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A pharmaceutical investigation into exosomes

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Abstract

During the last 5 years, there has been a marked rise in publications regarding exosomes. Exosomes find potential applications as diagnostic biomarkers, therapeutics, drug delivery vehicles, and functional cosmetics and several exosome-based therapies are under clinical trials. Exosomes are nanosized vesicles that contain cell-derived lipid membranes, nucleic acids, and proteins, and are released from the cells of origin, circulate in eukaryotic fluids, and are taken up by recipient cells. The originating cell can be engineered to express specific genes, which enhance immunity, cross-presentation of antigens, or cell targeting by exosomes. Various methods using centrifugation, size-exclusion chromatography, filtration, precipitation, affinity, and microfluidics have been assessed for the isolation and purification of exosomes from biological samples. In addition, exosomes have advantages as drug delivery systems, with biocompatibility, preservation of cargo drugs during circulation in physiological fluids, uptake into the target cells, and drug release after endosomal escape. In this review, we discuss the various aspects of pharmaceutical investigation into exosomes with special focus on engineering, production, characterization, biological activities, applications of exosomes as drug delivery systems, and regulations for evaluation of exosome products.

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References

  • Alvarez ML, Khosroheidari M, Ravi RK, DiStefano JK (2012) Comparison of protein, microRNA, and mRNA yields using different methods of urinary exosome isolation for the discovery of kidney disease biomarkers. Kidney Int 82:1024–1032

    Article  CAS  PubMed  Google Scholar 

  • Baranyai T, Herczeg K, Onodi Z, Voszka I, Modos K, Marton N, Nagy G, Mager I, Wood MJ, El Andaloussi S, Palinkas Z, Kumar V, Nagy P, Kittel A, Buzas EI, Ferdinandy P, Giricz Z (2015) Isolation of exosomes from blood plasma: qualitative and quantitative comparison of ultracentrifugation and size exclusion chromatography methods. PLoS One 10:e0145686

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boing AN, van der Pol E, Grootemaat AE, Coumans FA, Sturk A, Nieuwland R (2014) Single-step isolation of extracellular vesicles by size-exclusion chromatography. J Extracell Vesicles 3

  • Booth AM, Fang Y, Fallon JK, Yang JM, Hildreth JE, Gould SJ (2006) Exosomes and HIV Gag bud from endosome-like domains of the T cell plasma membrane. J Cell Biol 172:923–935

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bosch S, De Beaurepaire L, Allard M, Mosser M, Heichette C, Chrétien D, Jegou D, Bach J-M (2016) Trehalose prevents aggregation of exosomes and cryodamage. Sci Rep Uk 6:36162

    Article  CAS  Google Scholar 

  • Chavez-Munoz C, Morse J, Kilani R, Ghahary A (2008) Primary human keratinocytes externalize stratifin protein via exosomes. J Cell Biochem 104:2165–2173

    Article  CAS  PubMed  Google Scholar 

  • Cheruvanky A, Zhou H, Pisitkun T, Kopp JB, Knepper MA, Yuen PS, Star RA (2007) Rapid isolation of urinary exosomal biomarkers using a nanomembrane ultrafiltration concentrator. Am J Physiol Renal Physiol 292:F1657-F1661

    Article  CAS  PubMed Central  Google Scholar 

  • Choi JS, Yoon HI, Lee KS, Choi YC, Yang SH, Kim IS, Cho YW (2016) Exosomes from differentiating human skeletal muscle cells trigger myogenesis of stem cells and provide biochemical cues for skeletal muscle regeneration. J Control Releas 222:107–115

    Article  CAS  Google Scholar 

  • Clark NA, Lunacek JH, Benedek GB (1970) A study of Brownian motion using light scattering. Am J Phys 38:575–585

    Article  Google Scholar 

  • Cui Y, Luan J, Li H, Zhou X, Han J (2016) Exosomes derived from mineralizing osteoblasts promote ST2 cell osteogenic differentiation by alteration of microRNA expression. FEBS Lett 590:185–192

