Generic placeholder image

Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Review Article

The Potential of Milk-Derived Exosomes for Drug Delivery

Author(s): Shuyuan Li, Yue Tang* and Yushun Dou

Volume 18, Issue 6, 2021

Published on: 16 August, 2020

Page: [688 - 699] Pages: 12

DOI: 10.2174/1567201817666200817112503

Price: $65

Abstract

Background: Exosomes, one of the extracellular vesicles, are widely present in all biological fluids and play an important role in intercellular communication. Due to their hydrophobic lipid bilayer and aqueous hydrophilic core structure, they are considered a possible alternative to liposome drug delivery systems. Not only do they protect the cargo like liposomes during delivery, but they are also less toxic and better tolerated. However, due to the lack of sources and methods for obtaining enough exosomes, the therapeutic application of exosomes as drug carriers is limited.

Methods: A literature search was performed using the ScienceDirect and PubMed electronic databases to obtain information from published literature on milk exosomes related to drug delivery.

Results: Here, we briefly reviewed the current knowledge of exosomes, expounded the advantages of milk-derived exosomes over other delivery vectors, including higher yield, the oral delivery characteristic and additional therapeutic benefits. The purification and drug loading methods of milk exosomes, and the current application of milk exosomes were also introduced.

Conclusion: The emergence of milk-derived exosomes is expected to break through the limitations of exosomes as therapeutic carriers of drugs. We hope to raise awareness of the therapeutic potential of milk-derived exosomes as a new drug delivery system.

Keywords: Drug delivery system, extracellular vesicles, milk-derived exosomes, nanoparticles, oral delivery, liposomes.

