 13(3), 269-288.
[3]
Thery, C.; Ostrowski, M.; Segura, E. Membrane vesicles as conveyors of immune responses. Nat. Rev. Immunol., 2009, 9(8), 581-593.
[4]
Pan, B.T.; Johnstone, R.M. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: Selective externalization of the receptor. Cell, 1983, 33(3), 967-978.
[5]
Harding, C.; Heuser, J.; Stahl, P. Endocytosis and intracellular processing of transferrin and colloidal gold-transferrin in rat reticulocytes: Demonstration of a pathway for receptor shedding. Eur. J. Cell Biol., 1984, 35(2), 256-263.
[6]
Raposo, G.; Nijman, H.W.; Stoorvogel, W.; Liejendekker, R.; Harding, C.V.; Melief, C.J.; Geuze, H.J. B lymphocytes secrete antigen-presenting vesicles. J. Exp. Med., 1996, 183(3), 1161-1172.
[7]
Valadi, H.; Ekström, K.; Bossios, A.; Sjöstrand, M.; Lee, J.J.; Lötvall, J.O. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol., 2007, 9, 654-659.
[8]
Chaput, N.; Théry, C. Exosomes: Immune properties and potential clinical implementations. Semin. Immunol., 2011, 33(5), 419-440.
[9]
Potolicchio, I.; Carven, G.J.; Xu, X.; Stipp, C.; Riese, R.J.; Stern, L.J.; Santambrogio, L. Proteomic analysis of microglia-derived exosomes: Metabolic role of the aminopeptidase CD13 in neuropeptide catabolism. J. Immunol., 2005, 175(4), 2237-2243.
[10]
Faure, J.; Lachenal, G.; Court, M.; Hirrlinger, J.; Chatellard-Causse, C.; Blot, B.; Grange, J.; Schoehn, G.; Goldberg, Y.; Boyer, V.; Kirchhoff, F.; Raposo, G.; Garin, J.; Sadoul, R. Exosomes are released by cultured cortical neurones. Mol. Cell. Neurosci., 2006, 31(4), 642-648.
[11]
Guescini, M.; Genedani, S.; Stocchi, V.; Agnati, L.F. Astrocytes and glioblastoma cells release exosomes carrying mtDNA. J. Neural Transm., 2010, 117(1), 1-4.
[12]
Kesimer, M.; Scull, M.; Brighton, B.; DeMaria, G.; Burns, K.; O’Neal, W.; Pickles, R.J.; Sheehan, J.K. Characterization of exosome-like vesicles released from human tracheobronchial ciliated epithelium: a possible role in innate defense. FASEB J., 2009, 23(6), 1858-1868.
[13]
Chavez-Munoz, C.; Morse, J.; Kilani, R.; Ghahary, A. Primary human keratinocytes externalize stratifin protein via exosomes. J. Cell. Biochem., 2008, 104(6), 2165-2173.
[14]
Zhang, H.G.; Liu, C.; Su, K.; Yu, S.; Zhang, L.; Zhang, S.; Wang, J.; Cao, X.; Grizzle, W.; Kimberly, R.P. A membrane form of TNF-alpha presented by exosomes delays T cell activation-induced cell death. J. Immunol., 2006, 176(12), 7385-7393.
[15]
Fevrier, B.; Vilette, D.; Archer, F.; Loew, D.; Faigle, W.; Vidal, M.; Laude, H.; Raposo, G. Cells release prions in association with exosomes. Proc. Natl. Acad. Sci. USA, 2004, 101(26), 9683-9688.
[16]
Trajkovic, K.; Hsu, C.; Chiantia, S.; Rajendran, L.; Wenzel, D.; Wieland, F.; Schwille, P.; Brugger, B.; Simons, M. Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science, 2008, 319(5867), 1244-1247.
[17]
Lai, R.C.; Arslan, F.; Lee, M.M.; Sze, N.S.; Choo, A.; Chen, T.S.; Salto-Tellez, M.; Timmers, L.; Lee, C.N.; El Oakley, R.M.; Pasterkamp, G.; de Kleijn, D.P.; Lim, S.K. Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res., 2010, 4(3), 214-222.