    Article  CAS  PubMed  Google Scholar 

  • de Vrij J, Maas SL, van Nispen M, Sena-Esteves M, Limpens RW, Koster AJ, Leenstra S, Lamfers ML, Broekman ML (2013) Quantification of nanosized extracellular membrane vesicles with scanning ion occlusion sensing. Nanomedicine (Lond) 8:1443–1458

    Article  CAS  Google Scholar 

  • Di Bonito P, Ridolfi B, Columba-Cabezas S, Giovannelli A, Chiozzini C, Manfredi F, Anticoli S, Arenaccio C, Federico M (2015) HPV-E7 delivered by engineered exosomes elicits a protective CD8(+) T cell-mediated immune response. Viruses 7:1079–1099

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Di Bonito P, Chiozzini C, Arenaccio C, Anticoli S, Manfredi F, Olivetta E, Ferrantelli F, Falcone E, Ruggieri A, Federico M (2017) Antitumor HPV E7-specific CTL activity elicited by in vivo engineered exosomes produced through DNA inoculation. Int J Nanomed 12:4579–4591

    Article  Google Scholar 

  • Dukers DF, Meij P, Vervoort MB, Vos W, Scheper RJ, Meijer CJ, Bloemena E, Middeldorp JM (2000) Direct immunosuppressive effects of EBV-encoded latent membrane protein 1. J Immunol 165:663–670

    Article  CAS  PubMed  Google Scholar 

  • Escola JM, Kleijmeer MJ, Stoorvogel W, Griffith JM, Yoshie O, Geuze HJ (1998) Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes. J Biol Chem 273:20121–20127

    Article  CAS  PubMed  Google Scholar 

  • Filipe V, Hawe A, Jiskoot W (2010) Critical evaluation of nanoparticle tracking analysis (NTA) by NanoSight for the measurement of nanoparticles and protein aggregates. Pharm Res 27:796–810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Geminard C, De Gassart A, Blanc L, Vidal M (2004) Degradation of AP2 during reticulocyte maturation enhances binding of hsc70 and Alix to a common site on TFR for sorting into exosomes. Traffic 5:181–193

    Article  CAS  PubMed  Google Scholar 

  • Gimona M, Pachler K, Laner-Plamberger S, Schallmoser K, Rohde E (2017) Manufacturing of human extracellular vesicle-based therapeutics for clinical use. Int J Mol Sci 18

  • Gruenberg J, Van der Goot FG (2006) Mechanisms of pathogen entry through the endosomal compartments. Nat Rev Mol Cell Biol 7:495

    Article  CAS  PubMed  Google Scholar 

  • Haney MJ, Klyachko NL, Zhao Y, Gupta R, Plotnikova EG, He Z, Patel T, Piroyan A, Sokolsky M, Kabanov AV, Batrakova EV (2015) Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J Control Release 207:18–30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heijnen HF, Schiel AE, Fijnheer R, Geuze HJ, Sixma JJ (1999) Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules. Blood 94:3791–3799

    CAS  PubMed  Google Scholar 

  • Heinemann ML, Ilmer M, Silva LP, Hawke DH, Recio A, Vorontsova MA, Alt E, Vykoukal J (2014) Benchtop isolation and characterization of functional exosomes by sequential filtration. J Chromatogr A 1371:125–135

    Article  CAS  PubMed  Google Scholar 

  • Illes B, Hirschle P, Barnert S, Cauda V, Wuttke S, Engelke H (2017) Exosome-coated metal-organic framework nanoparticles: an efficient drug delivery platform. Chem Mater 29:8042–8046

    Article  CAS  Google Scholar 

  • Im H, Shao H, Park YI, Peterson VM, Castro CM, Weissleder R, Lee H (2014) Label-free detection and molecular profiling of exosomes with a nano-plasmonic sensor. Nat Biotechnol 32:490–495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jarad M, Kuczynski E, Morrison J, Viloria-Petit A, Coomber B (2017) Release of endothelial cell associated VEGFR2 during TGF-β modulated angiogenesis in vitro. BMC Cell Biol 18:10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jeong S, Park J, Pathania D, Castro CM, Weissleder R, Lee H (2016) Integrated magneto-electrochemical sensor for exosome analysis. ACS Nano 10:1802–1809