Graphical Abstract
[1]
Johnstone, R.M.; Adam, M.; Hammond, J.R.; Orr, L.; Turbide, C. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J. Biol. Chem., 1987, 262(19), 9412-9420.
[PMID: 3597417]
[2]
EL, Andaloussi S.; Mäger, I.; Breakefield, X.O.; Wood, M.J. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat. Rev. Drug Discov., 2013, 12(5), 347-357.
[http://dx.doi.org/10.1038/nrd3978 ] [PMID: 23584393]
[3]
Batrakova, E.V.; Kim, M.S. Using exosomes, naturally-equipped nanocarriers, for drug delivery. J. Control. Release, 2015, 219, 396-405.
[http://dx.doi.org/10.1016/j.jconrel.2015.07.030 ] [PMID: 26241750]
[4]
Cline, A.M.; Radic, M.Z. Apoptosis, subcellular particles, and autoimmunity. Clin. Immunol., 2004, 112(2), 175-182.
[http://dx.doi.org/10.1016/j.clim.2004.02.017 ] [PMID: 15240161]
[5]
Shedden, K.; Xie, X.T.; Chandaroy, P.; Chang, Y.T.; Rosania, G.R. Expulsion of small molecules in vesicles shed by cancer cells: Association with gene expression and chemosensitivity profiles. Cancer Res., 2003, 63(15), 4331-4337.
[PMID: 12907600]
[6]
Shantsila, E.; Kamphuisen, P.W.; Lip, G.Y. Circulating microparticles in cardiovascular disease: implications for atherogenesis and atherothrombosis. J. Thromb. Haemost., 2010, 8(11), 2358-2368.
[http://dx.doi.org/10.1111/j.1538-7836.2010.04007.x ] [PMID: 20695980]
[7]
Vader, P.; Mol, E. A.; Pasterkamp, G.; Schiffelers, R. M. Extracellular vesicles for drug delivery. Adv. Drug Deliv. Rev., 2016, 106(Pt A), 148-156.
[http://dx.doi.org/10.1016/j.addr.2016.02.006]
[8]
Barile, L.; Vassalli, G. Exosomes: Therapy delivery tools and biomarkers of diseases. Pharmacol. Ther., 2017, 174, 63-78.
[http://dx.doi.org/10.1016/j.pharmthera.2017.02.020 ] [PMID: 28202367]
[9]
Schorey, J.S.; Bhatnagar, S. Exosome function: from tumor immunology to pathogen biology. Traffic, 2008, 9(6), 871-881.
[http://dx.doi.org/10.1111/j.1600-0854.2008.00734.x ] [PMID: 18331451]
[10]
Mathivanan, S.; Ji, H.; Simpson, R.J. Exosomes: extracellular organelles important in intercellular communication. J. Proteomics, 2010, 73(10), 1907-1920.
[http://dx.doi.org/10.1016/j.jprot.2010.06.006 ] [PMID: 20601276]
[11]
Xitong, D.; Xiaorong, Z. Targeted therapeutic delivery using engineered exosomes and its applications in cardiovascular diseases. Gene, 2016, 575(2 Pt 2), 377-384.
[http://dx.doi.org/10.1016/j.gene.2015.08.067 ] [PMID: 26341056]
[12]
Denzer, K.; Kleijmeer, M.J.; Heijnen, H.F.; Stoorvogel, W.; Geuze, H.J. Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. J. Cell Sci., 2000, 113(Pt 19), 3365-3374.
[PMID: 10984428]
[13]
Sahoo, S.; Losordo, D.W. Exosomes and cardiac repair after myocardial infarction. Circ. Res., 2014, 114(2), 333-344.
[http://dx.doi.org/10.1161/CIRCRESAHA.114.300639 ] [PMID: 24436429]
[14]
Nahand, J.S.; Mahjoubin-Tehran, M.; Moghoofei, M.; Pourhanifeh, M.H.; Mirzaei, H.R.; Asemi, Z.; Khatami, A.; Bokharaei-Salim, F.; Mirzaei, H.; Hamblin, M.R. Exosomal miRNAs: novel players in viral infection. Epigenomics, 2020, 12(4), 353-370.
[http://dx.doi.org/10.2217/epi-2019-0192 ] [PMID: 32093516]
[15]
Llorente, A.; Skotland, T.; Sylvänne, T.; Kauhanen, D.; Róg, T.; Orłowski, A.; Vattulainen, I.; Ekroos, K.; Sandvig, K. Molecular lipidomics of exosomes released by PC-3 prostate cancer cells. Biochim. Biophys. Acta, 2013, 1831(7), 1302-1309.
[http://dx.doi.org/10.1016/j.bbalip.2013.04.011 ] [PMID: 24046871]
[16]
Laulagnier, K.; Motta, C.; Hamdi, S.; Roy, S.; Fauvelle, F.; Pageaux, J.F.; Kobayashi, T.; Salles, J.P.; Perret, B.; Bonnerot, C.; Record, M. Mast cell- and dendritic cell-derived exosomes display a specific lipid composition and an unusual membrane organization. Biochem. J., 2004, 380(Pt 1), 161-171.
[http://dx.doi.org/10.1042/bj20031594 ] [PMID: 14965343]
[17]
Théry, C.; Boussac, M.; Véron, P.; Ricciardi-Castagnoli, P.; Raposo, G.; Garin, J.; Amigorena, S. Proteomic analysis of dendritic cell-derived exosomes: A secreted subcellular compartment distinct from apoptotic vesicles. J. Immunol., 2001, 166(12), 7309-7318.
[http://dx.doi.org/10.4049/jimmunol.166.12.7309]
[18]
Kowal, J.; Tkach, M.; Théry, C. Biogenesis and secretion of exosomes. Curr. Opin. Cell Biol., 2014, 29, 116-125.
[http://dx.doi.org/10.1016/j.ceb.2014.05.004 ] [PMID: 24959705]
[19]
Lötvall, J.; Hill, A.F.; Hochberg, F.; Buzás, E.I.; Di Vizio, D.; Gardiner, C.; Gho, Y.S.; Kurochkin, I.V.; Mathivanan, S.; Quesenberry, P.; Sahoo, S.; Tahara, H.; Wauben, M.H.; Witwer, K.W.; Théry, C. Minimal experimental requirements for definition of extracellular vesicles and their functions: A position statement from the international society for extracellular vesicles. J. Extracell. Vesicles, 2014, 3, 26913.
[http://dx.doi.org/10.3402/jev.v3.26913 ] [PMID: 25536934]
[20]
Théry, C.; Ostrowski, M.; Segura, E. Membrane vesicles as conveyors of immune responses. Nat. Rev. Immunol., 2009, 9(8), 581-593.
[http://dx.doi.org/10.1038/nri2567 ] [PMID: 19498381]
[21]
Yáñez-Mó, M.; Barreiro, O.; Gordon-Alonso, M.; Sala-Valdés, M.; Sánchez-Madrid, F. Tetraspanin-enriched microdomains: a functional unit in cell plasma membranes. Trends Cell Biol., 2009, 19(9), 434-446.
[http://dx.doi.org/10.1016/j.tcb.2009.06.004 ] [PMID: 19709882]
[22]
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.
[http://dx.doi.org/10.1084/jem.183.3.1161 ] [PMID: 8642258]
[23]
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(5), 594-600.
[http://dx.doi.org/10.1038/nm0598-594 ] [PMID: 9585234]
[24]
Lai, R.C.; Yeo, R.W.; Tan, K.H.; Lim, S.K. Exosomes for drug delivery - A novel application for the mesenchymal stem cell. Biotechnol. Adv., 2013, 31(5), 543-551.
[http://dx.doi.org/10.1016/j.biotechadv.2012.08.008 ] [PMID: 22959595]
[25]
Rabinowits, G.; Gerçel-Taylor, C.; Day, J.M.; Taylor, D.D.; Kloecker, G.H. Exosomal microRNA: A diagnostic marker for lung cancer. Clin. Lung Cancer, 2009, 10(1), 42-46.
[http://dx.doi.org/10.3816/CLC.2009.n.006 ] [PMID: 19289371]
[26]
Mack, M.; Kleinschmidt, A.; Brühl, H.; Klier, C.; Nelson, P.J.; Cihak, J.; Plachý, J.; Stangassinger, M.; Erfle, V.; Schlöndorff, 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.
[http://dx.doi.org/10.1038/77498 ] [PMID: 10888925]
[27]
Greco, V.; Hannus, M.; Eaton, S. Argosomes: A potential vehicle for the spread of morphogens through epithelia. Cell, 2001, 106(5), 633-645.
[http://dx.doi.org/10.1016/S0092-8674(01)00484-6 ] [PMID: 11551510]
[28]
Mirzaei, H.; Sahebkar, A.; Jaafari, M.R.; Goodarzi, M.; Mirzaei, H.R. Diagnostic and therapeutic potential of exosomes in cancer: The beginning of a new tale? J. Cell. Physiol., 2017, 232(12), 3251-3260.
[http://dx.doi.org/10.1002/jcp.25739 ] [PMID: 27966794]
[29]
Amiri, A.; Pourhanifeh, M.H.; Mirzaei, H.R.; Nahand, J.S.; Moghoofei, M.; Sahebnasagh, R.; Mirzaei, H.; Hamblin, M.R. Exosomes and Lung cancer: Roles in pathophysiology, diagnosis and therapeutic applications. Curr. Med. Chem., 2020, 28(2), 308-328.
[http://dx.doi.org/10.2174/0929867327666200204141952 ] [PMID: 32013817]
[30]
Mianehsaz, E.; Mirzaei, H.R.; Mahjoubin-Tehran, M.; Rezaee, A.; Sahebnasagh, R.; Pourhanifeh, M.H.; Mirzaei, H.; Hamblin, M.R. Mesenchymal stem cell-derived exosomes: A new therapeutic approach to osteoarthritis? Stem Cell Res. Ther., 2019, 10(1), 340.
[http://dx.doi.org/10.1186/s13287-019-1445-0 ] [PMID: 31753036]
[31]
Mohammadi, S.; Yousefi, F.; Shabaninejad, Z.; Movahedpour, A.; Mahjoubin Tehran, M.; Shafiee, A.; Moradizarmehri, S.; Hajighadimi, S.; Savardashtaki, A.; Mirzaei, H. Exosomes and cancer: From oncogenic roles to therapeutic applications. IUBMB Life, 2020, 72(4), 724-748.
[http://dx.doi.org/10.1002/iub.2182 ] [PMID: 31618516]
[32]
Zempleni, J.; Aguilar-Lozano, A.; Sadri, M.; Sukreet, S.; Manca, S.; Wu, D.; Zhou, F.; Mutai, E. Biological activities of extracellular vesicles and their cargos from bovine and human milk in humans and implications for infants. J. Nutr., 2017, 147(1), 3-10.
[http://dx.doi.org/10.3945/jn.116.238949 ] [PMID: 27852870]
[33]
Jiang, X.C.; Gao, J.Q. Exosomes as novel bio-carriers for gene and drug delivery. Int. J. Pharm., 2017, 521(1-2), 167-175.
[http://dx.doi.org/10.1016/j.ijpharm.2017.02.038 ] [PMID: 28216464]
[34]
Montecalvo, A.; Larregina, A.T.; Shufesky, W.J.; Stolz, D.B.; Sullivan, M.L.; Karlsson, J.M.; Baty, C.J.; Gibson, G.A.; Erdos, G.; Wang, Z.; Milosevic, J.; Tkacheva, O.A.; Divito, S.J.; Jordan, R.; Lyons-Weiler, J.; Watkins, S.C.; Morelli, A.E. Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood, 2012, 119(3), 756-766.
[http://dx.doi.org/10.1182/blood-2011-02-338004 ] [PMID: 22031862]
[35]
Hannafon, B.N.; Ding, W.Q. Intercellular communication by exosome-derived microRNAs in cancer. Int. J. Mol. Sci., 2013, 14(7), 14240-14269.
[http://dx.doi.org/10.3390/ijms140714240 ] [PMID: 23839094]
[36]
Yousefpour, P.; Chilkoti, A. Co-opting biology to deliver drugs. Biotechnol. Bioeng., 2014, 111(9), 1699-1716.
[http://dx.doi.org/10.1002/bit.25307 ] [PMID: 24916780]
[37]
Mulcahy, L.A.; Pink, R.C.; Carter, D.R. Routes and mechanisms of extracellular vesicle uptake. J. Extracell. Vesicles, 2014, 3, 24641.
[http://dx.doi.org/10.3402/jev.v3.24641 ] [PMID: 25143819]
[38]
Ridder, K.; Sevko, A.; Heide, J.; Dams, M.; Rupp, A.K.; Macas, J.; Starmann, J.; Tjwa, M.; Plate, K.H.; Sültmann, H.; Altevogt, P.; Umansky, V.; Momma, S. Extracellular vesicle-mediated transfer of functional RNA in the tumor microenvironment. OncoImmunology, 2015, 4(6)e1008371
[http://dx.doi.org/10.1080/2162402X.2015.1008371 ] [PMID: 26155418]
[39]
Zomer, A.; Maynard, C.; Verweij, F.J.; Kamermans, A.; Schäfer, R.; Beerling, E.; Schiffelers, R.M.; de Wit, E.; Berenguer, J.; Ellenbroek, S.I.J.; Wurdinger, T.; Pegtel, D.M.; van Rheenen, J. In Vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior. Cell, 2015, 161(5), 1046-1057.
[http://dx.doi.org/10.1016/j.cell.2015.04.042 ] [PMID: 26000481]
[40]
Alhasan, A.H.; Patel, P.C.; Choi, C.H.; Mirkin, C.A. Exosome encased spherical nucleic acid gold nanoparticle conjugates as potent microRNA regulation agents. Small, 2014, 10(1), 186-192.
[http://dx.doi.org/10.1002/smll.201302143 ] [PMID: 24106176]
[41]
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(4), 341-345.
[http://dx.doi.org/10.1038/nbt.1807 ] [PMID: 21423189]
[42]
Zhu, G.Y.; Lu, B.Y.; Zhang, T.X.; Zhang, T.; Zhang, C.L.; Li, Y.; Peng, Q. Antibiofilm effect of drug-free and cationic poly(D,L-lactide-co-glycolide) nanoparticles via nano-bacteria interactions. Nanomedicine (Lond.), 2018, 13(10), 1093-1106.
[http://dx.doi.org/10.2217/nnm-2017-0391 ] [PMID: 29873582]
[43]
Shao, X.R.; Wei, X.Q.; Zhang, S.; Fu, N.; Lin, Y.F.; Cai, X.X.; Peng, Q. Effects of micro-environmental pH of liposome on chemical stability of loaded drug. Nanoscale Res. Lett., 2017, 12(1), 504.
[http://dx.doi.org/10.1186/s11671-017-2256-9 ] [PMID: 28836126]
[44]
Liu, J.; Dong, J.; Zhang, T.; Peng, Q. Graphene-based nanomaterials and their potentials in advanced drug delivery and cancer therapy. J. Control. Release, 2018, 286, 64-73.
[http://dx.doi.org/10.1016/j.jconrel.2018.07.034 ] [PMID: 30031155]
[45]
Peng, Q.; Wei, X.Q.; Shao, X.R.; Zhang, T.; Zhang, S.; Fu, N.; Cai, X.X.; Zhang, Z.R.; Lin, Y.F. Nanocomplex based on biocompatible phospholipids and albumin for long-circulation applications. ACS Appl. Mater. Interfaces, 2014, 6(16), 13730-13737.
[http://dx.doi.org/10.1021/am503179a ] [PMID: 25058846]
[46]
Zhang, T.; Zhu, G.; Lu, B.; Peng, Q. Oral nano-delivery systems for colon targeting therapy. Pharm. Nanotechnol., 2017, 5(2), 83-94.
[http://dx.doi.org/10.2174/2211738505666170424122722 ] [PMID: 28440202]
[47]
Yao, Y.; Liao, W.; Yu, R.; Du, Y.; Zhang, T.; Peng, Q. Potentials of combining nanomaterials and stem cell therapy in myocardial repair. Nanomedicine (Lond.), 2018, 13(13), 1623-1638.
[http://dx.doi.org/10.2217/nnm-2018-0013 ] [PMID: 30028249]
[48]
Shao, X.R.; Wei, X.Q.; Song, X.; Hao, L.Y.; Cai, X.X.; Zhang, Z.R.; Peng, Q.; Lin, Y.F. Independent effect of polymeric nanoparticle zeta potential/surface charge, on their cytotoxicity and affinity to cells. Cell Prolif., 2015, 48(4), 465-474.
[http://dx.doi.org/10.1111/cpr.12192 ] [PMID: 26017818]
[49]
Ahn, J.; Cho, C.S.; Cho, S.W.; Kang, J.H.; Kim, S.Y.; Min, D.H.; Song, J.M.; Park, T.E.; Jeon, N.L. Investigation on vascular cytotoxicity and extravascular transport of cationic polymer nanoparticles using perfusable 3D microvessel model. Acta Biomater., 2018, 76, 154-163.
[http://dx.doi.org/10.1016/j.actbio.2018.05.041 ] [PMID: 29807185]
[50]
Peng, Q.; Zhang, S.; Yang, Q.; Zhang, T.; Wei, X.Q.; Jiang, L.; Zhang, C.L.; Chen, Q.M.; Zhang, Z.R.; Lin, Y.F. Preformed albumin corona, a protective coating for nanoparticles based drug delivery system. Biomaterials, 2013, 34(33), 8521-8530.
[http://dx.doi.org/10.1016/j.biomaterials.2013.07.102 ] [PMID: 23932500]
[51]
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.
[http://dx.doi.org/10.1016/j.apsb.2016.02.001 ] [PMID: 27471669]
[52]
Kooijmans, S.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.
[PMID: 22619510]
[53]
Kalra, H.; Adda, C.G.; Liem, M.; Ang, C.S.; Mechler, A.; Simpson, R.J.; Hulett, M.D.; Mathivanan, S. Comparative proteomics evaluation of plasma exosome isolation techniques and assessment of the stability of exosomes in normal human blood plasma. Proteomics, 2013, 13(22), 3354-3364.
[http://dx.doi.org/10.1002/pmic.201300282 ] [PMID: 24115447]
[54]
El Andaloussi, S.; Lakhal, S.; Mäger, I.; Wood, M.J. Exosomes for targeted siRNA delivery across biological barriers. Adv. Drug Deliv. Rev., 2013, 65(3), 391-397.
[http://dx.doi.org/10.1016/j.addr.2012.08.008 ] [PMID: 22921840]
[55]
Clayton, A.; Harris, C.L.; Court, J.; Mason, M.D.; Morgan, B.P. Antigen-presenting cell exosomes are protected from complement-mediated lysis by expression of CD55 and CD59. Eur. J. Immunol., 2003, 33(2), 522-531.
[http://dx.doi.org/10.1002/immu.200310028 ] [PMID: 12645951]
[56]
Müller, J.; Prozeller, D.; Ghazaryan, A.; Kokkinopoulou, M.; Mailänder, V.; Morsbach, S.; Landfester, K. Beyond the protein corona - lipids matter for biological response of nanocarriers. Acta Biomater., 2018, 71, 420-431.
[http://dx.doi.org/10.1016/j.actbio.2018.02.036 ] [PMID: 29524674]
[57]
Casals, E.; Pfaller, T.; Duschl, A.; Oostingh, G.J.; Puntes, V. Time evolution of the nanoparticle protein corona. ACS Nano, 2010, 4(7), 3623-3632.
[http://dx.doi.org/10.1021/nn901372t ] [PMID: 20553005]
[58]
Maiorano, G.; Sabella, S.; Sorce, B.; Brunetti, V.; Malvindi, M.A.; Cingolani, R.; Pompa, P.P. Effects of cell culture media on the dynamic formation of protein-nanoparticle complexes and influence on the cellular response. ACS Nano, 2010, 4(12), 7481-7491.
[http://dx.doi.org/10.1021/nn101557e ] [PMID: 21082814]
[59]
Liao, W.; Du, Y.; Zhang, C.; Pan, F.; Yao, Y.; Zhang, T.; Peng, Q. Exosomes: The next generation of endogenous nanomaterials for advanced drug delivery and therapy. Acta Biomater., 2019, 86, 1-14.
[http://dx.doi.org/10.1016/j.actbio.2018.12.045 ] [PMID: 30597259]
[60]
Dams, E.T.; Laverman, P.; Oyen, W.J.; Storm, G.; Scherphof, G.L.; van Der Meer, J.W.; Corstens, F.H.; Boerman, O.C. Accelerated blood clearance and altered biodistribution of repeated injections of sterically stabilized liposomes. J. Pharmacol. Exp. Ther., 2000, 292(3), 1071-1079.
[PMID: 10688625]
[61]
Ishida, T.; Maeda, R.; Ichihara, M.; Irimura, K.; Kiwada, H. Accelerated clearance of PEGylated liposomes in rats after repeated injections. J. Control. Release, 2003, 88(1), 35-42.
[http://dx.doi.org/10.1016/S0168-3659(02)00462-5 ] [PMID: 12586501]
[62]
Ishida, T.; Kashima, S.; Kiwada, H. The contribution of phagocytic activity of liver macrophages to the Accelerated Blood Clearance (ABC) phenomenon of PEGylated liposomes in rats. J. Control. Release, 2008, 126(2), 162-165.
[http://dx.doi.org/10.1016/j.jconrel.2007.11.009 ] [PMID: 18160170]
[63]
Sundar, S.; Jha, T.K.; Thakur, C.P.; Mishra, M.; Singh, V.P.; Buffels, R. Single-dose liposomal amphotericin B in the treatment of visceral leishmaniasis in India: A multicenter study. Clin. Infect. Dis., 2003, 37(6), 800-804.
[http://dx.doi.org/10.1086/377542 ] [PMID: 12955641]
[64]
Grant, G.J.; Barenholz, Y.; Bolotin, E.M.; Bansinath, M.; Turndorf, H.; Piskoun, B.; Davidson, E.M. A novel liposomal bupivacaine formulation to produce ultralong-acting analgesia. Anesthesiology, 2004, 101(1), 133-137.
[http://dx.doi.org/10.1097/00000542-200407000-00021 ] [PMID: 15220782]
[65]
Barenholz, Y. Doxil®-the first FDA-approved nano-drug: lessons learned. J. Control. Release, 2012, 160(2), 117-134.
[http://dx.doi.org/10.1016/j.jconrel.2012.03.020 ] [PMID: 22484195]
[66]
Munagala, R.; Aqil, F.; Jeyabalan, J.; Agrawal, A.K.; Mudd, A.M.; Kyakulaga, A.H.; Singh, I.P.; Vadhanam, M.V.; Gupta, R.C. Exosomal formulation of anthocyanidins against multiple cancer types. Cancer Lett., 2017, 393, 94-102.
[http://dx.doi.org/10.1016/j.canlet.2017.02.004 ] [PMID: 28202351]
[67]
Bamrungsap, S.; Zhao, Z.; Chen, T.; Wang, L.; Li, C.; Fu, T.; Tan, W. Nanotechnology in therapeutics: a focus on nanoparticles as a drug delivery system. Nanomedicine (Lond.), 2012, 7(8), 1253-1271.
[http://dx.doi.org/10.2217/nnm.12.87 ] [PMID: 22931450]
[68]
Lim, E.K.; Jang, E.; Lee, K.; Haam, S.; Huh, Y.M. Delivery of cancer therapeutics using nanotechnology. Pharmaceutics, 2013, 5(2), 294-317.
[http://dx.doi.org/10.3390/pharmaceutics5020294 ] [PMID: 24300452]
[69]
Smyth, T.J.; Redzic, J.S.; Graner, M.W.; Anchordoquy, T.J. Examination of the specificity of tumor cell derived exosomes with tumor cells in vitro. Biochim. Biophys. Acta, 2014, 1838(11), 2954-2965.
[http://dx.doi.org/10.1016/j.bbamem.2014.07.026 ] [PMID: 25102470]
[70]
Kamerkar, S.; LeBleu, V.S.; Sugimoto, H.; Yang, S.; Ruivo, C.F.; Melo, S.A.; Lee, J.J.; Kalluri, R. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature, 2017, 546(7659), 498-503.
[http://dx.doi.org/10.1038/nature22341 ] [PMID: 28607485]
[71]
Hu, Y-L.; Huang, B.; Zhang, T-Y.; Miao, P-H.; Tang, G-P.; Tabata, Y.; Gao, J-Q. Mesenchymal stem cells as a novel carrier for targeted delivery of gene in cancer therapy based on nonviral transfection. Mol. Pharm., 2012, 9(9), 2698-2709.
[http://dx.doi.org/10.1021/mp300254s ] [PMID: 22862421]
[72]
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.
[http://dx.doi.org/10.1016/j.jconrel.2014.07.042 ] [PMID: 25084218]
[73]
Mohammadi, M.; Jaafari, M.R.; Mirzaei, H.R.; Mirzaei, H. Mesenchymal stem cell: A new horizon in cancer gene therapy. Cancer Gene Ther., 2016, 23(9), 285-286.
[http://dx.doi.org/10.1038/cgt.2016.35 ] [PMID: 27650780]
[74]
Moradian Tehrani, R.; Verdi, J.; Noureddini, M.; Salehi, R.; Salarinia, R.; Mosalaei, M.; Simonian, M.; Alani, B.; Ghiasi, M.R.; Jaafari, M.R.; Mirzaei, H.R.; Mirzaei, H. Mesenchymal stem cells: A new platform for targeting suicide genes in cancer. J. Cell. Physiol., 2018, 233(5), 3831-3845.
[http://dx.doi.org/10.1002/jcp.26094 ] [PMID: 28703313]
[75]
Zhang, T.Y.; Huang, B.; Wu, H.B.; Wu, J.H.; Li, L.M.; Li, Y.X.; Hu, Y.L.; Han, M.; Shen, Y.Q.; Tabata, Y.; Gao, J.Q. Synergistic effects of co-administration of suicide gene expressing mesenchymal stem cells and prodrug-encapsulated liposome on aggressive lung melanoma metastases in mice. J. Control. Release, 2015, 209, 260-271.
[http://dx.doi.org/10.1016/j.jconrel.2015.05.007 ] [PMID: 25966361]
[76]
Hu, Y.L.; Fu, Y.H.; Tabata, Y.; Gao, J.Q. Mesenchymal stem cells: a promising targeted-delivery vehicle in cancer gene therapy. J. Control. Release, 2010, 147(2), 154-162.
[http://dx.doi.org/10.1016/j.jconrel.2010.05.015 ] [PMID: 20493219]
[77]
Rani, S.; Ryan, A.E.; Griffin, M.D.; Ritter, T. Mesenchymal stem cell-derived extracellular vesicles: Toward cell-free therapeutic applications. Mol. Ther., 2015, 23(5), 812-823.
[http://dx.doi.org/10.1038/mt.2015.44 ] [PMID: 25868399]
[78]
Farooqi, A.A.; Desai, N.N.; Qureshi, M.Z.; Librelotto, D.R.N.; Gasparri, M.L.; Bishayee, A.; Nabavi, S.M.; Curti, V.; Daglia, M. Exosome biogenesis, bioactivities and functions as new delivery systems of natural compounds. Biotechnol. Adv., 2018, 36(1), 328-334.
[http://dx.doi.org/10.1016/j.biotechadv.2017.12.010 ] [PMID: 29248680]
[79]
Wahlgren, J.; De, L. Karlson, 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
[http://dx.doi.org/10.1093/nar/gks463 ] [PMID: 22618874]
[80]
Ohno, S.; 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.
[http://dx.doi.org/10.1038/mt.2012.180 ] [PMID: 23032975]
[81]
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.
[http://dx.doi.org/10.1038/mt.2012.161 ] [PMID: 22910294]
[82]
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.
[http://dx.doi.org/10.1016/j.jbiotec.2013.03.013 ] [PMID: 23562828]
[83]
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(5), 281-290.
[http://dx.doi.org/10.3858/emm.2011.43.5.029 ] [PMID: 21464590]
[84]
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.
[http://dx.doi.org/10.1016/j.biomaterials.2013.11.083 ] [PMID: 24345736]
[85]
Hsu, D-H.; Paz, P.; Villaflor, G.; Rivas, A.; Mehta-Damani, A.; Angevin, E.; Zitvogel, L.; Le Pecq, J-B. Exosomes as a tumor vaccine: enhancing potency through direct loading of antigenic peptides. J. Immunother., 2003, 26(5), 440-450.
[http://dx.doi.org/10.1097/00002371-200309000-00007 ] [PMID: 12973033]
[86]
Yeo, R.W.; Lai, R.C.; Zhang, B.; Tan, S.S.; Yin, Y.; Teh, B.J.; Lim, S.K. Mesenchymal stem cell: an efficient mass producer of exosomes for drug delivery. Adv. Drug Deliv. Rev., 2013, 65(3), 336-341.
[http://dx.doi.org/10.1016/j.addr.2012.07.001 ] [PMID: 22780955]
[87]
Chen, T.S.; Arslan, F.; Yin, Y.; Tan, S.S.; Lai, R.C.; Choo, A.B.H.; Padmanabhan, J.; Lee, C.N.; de Kleijn, D.P.V.; Lim, S.K. Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs. J. Transl. Med., 2011, 9(1), 47.
[http://dx.doi.org/10.1186/1479-5876-9-47 ] [PMID: 21513579]
[88]
Arntz, O.J.; Pieters, B.C.H.; Oliveira, M.C.; Broeren, M.G.A.; Bennink, M.B.; de Vries, M.; van Lent, P.L.E.M.; Koenders, M.I.; van den Berg, W.B.; van der Kraan, P.M.; van de Loo, F.A.J. Oral administration of bovine milk derived extracellular vesicles attenuates arthritis in two mouse models. Mol. Nutr. Food Res., 2015, 59(9), 1701-1712.
[http://dx.doi.org/10.1002/mnfr.201500222 ] [PMID: 26047123]
[89]
Munagala, R.; Aqil, F.; Jeyabalan, J.; Gupta, R.C. Bovine milk-derived exosomes for drug delivery. Cancer Lett., 2016, 371(1), 48-61.
[http://dx.doi.org/10.1016/j.canlet.2015.10.020 ] [PMID: 26604130]
[90]
Rahman, M.J.; Regn, D.; Bashratyan, R.; Dai, Y.D. Exosomes Released by Islet-Derived Mesenchymal Stem Cells Trigger Autoimmune Responses in NOD Mice., 2014, 63(3), 1008-1020.
[91]
Sheng, H.; Hassanali, S.; Nugent, C.; Wen, L.; Hamilton-Williams, E.; Dias, P.; Dai, Y.D. Insulinoma-released exosomes or microparticles are immunostimulatory and can activate autoreactive T cells spontaneously developed in nonobese diabetic mice. J. Immunol., 2011, 187(4), 1591-1600.
[http://dx.doi.org/10.4049/jimmunol.1100231]
[92]
Mitchell, J.P.; Court, J.; Mason, M.D.; Tabi, Z.; Clayton, A. Increased exosome production from tumour cell cultures using the Integra CELLine Culture System. J. Immunol. Methods, 2008, 335(1-2), 98-105.
[http://dx.doi.org/10.1016/j.jim.2008.03.001 ] [PMID: 18423480]
[93]
Qi, J.; Zhou, Y.; Jiao, Z.; Wang, X.; Zhao, Y.; Li, Y.; Chen, H.; Yang, L.; Zhu, H.; Li, Y. Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth through hedgehog signaling pathway. Cell. Physiol. Biochem., 2017, 42(6), 2242-2254.
[http://dx.doi.org/10.1159/000479998 ] [PMID: 28817816]
[94]
Kordelas, L.; Rebmann, V.; Ludwig, A.K.; Radtke, S.; Ruesing, J.; Doeppner, T.R.; Epple, M.; Horn, P.A.; Beelen, D.W.; Giebel, B. MSC-derived exosomes: A novel tool to treat therapy-refractory graft-versus-host disease. Leukemia, 2014, 28(4), 970-973.
[http://dx.doi.org/10.1038/leu.2014.41 ] [PMID: 24445866]
[95]
Somiya, M.; Yoshioka, Y.; Ochiya, T. Biocompatibility of highly purified bovine milk-derived extracellular vesicles. J. Extracell. Vesicles, 2018, 7(1)1440132
[http://dx.doi.org/10.1080/20013078.2018.1440132 ] [PMID: 29511463]
[96]
Thery, C.; Amigorena, S.; Raposo, G.; Clayton, A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr. Protoc. Cell Biol., 2006.
[http://dx.doi.org/10.1002/0471143030.cb0322s30]
[97]
Simpson, R.J.; Mathivanan, S. Extracellular microvesicles: The need for internationally recognised nomenclature and stringent purification criteria. J. Proteomics Bioinform., 2012, 5, ii-ii.
[http://dx.doi.org/10.4172/jpb.10000e10]
[98]
Greening, D.W.; Xu, R.; Ji, H.; Tauro, B.J.; Simpson, R.J. A protocol for exosome isolation and characterization: evaluation of ultracentrifugation, density-gradient separation, and immunoaffinity capture methods. Methods Mol. Biol., 2015, 1295, 179-209.
[http://dx.doi.org/10.1007/978-1-4939-2550-6_15 ] [PMID: 25820723]
[99]
Betker, J.L.; Angle, B.M.; Graner, M.W.; Anchordoquy, T.J. The potential of exosomes from cow milk for oral delivery. J. Pharm. Sci., 2019, 108(4), 1496-1505.
[http://dx.doi.org/10.1016/j.xphs.2018.11.022 ] [PMID: 30468828]
[100]
Agrawal, A.K.; Aqil, F.; Jeyabalan, J.; Spencer, W.A.; Beck, J.; Gachuki, B.W.; Alhakeem, S.S.; Oben, K.; Munagala, R.; Bondada, S.; Gupta, R.C. Milk-derived exosomes for oral delivery of paclitaxel. Nanomedicine (Lond.), 2017, 13(5), 1627-1636.
[http://dx.doi.org/10.1016/j.nano.2017.03.001 ] [PMID: 28300659]
[101]
Aqil, F.; Munagala, R.; Jeyabalan, J.; Agrawal, A.K.; Kyakulaga, A-H.; Wilcher, S.A.; Gupta, R.C. Milk exosomes - Natural nanoparticles for siRNA delivery. Cancer Lett., 2019, 449, 186-195.
[http://dx.doi.org/10.1016/j.canlet.2019.02.011 ] [PMID: 30771430]
[102]
Mathivanan, S.; Lim, J.W.E.; Tauro, B.J.; Ji, H.; Moritz, R.L.; Simpson, R.J. Proteomics analysis of A33 immunoaffinity-purified exosomes released from the human colon tumor cell line LIM1215 reveals a tissue-specific protein signature. MCP, 2010, 9(2), 197-208.
[http://dx.doi.org/10.1074/mcp.M900152-MCP200]
[103]
Wubbolts, R.; Leckie, R.S.; Veenhuizen, P.T.; Schwarzmann, G.; Möbius, W.; Hoernschemeyer, J.; Slot, J.W.; Geuze, H.J.; Stoorvogel, W. Proteomic and biochemical analyses of human B cell-derived exosomes. Potential implications for their function and multivesicular body formation. J. Biol. Chem., 2003, 278(13), 10963-10972.
[http://dx.doi.org/10.1074/jbc.M207550200 ] [PMID: 12519789]
[104]
Dismuke, W.M.; Liu, Y. Current Methods to Purify and Characterize Exosomes.Mesenchymal Stem Cell Derived Exosomes;; Tang, Y.; Dawn, B., Eds.; Academic Press: Boston, 2015, pp. 63-92.
[http://dx.doi.org/10.1016/B978-0-12-800164-6.00004-6]
[105]
Witwer, K.W.; Buzás, E.I.; Bemis, L.T.; Bora, A.; Lässer, C.; Lötvall, J.; Nolte-’t Hoen, E.N.; Piper, M.G.; Sivaraman, S.; Skog, J.; Théry, C.; Wauben, M.H.; Hochberg, F. Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J. Extracell. Vesicles, 2013, 2, 20360.
[http://dx.doi.org/10.3402/jev.v2i0.20360 ] [PMID: 24009894]
[106]
Vaswani, K.; Koh, Y.Q.; Almughlliq, F.B.; Peiris, H.N.; Mitchell, M.D. A method for the isolation and enrichment of purified bovine milk exosomes. Reprod. Biol., 2017, 17(4), 341-348.
[http://dx.doi.org/10.1016/j.repbio.2017.09.007 ] [PMID: 29030127]
[107]
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.
[http://dx.doi.org/10.1038/mt.2010.105 ] [PMID: 20571541]
[108]
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.
[http://dx.doi.org/10.1007/s11095-014-1593-y ] [PMID: 25609010]
[109]