[18]
Timmers, L.; Lim, S.K.; Hoefer, I.E.; Arslan, F.; Lai, R.C.; van Oorschot, A.A.; Goumans, M.J.; Strijder, C.; Sze, S.K.; Choo, A.; Piek, J.J.; Doevendans, P.A.; Pasterkamp, G.; de Kleijn, D.P. Human mesenchymal stem cell-conditioned medium improves cardiac function following myocardial infarction. Stem Cell Res., 2011, 6(3), 206-214.
[19]
Al-Nedawi, K.; Meehan, B.; Micallef, J.; Lhotak, V.; May, L.; Guha, A.; Rak, J. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat. Cell Biol., 2008, 10(5), 619-624.
[20]
Skog, J.; Wurdinger, T.; van Rijn, S.; Meijer, D.; Gainche, L.; Sena-Esteves, M.; Curry, W.T.; Carter, R.S.; Krichevsky, A.M.; Breakefield, X.O. Glioblastoma microvesicles transport RNA and protein that promote tumor growth and provide diagnostic biomarkers. Nat. Cell Biol., 2008, 10(12), 1470-1476.
[22]
Kooijmans, S.A.A.; Vader, P.; van Dommelen, S.M.; van Solinge, W.W.; Schiffelers, R.M. Exosome mimetics: A novel class of drug delivery systems. Int. J. Nanomedicine, 2012, 7, 1525-1541.
[23]
Meel, R.; Krawczyk‐Durka, M.; Solinge, W.W.; Schiffelers, R.M. Toward routine detection of extracellular vesicles in clinical samples. Int. J. Lab. Hematol., 2014, 36(3), 244-253.
[24]
El Andaloussi, S.; Mäger, I.; Breakefield, X.O.; Wood, M.J.A. Extracellular vesicles: Biology and emerging therapeutic opportunities. Nat. Rev. Drug Discov., 2013, 12, 347-357.
[25]
van der Pol, E.; Boing, A.N.; Harrison, P.; Sturk, A.; Nieuwland, R. Classification, functions, and clinical relevance of extracellular vesicles. Pharmacol. Rev., 2012, 64(3), 676-705.
[26]
Akers, J.C.; Gonda, D.; Kim, R.; Carter, B.S.; Chen, C.C. Biogenesis of extracellular vesicles (EV): Exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J. Neurooncol., 2013, 113(1), 1-11.
[27]
Muralidharan-Chari, V.; Clancy, J.W.; Sedgwick, A.; D’Souza-Schorey, C. Microvesicles: Mediators of extracellular communication during cancer progression. J. Cell Sci., 2010, 123(Pt 10), 1603-1611.
[28]
Pilzer, D.; Gasser, O.; Moskovich, O.; Schifferli, J.A.; Fishelson, Z. Emission of membrane vesicles: Roles in complement resistance, immunity and cancer. Semin. Immunopathol., 2005, 27(3), 375-387.
[29]
Shedden, K.; Xie, X.T.; Chandaroy, P.; Chang, Y.T.; Rosania, G.R. Expulsion of small molecules in vesicles shed by cancer cells. Cancer Res., 2003, 63(15), 4331-4337.
[30]
Bucki, R.; Bachelot-Loza, C.; Zachowski, A.; Giraud, F.; Sulpice, J.C. Calcium induces phospholipid redistribution and microvesicle release in human erythrocyte membranes by independent pathways. Biochemistry, 1998, 37(44), 15383-15391.
[31]
Aharon, A.; Tamari, T.; Brenner, B. Monocyte-derived microparticles and exosomes induce procoagulant and apoptotic effects on endothelial cells. Thromb. Haemost., 2008, 100(5), 878-885.
[32]
Wiley, J.S.; Sluyter, R.; Gu, B.J.; Stokes, L.; Fuller, S.J. The human P2X7 receptor and its role in innate immunity. Tissue Antigens, 2011, 78(5), 321-332.
[33]
Thomas, L.M.; Salter, R.D. Activation of macrophages by P2X7-induced microvesicles from myeloid cells is mediated by phospholipids and is partially dependent on TLR4. J. Immunol., 2010, 185(6), 3740-3749.
[34]
Marleau, A.M.; Chen, C.S.; Joyce, J.A.; Tullis, R.H. Exosome removal as a therapeutic adjuvant in cancer. J. Transl. Med., 2012, 10, 134.
[35]
Jia, S.; Zocco, D.; Samuels, M.L.; Chou, M.F.; Chammas, R.; Skog, J.; Zarovni, N.; Momen-Heravi, F.; Kuo, W.P. Emerging technologies in extracellular vesicle-based molecular diagnostics. Expert Rev. Mol. Diagn., 2014, 14(3), 307-321.
[36]
Vlassov, A.V.; Magdaleno, S.; Setterquist, R.; Conrad, R. Exosomes: Current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim. Biophys. Acta, 2012, 1820(7), 940-948.
[37]
Gatti, S.; Bruno, S.; Deregibus, M.C.; Sordi, A.; Cantaluppi, V.; Tetta, C.; Camussi, G. Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury. Nephrol. Dial. Transplant., 2011, 26(5), 1474-1483.
[38]
Del Conde, I.; Shrimpton, C.N.; Thiagarajan, P.; Lopez, J.A. Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. Blood, 2005, 106(5), 1604-1611.
[39]
Mack, M.; Kleinschmidt, A.; Bruhl, H.; Klier, C.; Nelson, P.J.; Cihak, J.; Plachy, J.; Stangassinger, M.; Erfle, V.; Schlondorff, D. Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: A mechanism for cellular human immunodeficiency virus 1 infection. Nat. Med., 2000, 6(7), 769-775.
[40]
Bellingham, S.A.; Guo, B.B.; Coleman, B.M.; Hill, A.F. Exosomes: Vehicles for the transfer of toxic proteins associated with neurodegenerative diseases? Front. Physiol., 2012, 3, 124.
[41]
Emmanouilidou, E.; Melachroinou, K.; Roumeliotis, T.; Garbis, S.D.; Ntzouni, M.; Margaritis, L.H.; Stefanis, L.; Vekrellis, K. Cell-produced alpha-synuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival. J. Neurosci., 2010, 30(20), 6838-6851.
[42]
Vella, L.J.; Sharples, R.A.; Lawson, V.A.; Masters, C.L.; Cappai, R.; Hill, A.F. Packaging of prions into exosomes is associated with a novel pathway of PrP processing. J. Pathol., 2007, 211(5), 582-590.
[43]
Camussi, G.; Deregibus, M-C.; Bruno, S.; Grange, C.; Fonsato, V.; Tetta, C. Exosome/microvesicle-mediated epigenetic reprogramming of cells. Am. J. Cancer Res., 2011, 1(1), 98-110.
[44]
Rak, J.; Guha, A. Extracellular vesicles--vehicles that spread cancer genes. BioEssays, 2012, 34(6), 489-497.
[45]
Cho, J.A.; Park, H.; Lim, E.H.; Kim, K.H.; Choi, J.S.; Lee, J.H.; Shin, J.W.; Lee, K.W. Exosomes from ovarian cancer cells induce adipose tissue-derived mesenchymal stem cells to acquire the physical and functional characteristics of tumor-supporting myofibroblasts. Gynecol. Oncol., 2011, 123(2), 379-386.
[46]
Wahlgren, J.; De, L.K.T.; Brisslert, M.; Vaziri Sani, F.; Telemo, E.; Sunnerhagen, P.; Valadi, H. Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes. Nucleic Acids Res., 2012, 40(17) e130
[47]
Alvarez-Erviti, L.; Seow, Y.; Yin, H.; Betts, C.; Lakhal, S.; Wood, M.J.A. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat. Biotechnol., 2011, 29, 341-345.
[48]
Zhuang, X.; Xiang, X.; Grizzle, W.; Sun, D.; Zhang, S.; Axtell, R.C.; Ju, S.; Mu, J.; Zhang, L.; Steinman, L.; Miller, D.; Zhang, H-G. Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol. Ther., 2011, 19(10), 1769-1779.
[49]
Sun, D.; Zhuang, X.; Xiang, X.; Liu, Y.; Zhang, S.; Liu, C.; Barnes, S.; Grizzle, W.; Miller, D.; Zhang, H-G. A novel nanoparticle drug delivery system: The anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes. Mol. Ther., 2010, 18(9), 1606-1614.
[50]
Takahashi, Y.; Nishikawa, M.; Shinotsuka, H.; Matsui, Y.; Ohara, S.; Imai, T.; Takakura, Y. Visualization and in vivo tracking of the exosomes of murine melanoma B16-BL6 cells in mice after intravenous injection. J. Biotechnol., 2013, 165(2), 77-84.
[51]
Hood, J.L.; Scott, M.J.; Wickline, S.A. Maximizing exosome colloidal stability following electroporation. Anal. Biochem., 2014, 448, 41-49.
[52]
Lee, Y.S.; Kim, S.H.; Cho, J.A.; Kim, C.W. Introduction of the CIITA gene into tumor cells produces exosomes with enhanced anti-tumor effects. Exp. Mol. Med., 2011, 43, 281-290.
[53]
Zitvogel, L.; Regnault, A.; Lozier, A.; Wolfers, J.; Flament, C.; Tenza, D.; Ricciardi-Castagnoli, P.; Raposo, G.; Amigorena, S. Eradication of established murine tumors using a novel cell-free vaccine: Dendritic cell derived exosomes. Nat. Med., 1998, 4, 594-600.
[54]
Tian, Y.; Li, S.; Song, J.; Ji, T.; Zhu, M.; Anderson, G.J.; Wei, J.; Nie, G. A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Biomaterials, 2014, 35(7), 2383-2390.
[55]
Viaud, S.; Théry, C.; Ploix, S.; Tursz, T.; Lapierre, V.; Lantz, O.; Zitvogel, L.; Chaput, N. Dendritic cell-derived exosomes for cancer immunotherapy: What’s next? Cancer Res., 2010, 70(4), 1281-1285.
[56]
Xin, H.; Li, Y.; Buller, B.; Katakowski, M.; Zhang, Y.; Wang, X.; Shang, X.; Zhang, Zheng. G.; Chopp, M. Exosome‐mediated transfer of miR‐133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth. Stem Cells, 2012, 30(7), 1556-1564.
[57]
Munoz, J.L.; Bliss, S.A.; Greco, S.J.; Ramkissoon, S.H.; Ligon, K.L.; Rameshwar, P. Delivery of functional anti-miR-9 by mesenchymal stem cell-derived exosomes to glioblastoma multiforme cells conferred chemosensitivity. Mol. Ther. Nucleic Acids, 2013, 2 e126
[58]
Katakowski, M.; Buller, B.; Zheng, X.; Lu, Y.; Rogers, T.; Osobamiro, O.; Shu, W.; Jiang, F.; Chopp, M. Exosomes from marrow stromal cells expressing miR-146b inhibit glioma growth. Cancer Lett., 2013, 335(1), 201-204.
[59]
Pascucci, L.; Coccè, V.; Bonomi, A.; Ami, D.; Ceccarelli, P.; Ciusani, E.; Viganò, L.; Locatelli, A.; Sisto, F.; Doglia, S.M.; Parati, E.; Bernardo, M.E.; Muraca, M.; Alessandri, G.; Bondiolotti, G.; Pessina, A. Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit in vitro tumor growth: A new approach for drug delivery. J. Control. Release, 2014, 192, 262-270.
[60]
Lim, P.K.; Bliss, S.A.; Patel, S.A.; Taborga, M.; Dave, M.A.; Gregory, L.A.; Greco, S.J.; Bryan, M.; Patel, P.S.; Rameshwar, P. Gap junction-mediated import of microRNA from bone marrow stromal cells can elicit cell cycle quiescence in breast cancer cells. Cancer Res., 2011, 71(5), 1550-1560.
[61]
Johnsen, K.B.; Gudbergsson, J.M.; Skov, M.N.; Pilgaard, L.; Moos, T.; Duroux, M. A comprehensive overview of exosomes as drug delivery vehicles - endogenous nanocarriers for targeted cancer therapy. Biochim. Biophys. Acta, 2014, 1846(1), 75-87.
[62]
Roccaro, A.M.; Sacco, A.; Maiso, P.; Azab, A.K.; Tai, Y-T.; Reagan, M.; Azab, F.; Flores, L.M.; Campigotto, F.; Weller, E.; Anderson, K.C.; Scadden, D.T.; Ghobrial, I.M. BM mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression. J. Clin. Investig., 2013, 123(4), 1542-1555.
[63]
Cho, J.A.; Park, H.; Lim, E.H.; Lee, K.W. Exosomes from breast cancer cells can convert adipose tissue-derived mesenchymal stem cells into myofibroblast-like cells. Int. J. Oncol., 2012, 40(1), 130-138.
[64]
Zhu, W.; Huang, L.; Li, Y.; Zhang, X.; Gu, J.; Yan, Y.; Xu, X.; Wang, M.; Qian, H.; Xu, W. Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo. Cancer Lett., 2012, 315(1), 28-37.
[65]
Peterson, M.F.; Otoc, N.; Sethi, J.K.; Gupta, A.; Antes, T.J. Integrated systems for exosome investigation. Methods, 2015, 87, 31-45.
[66]
Wan, Y.; Cheng, G.; Liu, X.; Hao, S-J.; Nisic, M.; Zhu, C-D.; Xia, Y-Q.; Li, W-Q.; Wang, Z-G.; Zhang, W-L.; Rice, S.J.; Sebastian, A.; Albert, I.; Belani, C.P.; Zheng, S-Y. Rapid magnetic isolation of extracellular vesicles via lipid-based nanoprobes. Nat. Biomed. Eng., 2017, 1, pii: 0058.
[67]
Dolatmoradi, A.; Mirtaheri, E.; El-Zahab, B. Thermo-acoustofluidic separation of vesicles based on cholesterol content. Lab Chip, 2017, 17(7), 1332-1339.
[68]
Gholizadeh, S.; Shehata Draz, M.; Zarghooni, M.; Sanati-Nezhad, A.; Ghavami, S.; Shafiee, H.; Akbari, M. Microfluidic approaches for isolation, detection, and characterization of extracellular vesicles: Current status and future directions. Biosens. Bioelectron., 2017, 91, 588-605.
[69]
Ziaei, P.; Geruntho, J.J.; Marin-Flores, O.G.; Berkman, C.E.; Grant Norton, M. Silica nanostructured platform for affinity capture of tumor-derived exosomes. J. Mater. Sci., 2017, 52(12), 6907-6916.
[70]
Xia, Y.; Liu, M.; Wang, L.; Yan, A.; He, W.; Chen, M.; Lan, J.; Xu, J.; Guan, L.; Chen, J. A visible and colorimetric aptasensor based on DNA-capped single-walled carbon nanotubes for detection of exosomes. Biosens. Bioelectron., 2017, 92, 8-15.
[71]
Ozpolat, B.; Sood, A.K.; Lopez-Berestein, G. Liposomal siRNA nanocarriers for cancer therapy. Adv. Drug Deliv. Rev., 2014, 66, 110-116.
[72]
Zhang, P.; An, K.; Duan, X.; Xu, H.; Li, F.; Xu, F. Recent advances in siRNA delivery for cancer therapy using smart nanocarriers. Drug Discov. Today, 2018, 23(4), 900-911.
[73]
El Andaloussi, S.; Lakhal, S.; Mäger, I.; Wood, M.J.A. Exosomes for targeted siRNA delivery across biological barriers. Adv. Drug Deliv. Rev., 2013, 65(3), 391-397.
[74]
Shtam, T.A.; Kovalev, R.A.; Varfolomeeva, E.Y.; Makarov, E.M.; Kil, Y.V.; Filatov, M.V. Exosomes are natural carriers of exogenous siRNA to human cells in vitro. Cell Commun. Signal., 2013, 11, 88.
[75]
Zhang, Y.; Liu, D.; Chen, X.; Li, J.; Li, L.; Bian, Z.; Sun, F.; Lu, J.; Yin, Y.; Cai, X.; Sun, Q.; Wang, K.; Ba, Y.; Wang, Q.; Wang, D.; Yang, J.; Liu, P.; Xu, T.; Yan, Q.; Zhang, J.; Zen, K.; Zhang, C-Y. Secreted monocytic miR-150 enhances targeted endothelial cell migration. Mol. Cell, 2010, 39(1), 133-144.
[76]
Bryniarski, K.; Ptak, W.; Jayakumar, A.; Pullmann, K.; Caplan, M.J.; Chairoungdua, A.; Lu, J.; Adams, B.D.; Sikora, E.; Nazimek, K.; Marquez, S.; Kleinstein, S.H.; Sangwung, P.; Iwakiri, Y.; Delgato, E.; Redegeld, F.; Blokhuis, B.R.; Wojcikowski, J.; Daniel, A.W.; Groot Kormelink, T.; Askenase, P.W. Antigen-specific, antibody-coated, exosome-like nanovesicles deliver suppressor T-cell microRNA-150 to effector T cells to inhibit contact sensitivity. J. Allergy Clin. Immunol., 2013, 132(1), 170-181.
[77]
Xin, H.; Li, Y.; Buller, B.; Katakowski, M.; Zhang, Y.; Wang, X.; Shang, X.; Zhang, Z.G.; Chopp, M. Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth. Stem Cells, 2012, 30(7), 1556-1564.
[78]
Chen, L.; Charrier, A.; Zhou, Y.; Chen, R.; Yu, B.; Agarwal, K.; Tsukamoto, H.; Lee, L.J.; Paulaitis Michael, E.; Brigstock David, R. Epigenetic regulation of connective tissue growth factor by microRNA‐214 delivery in exosomes from mouse or human hepatic stellate cells. Hepatology, 2013, 59(3), 1118-1129.
[79]
Alexander, M.; Hu, R.; Runtsch, M.C.; Kagele, D.A.; Mosbruger, T.L.; Tolmachova, T.; Seabra, M.C.; Round, J.L.; Ward, D.M.; O’Connell, R.M. Exosome-delivered microRNAs modulate the inflammatory response to endotoxin. Nat. Commun., 2015, 6, 7321.
[80]
Li, L.; Li, C.; Wang, S.; Wang, Z.; Jiang, J.; Wang, W.; Li, X.; Chen, J.; Liu, K.; Li, C.; Zhu, G. Exosomes derived from hypoxic oral squamous cell carcinoma cells deliver miR-21 to normoxic cells to elicit a prometastatic phenotype. Cancer Res., 2016, 76(7), 1770-1780.
[81]
Ohno, S-i.; Takanashi, M.; Sudo, K.; Ueda, S.; Ishikawa, A.; Matsuyama, N.; Fujita, K.; Mizutani, T.; Ohgi, T.; Ochiya, T.; Gotoh, N.; Kuroda, M. Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol. Ther., 2013, 21(1), 185-191.
[82]
Kosaka, N.; Iguchi, H.; Yoshioka, Y.; Hagiwara, K.; Takeshita, F.; Ochiya, T. Competitive interactions of cancer cells and normal cells via secretory microRNAs. J. Biol. Chem., 2012, 287(2), 1397-1405.
[83]
Lee, H.K.; Finniss, S.; Cazacu, S.; Bucris, E.; Ziv-Av, A.; Xiang, C.; Bobbitt, K.; Rempel, S.A.; Hasselbach, L.; Mikkelsen, T.; Slavin, S.; Brodie, C. Mesenchymal stem cells deliver synthetic microRNA mimics to glioma cells and glioma stem cells and inhibit their cell migration and self-renewal. Oncotarget, 2013, 4(2), 346-361.
[84]
Lou, G.; Song, X.; Yang, F.; Wu, S.; Wang, J.; Chen, Z.; Liu, Y. Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma. J. Hematol. Oncol., 2015, 8(1), 122.
[85]
Shimbo, K.; Miyaki, S.; Ishitobi, H.; Kato, Y.; Kubo, T.; Shimose, S.; Ochi, M. Exosome-formed synthetic microRNA-143 is transferred to osteosarcoma cells and inhibits their migration. Biochem. Biophys. Res. Commun., 2014, 445(2), 381-387.
[86]
Kanlikilicer, P.; Rashed, M.H.; Bayraktar, R.; Mitra, R.; Ivan, C.; Aslan, B.; Zhang, X.; Filant, J.; Silva, A.M.; Rodriguez-Aguayo, C.; Bayraktar, E.; Pichler, M.; Ozpolat, B.; Calin, G.A.; Sood, A.K.; Lopez-Berestein, G. Ubiquitous release of exosomal tumor suppressor miR-6126 from ovarian cancer cells. Cancer Res., 2016, 76(24), 7194-7207.
[87]
Hornung, V.; Bauernfeind, F.; Halle, A.; Samstad, E.O.; Kono, H.; Rock, K.L.; Fitzgerald, K.A.; Latz, E. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat. Immunol., 2008, 9(8), 847-856.
[88]
Jang, S.C.; Kim, O.Y.; Yoon, C.M.; Choi, D-S.; Roh, T-Y.; Park, J.; Nilsson, J.; Lötvall, J.; Kim, Y-K.; Gho, Y.S. Bioinspired exosome-mimetic nanovesicles for targeted delivery of chemotherapeutics to malignant tumors. ACS Nano, 2013, 7(9), 7698-7710.
[89]
Sathornsumetee, S.; Rich, J.N. New approaches to primary brain tumor treatment. Anticancer Drugs, 2006, 17(9), 1003-1016.
[90]
Yang, T.; Martin, P.; Fogarty, B.; Brown, A.; Schurman, K.; Phipps, R.; Yin, V.P.; Lockman, P.; Bai, S. Exosome delivered anticancer drugs across the blood-brain barrier for brain cancer therapy in Danio rerio. Pharm. Res., 2015, 32(6), 2003-2014.
[91]
Mizrak, A.; Bolukbasi, M.F.; Ozdener, G.B.; Brenner, G.J.; Madlener, S.; Erkan, E.P.; Ströbel, T.; Breakefield, X.O.; Saydam, O. Genetically engineered microvesicles carrying suicide mRNA/protein inhibit schwannoma tumor growth. Mol. Ther., 2013, 21(1), 101-108.
[92]
Munagala, R.; Aqil, F.; Jeyabalan, J.; Gupta, R.C. Bovine milk-derived exosomes for drug delivery. Cancer Lett., 2016, 371(1), 48-61.
[93]
Neumann, E.; Schaefer-Ridder, M.; Wang, Y.; Hofschneider, P.H. Gene transfer into mouse lyoma cells by electroporation in high electric fields. EMBO J., 1982, 1(7), 841-845.
[94]
Ha, D.; Yang, N.; Nadithe, V. Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: Current perspectives and future challenges. Acta Pharm. Sin. B, 2016, 6(4), 287-296.
[95]
Luan, X.; Sansanaphongpricha, K.; Myers, I.; Chen, H.; Yuan, H.; Sun, D. Engineering exosomes as refined biological nanoplatforms for drug delivery. Acta Pharmacol. Sin., 2017, 38(6), 754-763.
[96]
Kooijmans, S.A.A.; Stremersch, S.; Braeckmans, K.; de Smedt, S.C.; Hendrix, A.; Wood, M.J.A.; Schiffelers, R.M.; Raemdonck, K.; Vader, P. Electroporation-induced siRNA precipitation obscures the efficiency of siRNA loading into extracellular vesicles. J. Control. Release, 2013, 172(1), 229-238.
[97]
Syn, N.L.; Wang, L.; Chow, E.K.; Lim, C.T.; Goh, B.C. Exosomes in cancer nanomedicine and immunotherapy: prospects and challenges. Trends Biotechnol., 2017, 35(7), 665-676.
[98]
Rana, S.; Yue, S.; Stadel, D.; Zöller, M. Toward tailored exosomes: The exosomal tetraspanin web contributes to target cell selection. Int. J. Biochem. Cell Biol., 2012, 44(9), 1574-1584.
[99]
Ju, S.; Mu, J.; Dokland, T.; Zhuang, X.; Wang, Q.; Jiang, H.; Xiang, X.; Deng, Z.B.; Wang, B.; Zhang, L.; Roth, M.; Welti, R.; Mobley, J.; Jun, Y.; Miller, D.; Zhang, H.G. Grape exosome-like nanoparticles induce intestinal stem cells and protect mice from DSS-induced colitis. Mol. Ther., 2013, 21(7), 1345-1357.
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