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jia S, Zocco D, Samuels ML, Chou MF, Chammas R, Skog J, Zarovni N, Momen-Heravi F, Kuo WP (2014) Emerging technologies in extracellular vesicle-based molecular diagnostics. Expert Rev Mol Diagn 14:307–321

    Article  CAS  PubMed  Google Scholar 

  • Johnstone RM, Adam M, Hammond JR, Orr L, Turbide C (1987) Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem 262:9412–9420

    CAS  PubMed  Google Scholar 

  • Johnstone RM, Mathew A, Mason AB, Teng K (1991) Exosome formation during maturation of mammalian and avian reticulocytes: evidence that exosome release is a major route for externalization of obsolete membrane proteins. J Cell Physiol 147:27–36

    Article  CAS  PubMed  Google Scholar 

  • Kanwar SS, Dunlay CJ, Simeone DM, Nagrath S (2014) Microfluidic device (ExoChip) for on-chip isolation, quantification and characterization of circulating exosomes. Lab Chip 14:1891–1900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Keller S, Sanderson MP, Stoeck A, Altevogt P (2006) Exosomes: from biogenesis and secretion to biological function. Immunol Lett 107:102–108

    Article  CAS  PubMed  Google Scholar 

  • Kesimer M, Gupta R (2015) Physical characterization and profiling of airway epithelial derived exosomes using light scattering. Methods 87:59–63

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim CH, Lee SG, Kang MJ, Lee S, Choi YW (2017a) Surface modification of lipid-based nanocarriers for cancer cell-specific drug targeting. J Pharm Investig 47:203–227

    Article  CAS  Google Scholar 

  • Kim S, Sohn HJ, Lee HJ, Sohn DH, Hyun SJ, Cho HI, Kim TG (2017b) Use of engineered exosomes expressing HLA and costimulatory molecules to generate antigen-specific CD8 + T cells for adoptive cell therapy. J Immunother 40:83–93

    Article  CAS  PubMed  Google Scholar 

  • Lai A, Elfeky O, Rice GE, Salomon C (2018) Optimized specific isolation of placenta-derived exosomes from maternal circulation. Methods Mol Biol 1710:131–138

    Article  CAS  PubMed  Google Scholar 

  • Lakkaraju A, Rodriguez-Boulan E (2008) Itinerant exosomes: emerging roles in cell and tissue polarity. Trends Cell Biol 18:199–209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lane RE, Korbie D, Anderson W, Vaidyanathan R, Trau M (2015) Analysis of exosome purification methods using a model liposome system and tunable-resistive pulse sensing. Sci Rep 5:7639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lattanzi L, Federico M (2012) A strategy of antigen incorporation into exosomes: comparing cross-presentation levels of antigens delivered by engineered exosomes and by lentiviral virus-like particles. Vaccine 30:7229–7237

    Article  CAS  PubMed  Google Scholar 

  • Li XB, Zhang ZR, Schluesener HJ, Xu SQ (2006) Role of exosomes in immune regulation. J Cell Mol Med 10:364–375

    Article  CAS  PubMed  Google Scholar 

  • Li P, Kaslan M, Lee SH, Yao J, Gao Z (2017) Progress in exosome isolation techniques. Theranostics 7:789–804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liga A, Vliegenthart AD, Oosthuyzen W, Dear JW, Kersaudy-Kerhoas M (2015) Exosome isolation: a microfluidic road-map. Lab Chip 15:2388–2394

    Article  CAS  PubMed  Google Scholar 

  • Lim JY, Kim NA, Lim DG, Kim KH, Choi DH, Jeong SH (2016) Process cycle development of freeze drying for therapeutic proteins with stability evaluation. J Pharm Investig 46:519–536

    Article  CAS  Google Scholar 

  • Luan X, Sansanaphongpricha K, Myers I, Chen H, Yuan H, Sun D (2017) Engineering exosomes as refined biological nanoplatforms for drug delivery. Acta Pharmacol Sin 38:754–763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lyu L, Wang H, Li B, Qin Q, Qi L, Nagarkatti M, Nagarkatti P, Janicki JS, Wang XL, Cui T (2015) A critical role of cardiac fibroblast-derived exosomes in activating renin angiotensin system in cardiomyocytes. J Mol Cell Cardiol 89:268–279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Manfredi F, di Bonito P, Ridolfi B, Anticoli S, Arenaccio C, Chiozzini C, Baz Morelli A, Federico M (2016) The CD8+ T cell-mediated immunity induced by HPV-E6 uploaded in engineered exosomes is improved by ISCOMATRIXTM adjuvant. Vaccines. https://doi.org/10.3390/vaccines4040042

    Article  PubMed  PubMed Central  Google Scholar 

  • Mignot G, Roux S, Thery C, Ségura E, Zitvogel L (2006) Prospects for exosomes in immunotherapy of cancer. J Cell Mol Med 10:376–388

    Article  CAS  PubMed  Google Scholar 

  • Moon PG, Lee JE, You S, Kim TK, Cho JH, Kim IS, Kwon TH, Kim CD, Park SH, Hwang D, Kim YL, Baek MC (2011a) Proteomic analysis of urinary exosomes from patients of early IgA nephropathy and thin basement membrane nephropathy. Proteomics 11:2459–2475

    Article  CAS  PubMed  Google Scholar 

  • Moon PG, You S, Lee JE, Hwang D, Baek MC (2011b) Urinary exosomes and proteomics. Mass Spectrom Rev 30:1185–1202

    Article  CAS  PubMed  Google Scholar 

  • Morelli AE, Larregina AT, Shufesky WJ, Sullivan ML, Stolz DB, Papworth GD, Zahorchak AF, Logar AJ, Wang Z, Watkins SC, Falo LD Jr, Thomson AW (2004) Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells. Blood 104:3257–3266

    Article  CAS  PubMed  Google Scholar 

  • Morishita M, Takahashi Y, Matsumoto A, Nishikawa M, Takakura Y (2016) Exosome-based tumor antigens-adjuvant co-delivery utilizing genetically engineered tumor cell-derived exosomes with immunostimulatory CpG DNA. Biomaterials 111:55–65

    Article  CAS  PubMed  Google Scholar 

  • Munagala R, Aqil F, Jeyabalan J, Gupta RC (2016) Bovine milk-derived exosomes for drug delivery. Cancer Lett 371:48–61

    Article  CAS  PubMed  Google Scholar 

  • Newton W, Kim J, Luo J, Luo L (2017) Stem cell derived exosomes: a novel vector for tissue repair and diabetic therapy. J Mol Endocrinol. https://doi.org/10.1530/JME-17-0080

    Article  PubMed  Google Scholar 

  • Ohno S, Takanashi M, Sudo K, Ueda S, Ishikawa A, Matsuyama N, Fujita K, Mizutani T, Ohgi T, Ochiya T, Gotoh N, Kuroda M (2013) Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol Ther 21:185–191

    Article  CAS  PubMed  Google Scholar 

  • Qazi KR, Torregrosa Paredes P, Dahlberg B, Grunewald J, Eklund A, Gabrielsson S (2010) Proinflammatory exosomes in bronchoalveolar lavage fluid of patients with sarcoidosis. Thorax 65:1016–1024

    Article  PubMed  Google Scholar 

  • Qu Y, Franchi L, Nunez G, Dubyak GR (2007) Nonclassical IL-1 beta secretion stimulated by P2 × 7 receptors is dependent on inflammasome activation and correlated with exosome release in murine macrophages. J Immunol 179:1913–1925

    Article  CAS  PubMed  Google Scholar 

  • Rani S, Ryan AE, Griffin MD, Ritter T (2015) Mesenchymal stem cell-derived extracellular vesicles: toward cell-free therapeutic applications. Mol Ther 23:812–823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ribeiro MF, Zhu H, Millard RW, Fan G-C (2013) Exosomes function in pro-and anti-angiogenesis. Curr Angiogenes 2:54

    CAS  PubMed  PubMed Central  Google Scholar 

  • Saari H, Lazaro-Ibanez E, Viitala T, Vuorimaa-Laukkanen E, Siljander P, Yliperttula M (2015) Microvesicle- and exosome-mediated drug delivery enhances the cytotoxicity of Paclitaxel in autologous prostate cancer cells. J Control Releas 220:727–737

    Article  CAS  Google Scholar 

  • Sabapatha A, Gercel-Taylor C, Taylor DD (2006) Specific isolation of placenta-derived exosomes from the circulation of pregnant women and their immunoregulatory consequences. Am J Reprod Immunol 56:345–355

    Article  CAS  PubMed  Google Scholar 

  • Sato YT, Umezaki K, Sawada S, Mukai SA, Sasaki Y, Harada N, Shiku H, Akiyoshi K (2016) Engineering hybrid exosomes by membrane fusion with liposomes. Sci Rep 6:21933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schorey JS, Bhatnagar S (2008) Exosome function: from tumor immunology to pathogen biology. Traffic 9:871–881

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shao H, Chung J, Lee K, Balaj L, Min C, Carter BS, Hochberg FH, Breakefield XO, Lee H, Weissleder R (2015) Chip-based analysis of exosomal mRNA mediating drug resistance in glioblastoma. Nat Commun 6:6999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sharma S, Rasool HI, Palanisamy V, Mathisen C, Schmidt M, Wong DT, Gimzewski JK (2010) Structural-mechanical characterization of nanoparticle exosomes in human saliva, using correlative AFM, FESEM, and force spectroscopy. ACS Nano 4:1921–1926

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sheldon H, Heikamp E, Turley H, Dragovic R, Thomas P, Oon CE, Leek R, Edelmann M, Kessler B, Sainson RC (2010) New mechanism for Notch signaling to endothelium at a distance by Delta-like 4 incorporation into exosomes. Blood 116:2385–2394

    Article  CAS  PubMed  Google Scholar 

  • Sheridan C (2016) Exosome cancer diagnostic reaches market. Nat Biotechnol 34:359–360

    Article  CAS  PubMed  Google Scholar 

  • Shin S, Han D, Park MC, Mun JY, Choi J, Chun H, Kim S, Hong JW (2017) Separation of extracellular nanovesicles and apoptotic bodies from cancer cell culture broth using tunable microfluidic systems. Sci Rep 7:9907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shtam TA, Kovalev RA, Varfolomeeva EY, Makarov EM, Kil YV, Filatov MV (2013) Exosomes are natural carriers of exogenous siRNA to human cells in vitro. Cell Commun Signal 11:88

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simeoli R, Montague K, Jones HR, Castaldi L, Chambers D, Kelleher JH, Vacca V, Pitcher T, Grist J, Al-Ahdal H, Wong LF, Perretti M, Lai J, Mouritzen P, Heppenstall P, Malcangio M (2017) Exosomal cargo including microRNA regulates sensory neuron to macrophage communication after nerve trauma. Nat Commun 8:1778

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith JA, Ng KS, Mead BE, Dopson S, Reeve B, Edwards J, Wood MJA, Carr AJ, Bure K, Karp JM, Brindley DA (2015) Extracellular vesicles: commercial potential as byproducts of cell manufacturing for research and therapeutic use. Bioprocess Int. http://www.bioprocessintl.com/manufacturing/cell-therapies/extracellularvesicles-commercial-potential-as-byproducts-of-cell-manufacturing-for-research-and-therapeutic-use. Accessed 14 April 2015

  • Song JG, Lee SH, Han H-K (2017) The stabilization of biopharmaceuticals: current understanding and future perspectives. J Pharm Investig 47:475–496

    Article  CAS  Google Scholar 

  • Sun D, Zhuang X, Xiang X, Liu Y, Zhang S, Liu C, Barnes S, Grizzle W, Miller D, Zhang HG (2010) A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes. Mol Ther 18:1606–1614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tatischeff I, Larquet E, Falcon-Perez JM, Turpin PY, Kruglik SG (2012) Fast characterisation of cell-derived extracellular vesicles by nanoparticles tracking analysis, cryo-electron microscopy, and Raman tweezers microspectroscopy. J Extracell Vesicles 1

  • Tauro BJ, Greening DW, Mathias RA, Ji H, Mathivanan S, Scott AM, Simpson RJ (2012) Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes. Methods 56:293–304

    Article  CAS  PubMed  Google Scholar 

  • Thery C, Regnault A, Garin J, Wolfers J, Zitvogel L, Ricciardi-Castagnoli P, Raposo G, Amigorena S (1999) Molecular characterization of dendritic cell-derived exosomes. Selective accumulation of the heat shock protein hsc73. J Cell Biol 147:599–610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thery C, Amigorena S, Raposo G, Clayton A (2006) Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol Chap 3:Unit 3 22

    Google Scholar 

  • Tian Y, Li S, Song J, Ji T, Zhu M, Anderson GJ, Wei J, Nie G (2014) A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Biomaterials 35:2383–2390

    Article  CAS  PubMed  Google Scholar 

  • Tibbitt MW, Dahlman JE, Langer R (2016) Emerging frontiers in drug delivery. J Am Chem Soc 138:704–717

    Article  CAS  PubMed  Google Scholar 

  • van Niel G, Raposo G, Candalh C, Boussac M, Hershberg R, Cerf-Bensussan N, Heyman M (2001) Intestinal epithelial cells secrete exosome-like vesicles. Gastroenterology 121:337–349

    Article  PubMed  Google Scholar 

  • van Niel G, Porto-Carreiro I, Simoes S, Raposo G (2006) Exosomes: a common pathway for a specialized function. J Biochem 140:13–21

    Article  CAS  PubMed  Google Scholar 

  • van der Pol E, Hoekstra AG, Sturk A, Otto C, van Leeuwen TG, Nieuwland R (2010) Optical and non-optical methods for detection and characterization of microparticles and exosomes. J Thromb Haemost 8:2596–2607

    Article  PubMed  Google Scholar 

  • van der Pol E, Boing AN, Harrison P, Sturk A, Nieuwland R (2012) Classification, functions, and clinical relevance of extracellular vesicles. Pharmacol Rev 64:676–705

    Article  CAS  PubMed  Google Scholar 

  • Vlassov AV, Magdaleno S, Setterquist R, Conrad R (2012) Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochimica et Biophysica Acta (BBA) Gen Subj 1820:940–948

    Article  CAS  Google Scholar 

  • Wahlgren J, De LKT, Brisslert M, Vaziri Sani F, Telemo E, Sunnerhagen P, Valadi H (2012) Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes. Nucl Acids Res 40:e130

    Article  CAS  PubMed  Google Scholar 

  • Wan Y, Cheng G, Liu X, Hao SJ, Nisic M, Zhu CD, Xia YQ, Li WQ, Wang ZG, Zhang WL, Rice SJ, Sebastian A, Albert I, Belani CP, Zheng SY (2017) Rapid magnetic isolation of extracellular vesicles via lipid-based nanoprobes. Nat Biomed Eng. https://doi.org/10.1038/s41551-017-0058

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang Y, Zhang L, Li Y, Chen L, Wang X, Guo W, Zhang X, Qin G, He SH, Zimmerman A, Liu Y, Kim IM, Weintraub NL, Tang Y (2015) Exosomes/microvesicles from induced pluripotent stem cells deliver cardioprotective miRNAs and prevent cardiomyocyte apoptosis in the ischemic myocardium. Int J Cardiol 192:61–69

    Article  PubMed  PubMed Central  Google Scholar 

  • Whitford W, Ludlow JW, Cadwell JJ (2015) Continuous production of exosomes: utilizing the technical advantages of hollow-fiber bioreactor technology. Genet Eng Biotechnol News 35:34

    Article  Google Scholar 

  • Wiklander OP, Nordin JZ, O’Loughlin A, Gustafsson Y, Corso G, Mager I, Vader P, Lee Y, Sork H, Seow Y, Heldring N, Alvarez-Erviti L, Smith CI, Le Blanc K, Macchiarini P, Jungebluth P, Wood MJ, Andaloussi SE (2015) Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting. J Extracell Vesicles 4:26316

    Article  PubMed  Google Scholar 

  • Witwer KW, Buzas EI, Bemis LT, Bora A, Lässer C, Lötvall J, Nolte-′t Hoen EN, Piper MG, Sivaraman S, Skog J, Théry C, Wauben MH, Hochberg F (2013) Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J Extracell Vesicles. https://doi.org/10.3402/jev.v2i0.20360

    Article  PubMed  PubMed Central  Google Scholar 

  • Wu M, Ouyang Y, Wang Z, Zhang R, Huang PH, Chen C, Li H, Li P, Quinn D, Dao M, Suresh S, Sadovsky Y, Huang TJ (2017) Isolation of exosomes from whole blood by integrating acoustics and microfluidics. Proc Natl Acad Sci USA 114:10584–10589

    Article  CAS  PubMed  Google Scholar 

  • Xie Y, Bai O, Zhang H, Li W, Xiang J (2010a) Tumor necrosis factor gene-engineered J558 tumor cell-released exosomes stimulate tumor antigen P1A-specific CD8 + CTL responses and antitumor immunity. Cancer Biother Radiopharm 25:21–28

    Article  CAS  PubMed  Google Scholar 

  • Xie Y, Bai O, Zhang H, Yuan J, Zong S, Chibbar R, Slattery K, Qureshi M, Wei Y, Deng Y, Xiang J (2010b) Membrane-bound HSP70-engineered myeloma cell-derived exosomes stimulate more efficient CD8(+) CTL- and NK-mediated antitumour immunity than exosomes released from heat-shocked tumour cells expressing cytoplasmic HSP70. J Cell Mol Med 14:2655–2666

    Article  CAS  PubMed  Google Scholar 

  • Xu R, Greening DW, Zhu HJ, Takahashi N, Simpson RJ (2016) Extracellular vesicle isolation and characterization: toward clinical application. J Clin Invest 126:1152–1162

    Article  PubMed  PubMed Central  Google Scholar 

  • Xu J-Y, Chen G-H, Yang Y-J (2017) Exosomes: a rising star in failing hearts. Front Physiol 8:494

    Article  PubMed  PubMed Central  Google Scholar 

  • Yang T, Martin P, Fogarty B, Brown A, Schurman K, Phipps R, Yin VP, Lockman P, Bai S (2015) Exosome delivered anticancer drugs across the blood-brain barrier for brain cancer therapy in Danio rerio. Pharm Res 32:2003–2014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang Y, Hong Y, Nam GH, Chung JH, Koh E, Kim IS (2017) Virus-mimetic fusogenic exosomes for direct delivery of integral membrane proteins to target cell membranes. Adv Mater 29

  • Yim N, Ryu SW, Choi K, Lee KR, Lee S, Choi H, Kim J, Shaker MR, Sun W, Park JH, Kim D, Heo WD, Choi C (2016) Exosome engineering for efficient intracellular delivery of soluble proteins using optically reversible protein-protein interaction module. Nat Commun 7:12277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zarovni N, Corrado A, Guazzi P, Zocco D, Lari E, Radano G, Muhhina J, Fondelli C, Gavrilova J, Chiesi A (2015) Integrated isolation and quantitative analysis of exosome shuttled proteins and nucleic acids using immunocapture approaches. Methods 87:46–58

    Article  CAS  PubMed  Google Scholar 

  • Zeringer E, Barta T, Li M, Vlassov AV (2015) Strategies for isolation of exosomes. Cold Spring Harb Protoc 2015: 319–323

  • Zitvogel L, Regnault A, Lozier A, Wolfers J, Flament C, Tenza D, Ricciardi-Castagnoli P, Raposo G, Amigorena S (1998) Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell derived exosomes. Nat Med 4:594–600

    Article  CAS  PubMed  Google Scholar 

  • Zou G, Benktander JD, Gizaw ST, Gaunitz S, Novotny MV (2017) Comprehensive analytical approach toward glycomic characterization and profiling in urinary exosomes. Anal Chem 89:5364–5372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study was supported by the Basic Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (NRF-2014R1A1A2057483).

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Correspondence to Seung Rim Hwang.

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All authors (S. Manandhar, V. K. Kothandan, J. Oh, S.H. Yoo, J. Hwang, S.R. Hwang) declare that they have no conflict of interest.

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Manandhar, S., Kothandan, V.K., Oh, J. et al. A pharmaceutical investigation into exosomes. J. Pharm. Investig. 48, 617–626 (2018). https://doi.org/10.1007/s40005-018-0391-7

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  • DOI: https://doi.org/10.1007/s40005-018-0391-7

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