Recent advancements in the use of exosomes as drug delivery systems

Edwin J. Bunggulawa1, Wei Wang1, Tieying Yin1, Nan Wang2, Colm Durkan2, Shaobin Wang1, Guixue Wang1
1Key Laboratory of Biorheological Science and Technology, Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, College of Bioengineering, Chongqing University, No 174 Shazheng Street, Shapingba District, Chongqing, 400044, People’s Republic of China
2Nanoscience Centre, Department of Engineering, University of Cambridge, JJ Thomson Avenue, Cambridge, CB3 0FF, UK

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Rufino-Ramos D, Albuquerque PR, Carmona V, Perfeito R, Nobre RJ, Parera de Almeida L. Extracellular vesicles: novel promising delivery systems for therapy of brain diseases. J Control Release. 2017;262:247–58.

Braccioli L, Van Velthoven C, Heijnen CJ. Exosomes: a new weapon to treat the central nervous system. Mol Neurobiol. 2014;49:113–9.

Yuan D, Zhao Y, Banks WA, Bullock KM, Haney M, Batrakova E, Kabanov AV. Macrophage exosomes as natural nanocarriers for protein delivery to inflamed brain. Biomaterials. 2017;142:1.

Zhou Y, Tian T, Zhu Y, Jaffar AD, Hu F, Qi Y, Sun B, Xiao Z. Exosomes transfer among different species cells and mediating miRNAs delivery. J Cell Biochem. 2017;118:4267–74.

Schorey JS, Harding CV. Extracellular vesicles and infectious diseases: new complexity to an old story. J Clin Invest. 2016;126:1181–9.

Alenquer M, Amorim MJ. Exosome biogenesis, regulation, and function in viral infection. Viruses. 2015;7:5066–83.

Hessvik NP, Llorente A. Current knowledge on exosome biogenesis and release. Cell Mol Life Sci. 2018;75:193–208.

Beach A, Zhang HG, Ratajczak MZ, Kakar SS. Exosomes: an overview of biogenesis, composition and role in ovarian cancer. J Ovarian Res. 2014;7:14. https://doi.org/10.1186/1757-2215-7-14 .

Barile L, Vassalli G. Exosomes: therapy delivery tools and biomarkers of diseases. Pharmacol Ther. 2017;174:63–78.

Li W, Li C, Zhou T, Liu X, Liu X, Li X, Chen D. Role of exosomal proteins in cancer diagnosis. Mol Cancer. 2017;16:145. https://doi.org/10.1186/s12943-017-0706-8 .

Zhang H, Freitas D, Kim HS, Fabijanic K, Li Z, Chen H, Mark MT, Molina H, Martin AB, Bojmar L, Fang J, Rampersaud S, Hoshino A, Matei I, Kenific CM, Nakajima M, Mutvei AP, Sansone P, Buehring W, Wang H, Jimenez JP, Cohen-Gould L, Paknejad N, Brendel M, Manova-Todorova K, Magalhaes A, Ferriera JA, Osorio H, Silva AM, Massey A, Cubillos-Ruiz JR, Galletti G, Giannakakou P, Cuervo AM, Blenis J, Schwartz R, Brady MS, Peinado H, Bromberg J, Matsui H, Reis CA, Lyden D. Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation. Nat Cell Biol. 2018;20:332–43.

Mckelvey KJ, Powell KL, Ashton AW, Morris JM, Mccracken SA. Exosomes: mechanisms of uptake. J Circ Biomarkers. 2015;4:1.

He C, Zheng S, Luo Y, Wang B. Exosome theranostics: biology and translational medicine. Theranostics. 2018;8:237–55.

Corliss BA, Azimi MS, Munson J, Peirce SM, Murfee WL. Macrophages: an inflammatory link between angiogenesis and lymphangiogenesis. Microcirculation. 2016;23:95–121.

Malyshev I, Malyshev Y. Current concept and update of the macrophage plasticity concept: intracellular mechanisms of reprogramming and M3 macrophage “switch” phenotype. Biomed Res Int. 2015;2015:341308. https://doi.org/10.1155/2015/341308 .

Wang C, Zhang C, Liu L, Xi A, Chen B, Li Y, Du J. Macrophage-derived mir-155-containing exosomes suppress fibroblast proliferation and promote fibroblast inflammation during cardiac injury. Mol Ther. 2017;25:192–204.

Monti E, Fanzani A. Uncovering metabolism in rhabdomyosarcoma. Cell Cycle. 2015;15:184–95.

Poniewierska-Baran A, Schneider G, Sun W, Abdelbaset-Ismail A, Barr FG, Ratajczak MZ. Human rhabdomyosarcoma cells express functional pituitary and gonadal sex hormone receptors: therapeutic implications. Int J Oncol. 2016;48:1815–24.

Ghayad SE, Rammal G, Ghamloush F, Basma H, Nasr R, Diab-Assaf M, Chelala C, Saab R. Exosomes derived from embryonal and alveolar rhabdomyosarcoma carry differential miRNA cargo and promote invasion of recipient fibroblasts. Sci Rep. 2016;6:37088.

Sung BH, Weaver AM. Exosome secretion promotes chemotaxis of cancer cells. Cell Adhes Migr. 2017;11:187–95.

Schillaci O, Fontana S, Monteleone F, Taverna S, Di Bella MA, Di Vigio D, Alessandro R. Exosomes from metastatic cancer cells transfer amoeboid phenotype to non-metastatic cells and increase endothelial permeability: their emerging role in tumor heterogeneity. Sci Rep. 2017;7:4711. https://doi.org/10.1038/s41598-017-05002-y .

Kalluri R. The biology and function of exosomes in cancer. J Clin Invest. 2016;126:1208–15.

Nabavi N, Bennewith KL, Churg A, Wang Y, Collins CC, Mutti L. Switching off malignant mesothelioma: exploiting the hypoxic microenvironment. Genes Cancer. 2016;7:340–54.

Kalra N, Zhang J, Thomas A, Xi L, Cheung M, Talarchek J, Burkett S, Tsokos MG, Chen Y, Raffeld M, Miettinen M, Pastan I, Testa JR, Hassan P. Mesothelioma patient derived tumor xenografts with defined BAP1 mutations that mimic the molecular characteristics of human malignant mesothelioma. BMC Cancer. 2015;15:1–378. https://doi.org/10.1186/s12885-015-1362-2 .

Greening DW, Ji H, Chen M, Robinson BW, Dick IM, Creaney J, Simpson RJ. Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo. Sci Rep. 2016;6:32643. https://doi.org/10.1038/srep32643 .

Abdelmagid SM, Sondag GR, Moussa FM, Belcher JY, Yu B, Stinnett H, Novak K, Mbimba T, Khol M, Hankenson KD, Malcuit C, Safadi FF. Mutation in osteoactivin promotes receptor activator of NFκB ligand (RANKL)-mediated osteoclast differentiation and survival but inhibits osteoclast function. J Biol Chem. 2015;290:20128–46.

Charles JF, Aliprantis AO. Osteoclasts: more than ‘bone eaters’. Trends Mol Med. 2014;20:449–59.

Sun W, Zhao C, Li Y, Wang L, Nie G, Peng J, Wang A, Zhang P, Tian W, Li Q, Song J, Wang C, Xu X, Zhao D, Xu Z, Zhong G, Han B, Ling S, Chang YZ, Li Y. Osteoclast-derived microRNA-containing exosomes selectively inhibit osteoblast activity. Cell Discov. 2016;2:16015.

Klein AP. Genetic susceptibility to pancreatic cancer. Mol Carcinog. 2012;51:14–24.

Neesse A, Michl P, Frese KK, Feig C, Cook N, Jacobetz MA, Lolkema MP, Buchholz M, Olive KP, Gress TM. Stromal biology and therapy in pancreatic cancer. Gut. 2011;60:861.

Masamune A, Yoshida N, Hamada S, Takikawa T, Nabeshima T, Shimosegawa T. Exosomes derived from pancreatic cancer cells induce activation and profibrogenic activities in pancreatic stellate cells. Biochem Biophys Res Commun. 2017;495:71–7.

Swonger JM, Liu JS, Ivey MJ, Tallquist MD. Genetic tools for identifying and manipulating fibroblasts in the mouse. Differentiation. 2016;92:66–83.

James AJ, Penrose JF, Cazaly AM, Holgate ST, Sampson AP. Human bronchial fibroblasts express the 5-lipoxygenase pathway. Respir Res. 2006;7:102. https://doi.org/10.1186/1465-9921-7-102 .

Haj-Salem I, Plante S, Gounni AS, Rouabhia M, Chakir J. Fibroblast-derived exosomes promote epithelial cell proliferation through TGF-β2 signaling pathway in severe asthma. Allergy. 2018;1416:55–87.

White IA, Sanina C, