Targeted therapeutic delivery using engineered exosomes and its applications in cardiovascular diseases

Gene

Volumn 575, Issue 2, 2016, Pages 377-384

  Xitong, Dang ^a   Xiaorong, Zeng ^a  

^a BEIJING UNIVERSITY OF POSTS AND TELECOMMUNICATIONS   (China)

Author keywords

Cardiovascular disease; Exosome; Genetic engineering; MiRNA; Phage display; Targeted gene therapy

Indexed keywords

MICRORNA; PEPTIDE;

CARDIOVASCULAR DISEASE; CELL COMMUNICATION; CELL ENGINEERING; CELL FUNCTION; CELL ISOLATION; CELL MIGRATION; EXOSOME; GENE DELIVERY SYSTEM; HUMAN; NONHUMAN; ORGANELLE BIOGENESIS; PRIORITY JOURNAL; PROTEIN TARGETING; PURIFICATION; REVIEW; ANTIBODY SPECIFICITY; CARDIOVASCULAR DISEASES; DRUG DELIVERY SYSTEM; PHYSIOLOGY; SECRETION (PROCESS);

CARDIOVASCULAR DISEASES; CELL COMMUNICATION; DRUG DELIVERY SYSTEMS; EXOSOMES; HUMANS; MICRORNAS; ORGAN SPECIFICITY; PEPTIDES;

EID: 84940847279     PISSN: 03781119     EISSN: 18790038     Source Type: Journal    
DOI: 10.1016/j.gene.2015.08.067     Document Type: Review

References (99)

1. Adlakha Y.K., Saini N. Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128. Mol. Cancer 2014, 13:33. 10.1186/1476-4598-13-33.
2. Alvarez-Erviti L., Seow Y., Yin H., Betts C., Lakhal S., Wood M.J. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat. Biotechnol. 2011, 29:341-345. 10.1038/nbt.1807.
3. Andre F., Chaput N., Schartz N.E., Flament C., Aubert N., Bernard J., Lemonnier F., Raposo G., Escudier B., Hsu D.H., Tursz T., Amigorena S., Angevin E., Zitvogel L. Exosomes as potent cell-free peptide-based vaccine. I. Dendritic cell-derived exosomes transfer functional MHC class I/peptide complexes to dendritic cells. J. Immunol. 2004, 172:2126-2136.
4. Andreou I., Sun X., Stone P.H., Edelman E.R., Feinberg M.W. miRNAs in atherosclerotic plaque initiation, progression, and rupture. Trends Mol. Med. 2015, 21:307-318. 10.1016/j.molmed.2015.02.003.
5. Arnesen T. Towards a functional understanding of protein N-terminal acetylation. PLoS Biol. 2011, 9:e1001074. 10.1371/journal.pbio.1001074.
6. Balaj L., Atai N.A., Chen W., Mu D., Tannous B.A., Breakefield X.O., Skog J., Maguire C.A. Heparin affinity purification of extracellular vesicles. Sci. Rep. 2015, 5:10266. 10.1038/srep10266.
7. Bang C., Batkai S., Dangwal S., Gupta S.K., Foinquinos A., Holzmann A., Just A., Remke J., Zimmer K., Zeug A., Ponimaskin E., Schmiedl A., Yin X., Mayr M., Halder R., Fischer A., Engelhardt S., Wei Y., Schober A., Fiedler J., Thum T. Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy. J. Clin. Invest. 2014, 124:2136-2146. 10.1172/JCI70577.
8. Boukouris S., Mathivanan S. Exosomes in bodily fluids are a highly stable resource of disease biomarkers. Proteomics Clin. Appl. 2015, 9:358-367. 10.1002/prca.201400114.
9. Cakmak H.A., Coskunpinar E., Ikitimur B., Barman H.A., Karadag B., Tiryakioglu N.O., Kahraman K., Vural V.A. The prognostic value of circulating microRNAs in heart failure: preliminary results from a genome-wide expression study. J. Cardiovasc. Med. (Hagerstown) 2015, 16:431-437. 10.2459/JCM.0000000000000233.
10. Cervio E., Barile L., Moccetti T., Vassalli G. Exosomes for intramyocardial intercellular communication. Stem Cells Int. 2015, 2015:482171. 10.1155/2015/482171.
11. Chen L., Wang Y., Pan Y., Zhang L., Shen C., Qin G., Ashraf M., Weintraub N., Ma G., Tang Y. Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury. Biochem. Biophys. Res. Commun. 2013, 431:566-571. 10.1016/j.bbrc.2013.01.015.
12. Cheng L., Sharples R.A., Scicluna B.J., Hill A.F. Exosomes provide a protective and enriched source of miRNA for biomarker profiling compared to intracellular and cell-free blood. J. Extracell Vesicles 2014, 3. 10.3402/jev.v3.23743.
13. Choi D.S. Urinary extracellular vesicles for biomarker source to monitor polycystic kidney disease. Proteomics Clin. Appl 2015, 10.1002/prca.201500053.
14. Chugh P.E., Sin S.H., Ozgur S., Henry D.H., Menezes P., Griffith J., Eron J.J., Damania B., Dittmer D.P. Systemically circulating viral and tumor-derived microRNAs in KSHV-associated malignancies. PLoS Pathog. 2013, 9:e1003484. 10.1371/journal.ppat.1003484.
15. Cooper J.M., Wiklander P.B., Nordin J.Z., Al-Shawi R., Wood M.J., Vithlani M., Schapira A.H., Simons J.P., El-Andaloussi S., Alvarez-Erviti L. Systemic exosomal siRNA delivery reduced alpha-synuclein aggregates in brains of transgenic mice. Mov. Disord. 2014, 29:1476-1485. 10.1002/mds.25978.
16. Costantini T.W., Putnam J.G., Sawada R., Baird A., Loomis W.H., Eliceiri B.P., Bansal V., Coimbra R. Targeting the gut barrier: identification of a homing peptide sequence for delivery into the injured intestinal epithelial cell. Surgery 2009, 146:206-212. 10.1016/j.surg.2009.05.007.
17. Costantini T.W., Eliceiri B.P., Putnam J.G., Bansal V., Baird A., Coimbra R. Intravenous phage display identifies peptide sequences that target the burn-injured intestine. Peptides 2012, 38:94-99. 10.1016/j.peptides.2012.08.015.
18. Das S., Halushka M.K. Extracellular vesicle microRNA transfer in cardiovascular disease. Cardiovasc. Pathol. 2015, 10.1016/j.carpath.2015.04.007.
19. de Menezes-Neto A., Saez M.J., Lozano-Ramos I., Segui-Barber J., Martin-Jaular L., Ullate J.M., Fernandez-Becerra C., Borras F.E., Del Portillo H.A. Size-exclusion chromatography as a stand-alone methodology identifies novel markers in mass spectrometry analyses of plasma-derived vesicles from healthy individuals. J. Extracell Vesicles 2015, 4:27378. 10.3402/jev.v4.27378.
20. Delcayre A., Estelles A., Sperinde J., Roulon T., Paz P., Aguilar B., Villanueva J., Khine S., Le Pecq J.B. Exosome display technology: applications to the development of new diagnostics and therapeutics. Blood Cells Mol. Dis. 2005, 35:158-168. 10.1016/j.bcmd.2005.07.003.
21. 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.
22. D'Onofrio N., Caraglia M., Grimaldi A., Marfella R., Servillo L., Paolisso G., Balestrieri M.L. Vascular-homing peptides for targeted drug delivery and molecular imaging: meeting the clinical challenges. Biochim. Biophys. Acta 2014, 1846:1-12. 10.1016/j.bbcan.2014.03.004.
23. El-Andaloussi S., Lee Y., Lakhal-Littleton S., Li J., Seow Y., Gardiner C., Alvarez-Erviti L., Sargent I.L., Wood M.J. Exosome-mediated delivery of siRNA in vitro and in vivo. Nat. Protoc. 2012, 7:2112-2126. 10.1038/nprot.2012.131.
24. Emanueli C., Shearn A.I., Angelini G.D., Sahoo S. Exosomes and exosomal miRNAs in cardiovascular protection and repair. Vasc. Pharmacol. 2015, 10.1016/j.vph.2015.02.008.
25. Estelles A., Sperinde J., Roulon T., Aguilar B., Bonner C., LePecq J.B., Delcayre A. Exosome nanovesicles displaying G protein-coupled receptors for drug discovery. Int. J. Nanomedicine 2007, 2:751-760.
26. Fais S., Logozzi M., Lugini L., Federici C., Azzarito T., Zarovni N., Chiesi A. Exosomes: the ideal nanovectors for biodelivery. Biol. Chem. 2013, 394:1-15. 10.1515/hsz-2012-0236.
27. Fan G.C. Hypoxic exosomes promote angiogenesis. Blood 2014, 124:3669-3670. 10.1182/blood-2014-10-607846.
28. Ferreira L.R., Frade A.F., Santos R.H., Teixeira P.C., Baron M.A., Navarro I.C., Benvenuti L.A., Fiorelli A.I., Bocchi E.A., Stolf N.A., Chevillard C., Kalil J., Cunha-Neto E. MicroRNAs miR-1, miR-133a, miR-133b, miR-208a and miR-208b are dysregulated in Chronic Chagas disease Cardiomyopathy. Int. J. Cardiol. 2014, 175:409-417. 10.1016/j.ijcard.2014.05.019.
29. Foglio E., Puddighinu G., Fasanaro P., D'Arcangelo D., Perrone G.A., Mocini D., Campanella C., Coppola L., Logozzi M., Azzarito T., Marzoli F., Fais S., Pieroni L., Marzano V., Germani A., Capogrossi M.C., Russo M.A., Limana F. Exosomal clusterin, identified in the pericardial fluid, improves myocardial performance following MI through epicardial activation, enhanced arteriogenesis and reduced apoptosis. Int. J. Cardiol. 2015, 197:333-347. 10.1016/j.ijcard.2015.06.008.
30. Ghosh A., Davey M., Chute I.C., Griffiths S.G., Lewis S., Chacko S., Barnett D., Crapoulet N., Fournier S., Joy A., Caissie M.C., Ferguson A.D., Daigle M., Meli M.V., Lewis S.M., Ouellette R.J. Rapid isolation of extracellular vesicles from cell culture and biological fluids using a synthetic peptide with specific affinity for heat shock proteins. PLoS One 2014, 9:e110443. 10.1371/journal.pone.0110443.
31. Gough N.R., Zweifel M.E., Martinez-Augustin O., Aguilar R.C., Bonifacino J.S., Fambrough D.M. Utilization of the indirect lysosome targeting pathway by lysosome-associated membrane proteins (LAMPs) is influenced largely by the C-terminal residue of their GYXXphi targeting signals. J. Cell Sci. 1999, 112(Pt 23):4257-4269.
32. Gould D.J., Favorov P. Vectors for the treatment of autoimmune disease. Gene Ther. 2003, 10:912-927. 10.1038/sj.gt.3302018.
33. Greenberg B. Gene therapy for heart failure. J. Cardiol. 2015, 10.1016/j.jjcc.2015.02.006.
34. Hall J.L. Exosomes decrease infarct size. J. Am. Coll. Cardiol. 2015, 65:1537-1538. 10.1016/j.jacc.2015.02.028.
35. Hammoudi N., Ishikawa K., Hajjar R.J. Adeno-associated virus-mediated gene therapy in cardiovascular disease. Curr. Opin. Cardiol. 2015, 30:228-234. 10.1097/HCO.0000000000000159.
36. 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. 10.1016/j.jconrel.2015.03.033.
37. Hartman Z.C., Wei J., Glass O.K., Guo H., Lei G., Yang X.Y., Osada T., Hobeika A., Delcayre A., Le Pecq J.B., Morse M.A., Clay T.M., Lyerly H.K. Increasing vaccine potency through exosome antigen targeting. Vaccine 2011, 29:9361-9367. 10.1016/j.vaccine.2011.09.133.
38. Hessels D., Schalken J.A. Urinary biomarkers for prostate cancer: a review. Asian J. Androl. 2013, 15:333-339. 10.1038/aja.2013.6.
39. Hong H.Y., Lee H.Y., Kwak W., Yoo J., Na M.H., So I.S., Kwon T.H., Park H.S., Huh S., Oh G.T., Kwon I.C., Kim I.S., Lee B.H. Phage display selection of peptides that home to atherosclerotic plaques: IL-4 receptor as a candidate target in atherosclerosis. J. Cell. Mol. Med. 2008, 12:2003-2014. 10.1111/j.1582-4934.2008.00189.x.
40. Hung M.E., Leonard J.N. Stabilization of exosome-targeting peptides via engineered glycosylation. J. Biol. Chem. 2015, 290:8166-8172. 10.1074/jbc.M114.621383.
41. Kanki S., Jaalouk D.E., Lee S., Yu A.Y., Gannon J., Lee R.T. Identification of targeting peptides for ischemic myocardium by in vivo phage display. J. Mol. Cell. Cardiol. 2011, 50:841-848. 10.1016/j.yjmcc.2011.02.003.
42. Keerthikumar S., Gangoda L., Liem M., Fonseka P., Atukorala I., Ozcitti C., Mechler A., Adda C.G., Ang C.S., Mathivanan S. Proteogenomic analysis reveals exosomes are more oncogenic than ectosomes. Oncotarget 2015.
43. Keller S., Sanderson M.P., Stoeck A., Altevogt P. Exosomes: from biogenesis and secretion to biological function. Immunol. Lett. 2006, 107:102-108. 10.1016/j.imlet.2006.09.005.
44. Khan M., Nickoloff E., Abramova T., Johnson J., Verma S.K., Krishnamurthy P., Mackie A.R., Vaughan E., Garikipati V.N., Benedict C.L., Ramirez V., Lambers E., Ito A., Gao E., Misener S., Qin G., Luongo T.S., Elrod J.W., Houser S.R., Koch W.J., Kishore R. Embryonic stem cell-derived exosomes promote endogenous repair mechanisms and enhance cardiac function following myocardial infarction. Circ. Res. 2015, 10.1161/CIRCRESAHA.117.305990.
45. Klein-Scory S., Tehrani M.M., Eilert-Micus C., Adamczyk K.A., Wojtalewicz N., Schnolzer M., Hahn S.A., Schmiegel W., Schwarte-Waldhoff I. New insights in the composition of extracellular vesicles from pancreatic cancer cells: implications for biomarkers and functions. Proteome Sci. 2014, 12:50. 10.1186/s12953-014-0050-5.
46. 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. 10.2147/IJN.S29661.
47. Lakhal S., Wood M.J. Exosome nanotechnology: an emerging paradigm shift in drug delivery: exploitation of exosome nanovesicles for systemic in vivo delivery of RNAi heralds new horizons for drug delivery across biological barriers. BioEssays 2011, 33:737-741. 10.1002/bies.201100076.
48. Lee G.Y., Kim J.H., Oh G.T., Lee B.H., Kwon I.C., Kim I.S. Molecular targeting of atherosclerotic plaques by a stabilin-2-specific peptide ligand. J. Control. Release 2011, 155:211-217. 10.1016/j.jconrel.2011.07.010.
49. Lee K.J., Lee J.H., Chung H.K., Choi J., Park J., Park S.S., Ju E.J., Shin S.H., Park H.J., Ko E.J., Suh N., Kim I., Hwang J.J., Song S.Y., Jeong S.Y., Choi E.K. Novel peptides functionally targeting in vivo human lung cancer discovered by in vivo peptide displayed phage screening. Amino Acids 2015, 47:281-289. 10.1007/s00726-014-1852-6.
50. Lee K., Yu P., Lingampalli N., Kim H.J., Tang R., Murthy N. Peptide-enhanced mRNA transfection in cultured mouse cardiac fibroblasts and direct reprogramming towards cardiomyocyte-like cells. Int. J. Nanomedicine 2015, 10:1841-1854. 10.2147/IJN.S75124.
51. Li Z., Zhao R., Wu X., Sun Y., Yao M., Li J., Xu Y., Gu J. Identification and characterization of a novel peptide ligand of epidermal growth factor receptor for targeted delivery of therapeutics. FASEB J. 2005, 19:1978-1985. 10.1096/fj.05-4058com.
52. Lorenzen J.M., Batkai S., Thum T. Regulation of cardiac and renal ischemia-reperfusion injury by microRNAs. Free Radic. Biol. Med. 2013, 64:78-84. 10.1016/j.freeradbiomed.2013.06.044.
53. Lozano-Ramos I., Bancu I., Oliveira-Tercero A., Armengol M.P., Menezes-Neto A., Del Portillo H.A., Lauzurica-Valdemoros R., Borras F.E. Size-exclusion chromatography-based enrichment of extracellular vesicles from urine samples. J. Extracell Vesicles 2015, 4:27369. 10.3402/jev.v4.27369.
54. Madison M.N., Roller R.J., Okeoma C.M. Human semen contains exosomes with potent anti-HIV-1 activity. Retrovirology 2014, 11:102. 10.1186/s12977-014-0102-z.
55. Marcus M.E., Leonard J.N. FedExosomes: engineering therapeutic biological nanoparticles that truly deliver. Pharmaceuticals (Basel) 2013, 6:659-680. 10.3390/ph6050659.
56. Mathivanan S., Ji H., Simpson R.J. Exosomes: extracellular organelles important in intercellular communication. J. Proteome 2010, 73:1907-1920. 10.1016/j.jprot.2010.06.006.
57. Matkovich S.J., Dorn G.W. Deep sequencing of cardiac microRNA-mRNA interactomes in clinical and experimental cardiomyopathy. Methods Mol. Biol. 2015, 1299:27-49. 10.1007/978-1-4939-2572-8_3.
58. Moreno-Gonzalo O., Villarroya-Beltri C., Sanchez-Madrid F. Post-translational modifications of exosomal proteins. Front. Immunol. 2014, 5:383. 10.3389/fimmu.2014.00383.
59. Mulcahy L.A., Pink R.C., Carter D.R. Routes and mechanisms of extracellular vesicle uptake. J. Extracell Vesicles 2014, 3. 10.3402/jev.v3.24641.
60. Munich S., Sobo-Vujanovic A., Buchser W.J., Beer-Stolz D., Vujanovic N.L. Dendritic cell exosomes directly kill tumor cells and activate natural killer cells via TNF superfamily ligands. Oncoimmunology 2012, 1:1074-1083. 10.4161/onci.20897.
61. Ogawa Y., Miura Y., Harazono A., Kanai-Azuma M., Akimoto Y., Kawakami H., Yamaguchi T., Toda T., Endo T., Tsubuki M., Yanoshita R. Proteomic analysis of two types of exosomes in human whole saliva. Biol. Pharm. Bull. 2011, 34:13-23.
62. Ogorevc E., Kralj-Iglic V., Veranic P. The role of extracellular vesicles in phenotypic cancer transformation. Radiol. Oncol. 2013, 47:197-205. 10.2478/raon-2013-0037.
63. 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, 21:185-191. 10.1038/mt.2012.180.
64. O'Loughlin A.J., Woffindale C.A., Wood M.J. Exosomes and the emerging field of exosome-based gene therapy. Curr. Gene Ther. 2012, 12:262-274.
65. 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, 33:967-978.
66. Pang H.B., Braun G.B., She Z.G., Kotamraju V.R., Sugahara K.N., Teesalu T., Ruoslahti E. A free cysteine prolongs the half-life of a homing peptide and improves its tumor-penetrating activity. J. Control. Release 2014, 175:48-53. 10.1016/j.jconrel.2013.12.006.
67. Raimondo S., Saieva L., Corrado C., Fontana S., Flugy A., Rizzo A., De Leo G., Alessandro R. Chronic myeloid leukemia-derived exosomes promote tumor growth through an autocrine mechanism. Cell Commun. Signal. 2015, 13:8. 10.1186/s12964-015-0086-x.
68. Raposo G., Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J. Cell Biol. 2013, 200:373-383. 10.1083/jcb.201211138.
69. 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, 183:1161-1172.
70. Rountree R.B., Mandl S.J., Nachtwey J.M., Dalpozzo K., Do L., Lombardo J.R., Schoonmaker P.L., Brinkmann K., Dirmeier U., Laus R., Delcayre A. Exosome targeting of tumor antigens expressed by cancer vaccines can improve antigen immunogenicity and therapeutic efficacy. Cancer Res. 2011, 71:5235-5244. 10.1158/0008-5472.CAN-10-4076.
71. Ruvkun G. Molecular biology. glimpses of a tiny RNA world. Science 2001, 294:797-799. 10.1126/science.1066315.
72. Sahoo S., Losordo D.W. Exosomes and cardiac repair after myocardial infarction. Circ. Res. 2014, 114:333-344. 10.1161/CIRCRESAHA.114.300639.
73. Schorey J.S., Bhatnagar S. Exosome function: from tumor immunology to pathogen biology. Traffic 2008, 9:871-881. 10.1111/j.1600-0854.2008.00734.x.
74. Sedlik C., Vigneron J., Torrieri-Dramard L., Pitoiset F., Denizeau J., Chesneau C., de la Rochere P., Lantz O., Thery C., Bellier B. Different immunogenicity but similar antitumor efficacy of two DNA vaccines coding for an antigen secreted in different membrane vesicle-associated forms. J. Extracell Vesicles 2014, 3. 10.3402/jev.v3.24646.
75. Sekar T.V., Mohanram R.K., Foygel K., Paulmurugan R. Therapeutic evaluation of microRNAs by molecular imaging. Theranostics 2013, 3:964-985. 10.7150/thno.4928.
76. 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. 10.1186/1478-811X-11-88.
77. Smith G.P. Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science 1985, 228:1315-1317.
78. Smyth T., Kullberg M., Malik N., Smith-Jones P., Graner M.W., Anchordoquy T.J. Biodistribution and delivery efficiency of unmodified tumor-derived exosomes. J. Control. Release 2015, 199:145-155. 10.1016/j.jconrel.2014.12.013.
79. Srinivasan S., Selvan S.T., Archunan G., Gulyas B., Padmanabhan P. MicroRNAs - the next generation therapeutic targets in human diseases. Theranostics 2013, 3:930-942. 10.7150/thno.7026.
80. Stahl P.D., Barbieri M.A. Multivesicular bodies and multivesicular endosomes: the "ins and outs" of endosomal traffic. Sci. STKE 2002, 2002:pe32.doi: 10.1126/stke.2002.141.pe32.
81. Stather P.W., Sylvius N., Sidloff D.A., Dattani N., Verissimo A., Wild J.B., Butt H.Z., Choke E., Sayers R.D., Bown M.J. Identification of microRNAs associated with abdominal aortic aneurysms and peripheral arterial disease. Br. J. Surg. 2015, 102:755-766. 10.1002/bjs.9802.
82. Stoorvogel W. Resolving sorting mechanisms into exosomes. Cell Res. 2015, 25:531-532. 10.1038/cr.2015.39.
83. Taraboletti G., D'Ascenzo S., Giusti I., Marchetti D., Borsotti P., Millimaggi D., Giavazzi R., Pavan A., Dolo V. Bioavailability of VEGF in tumor-shed vesicles depends on vesicle burst induced by acidic pH. Neoplasia 2006, 8:96-103. 10.1593/neo.05583.
84. Thapa N., Hong H.Y., Sangeetha P., Kim I.S., Yoo J., Rhee K., Oh G.T., Kwon I.C., Lee B.H. Identification of a peptide ligand recognizing dysfunctional endothelial cells for targeting atherosclerosis. J. Control. Release 2008, 131:27-33. 10.1016/j.jconrel.2008.07.013.
85. 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, Chapter 3:Unit 3 22. doi: 10.1002/0471143030.cb0322s30.
86. 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, 35:2383-2390. 10.1016/j.biomaterials.2013.11.083.
87. Toba M., Alzoubi A., O'Neill K., Abe K., Urakami T., Komatsu M., Alvarez D., Jarvinen T.A., Mann D., Ruoslahti E., McMurtry I.F., Oka M. A novel vascular homing peptide strategy to selectively enhance pulmonary drug efficacy in pulmonary arterial hypertension. Am. J. Pathol. 2014, 184:369-375. 10.1016/j.ajpath.2013.10.008.
88. Van Niel G., Mallegol J., Bevilacqua C., Candalh C., Brugiere S., Tomaskovic-Crook E., Heath J.K., Cerf-Bensussan N., Heyman M. Intestinal epithelial exosomes carry MHC class II/peptides able to inform the immune system in mice. Gut 2003, 52:1690-1697.
89. Vella L.J., Greenwood D.L., Cappai R., Scheerlinck J.P., Hill A.F. Enrichment of prion protein in exosomes derived from ovine cerebral spinal fluid. Vet. Immunol. Immunopathol. 2008, 124:385-393. 10.1016/j.vetimm.2008.04.002.
90. Vicencio J.M., Yellon D.M., Sivaraman V., Das D., Boi-Doku C., Arjun S., Zheng Y., Riquelme J.A., Kearney J., Sharma V., Multhoff G., Hall A.R., Davidson S.M. Plasma exosomes protect the myocardium from ischemia-reperfusion injury. J. Am. Coll. Cardiol. 2015, 65:1525-1536. 10.1016/j.jacc.2015.02.026.
91. Villarroya-Beltri C., Baixauli F., Gutierrez-Vazquez C., Sanchez-Madrid F., Mittelbrunn M. Sorting it out: regulation of exosome loading. Semin. Cancer Biol. 2014, 28:3-13. 10.1016/j.semcancer.2014.04.009.
92. 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, 1820:940-948. 10.1016/j.bbagen.2012.03.017.
93. Wallace R.J. Acetylation of peptides inhibits their degradation by rumen micro-organisms. Br. J. Nutr. 1992, 68:365-372.
94. Wang H., Jiang Y., Peng H., Chen Y., Zhu P., Huang Y. Recent progress in microRNA delivery for cancer therapy by non-viral synthetic vectors. Adv. Drug Deliv. Rev. 2015, 81:142-160. 10.1016/j.addr.2014.10.031.
95. Wang Y., Zhang L., Li Y., Chen L., Wang X., Guo W., Zhang X., Qin G., He S.H., Zimmerman A., Liu Y., Kim I.M., Weintraub N.L., Tang Y. Exosomes/microvesicles from induced pluripotent stem cells deliver cardioprotective miRNAs and prevent cardiomyocyte apoptosis in the ischemic myocardium. Int. J. Cardiol. 2015, 192:61-69. 10.1016/j.ijcard.2015.05.020.
96. Won Y.W., McGinn A.N., Lee M., Bull D.A., Kim S.W. Targeted gene delivery to ischemic myocardium by homing peptide-guided polymeric carrier. Mol. Pharm. 2013, 10:378-385. 10.1021/mp300500y.
97. Yu K.F., Zhang W.Q., Luo L.M., Song P., Li D., Du R., Ren W., Huang D., Lu W.L., Zhang X., Zhang Q. The antitumor activity of a doxorubicin loaded, iRGD-modified sterically-stabilized liposome on B16-F10 melanoma cells: in vitro and in vivo evaluation. Int. J. Nanomedicine 2013, 8:2473-2485. 10.2147/IJN.S46962.
98. Zhang Y., Wang Z., Gemeinhart R.A. Progress in microRNA delivery. J. Control. Release 2013, 172:962-974. 10.1016/j.jconrel.2013.09.015.
99. Zhang J., Li S., Li L., Li M., Guo C., Yao J., Mi S. Exosome and exosomal microRNA: trafficking, sorting, and function. Genomics Proteomics Bioinformatics 2015, 13:17-24. 10.1016/j.gpb.2015.02.001.