Kim, M.S.; Haney, M.J.; Zhao, Y.; Mahajan, V.; Deygen, I.; Klyachko, N.L.; Inskoe, E.; Piroyan, A.; Sokolsky, M.; Okolie, O.; Hingtgen, S.D.; Kabanov, A.V.; Batrakova, E.V. Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomedicine (Lond.), 2016, 12(3), 655-664.
[http://dx.doi.org/10.1016/j.nano.2015.10.012] [PMID: 26586551]
[110]
Bryniarski, K.; Ptak, W.; Jayakumar, A.; Püllmann, 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.
[http://dx.doi.org/10.1016/j.jaci.2013.04.048 ] [PMID: 23727037]
[111]
Fuhrmann, G.; Serio, A.; Mazo, M.; Nair, R.; Stevens, M.M. Active loading into extracellular vesicles significantly improves the cellular uptake and photodynamic effect of porphyrins. J. Control. Release, 2015, 205, 35-44.
[http://dx.doi.org/10.1016/j.jconrel.2014.11.029] [PMID: 25483424]
[112]
Gilligan, K.E.; Dwyer, R.M. Engineering exosomes for cancer therapy. Int. J. Mol. Sci., 2017, 18(6)E1122
[http://dx.doi.org/10.3390/ijms18061122] [PMID: 28538671]
[113]
Lu, M.; Xing, H.; Xun, Z.; Yang, T.; Ding, P.; Cai, C.; Wang, D.; Zhao, X. Exosome-based small RNA delivery: Progress and prospects. Asian J Pharm Sci, 2018, 13(1), 1-11.
[http://dx.doi.org/10.1016/j.ajps.2017.07.008] [PMID: 32104373]
[114]
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.
[http://dx.doi.org/10.1016/j.jconrel.2013.08.014] [PMID: 23994516]
[115]
Hood, J.L.; Scott, M.J.; Wickline, S.A. Maximizing exosome colloidal stability following electroporation. Anal. Biochem., 2014, 448, 41-49.
[http://dx.doi.org/10.1016/j.ab.2013.12.001] [PMID: 24333249]
[116]
Haney, M.J.; Klyachko, N.L.; Zhao, Y.; Gupta, R.; Plotnikova, E.G.; He, Z.; Patel, T.; Piroyan, A.; Sokolsky, M.; Kabanov, A.V.; Batrakova, E.V. Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J. Control. Release, 2015, 207, 18-30.
[http://dx.doi.org/10.1016/j.jconrel.2015.03.033] [PMID: 25836593]
[117]
Roberts, R.R.; Scott, R.D., II; Hota, B.; Kampe, L.M.; Abbasi, F.; Schabowski, S.; Ahmad, I.; Ciavarella, G.G.; Cordell, R.; Solomon, S.L.; Hagtvedt, R.; Weinstein, R.A. Costs attributable to healthcare-acquired infection in hospitalized adults and a comparison of economic methods. Med. Care, 2010, 48(11), 1026-1035.
[http://dx.doi.org/10.1097/MLR.0b013e3181ef60a2] [PMID: 20940650]
[118]
Izumi, H.; Kosaka, N.; Shimizu, T.; Sekine, K.; Ochiya, T.; Takase, M. Bovine milk contains microRNA and messenger RNA that are stable under degradative conditions. J. Dairy Sci., 2012, 95(9), 4831-4841.
[http://dx.doi.org/10.3168/jds.2012-5489] [PMID: 22916887]
[119]
Gu, Y.; Li, M.; Wang, T.; Liang, Y.; Zhong, Z.; Wang, X.; Zhou, Q.; Chen, L.; Lang, Q.; He, Z.; Chen, X.; Gong, J.; Gao, X.; Li, X.; Lv, X. Lactation-related microRNA expression profiles of porcine breast milk exosomes. PLoS One, 2012, 7(8)e43691
[http://dx.doi.org/10.1371/journal.pone.0043691] [PMID: 22937080]
[120]
Benmoussa, A.; Lee, C.H.; Laffont, B.; Savard, P.; Laugier, J.; Boilard, E.; Gilbert, C.; Fliss, I.; Provost, P. Commercial dairy cow milk microRNAs resist digestion under simulated gastrointestinal tract conditions. J. Nutr., 2016, 146(11), 2206-2215.
[http://dx.doi.org/10.3945/jn.116.237651] [PMID: 27708120]
[121]
Vashisht, M.; Rani, P.; Onteru, S.K.; Singh, D. Curcumin encapsulated in milk exosomes resists human digestion and possesses enhanced intestinal permeability in vitro. Appl. Biochem. Biotechnol., 2017, 183(3), 993-1007.
[http://dx.doi.org/10.1007/s12010-017-2478-4] [PMID: 28466459]
[122]
Wolf, T.; Baier, S.R.; Zempleni, J. The intestinal transport of bovine milk exosomes is mediated by endocytosis in human colon carcinoma caco-2 cells and rat small intestinal IEC-6 cells. J. Nutr., 2015, 145(10), 2201-2206.
[http://dx.doi.org/10.3945/jn.115.218586] [PMID: 26269243]
[123]
Kusuma, R.J.; Manca, S.; Friemel, T.; Sukreet, S.; Nguyen, C.; Zempleni, J. Human vascular endothelial cells transport foreign exosomes from cow’s milk by endocytosis. Am. J. Physiol. Cell Physiol., 2016, 310(10), C800-C807.
[http://dx.doi.org/10.1152/ajpcell.00169.2015] [PMID: 26984735]
[124]
Kandela, I.; Chou, J.; Chow, K. Reproducibility Project: Cancer Biology. Registered report: Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs. eLife, 2015, 4e06959
[http://dx.doi.org/10.7554/eLife.06959] [PMID: 27879198]
[125]
Sugahara, K.N.; Teesalu, T.; Karmali, P.P.; Kotamraju, V.R.; Agemy, L.; Girard, O.M.; Hanahan, D.; Mattrey, R.F.; Ruoslahti, E. Tissue-penetrating delivery of compounds and nanoparticles into tumors. Cancer Cell, 2009, 16(6), 510-520.
[http://dx.doi.org/10.1016/j.ccr.2009.10.013] [PMID: 19962669]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy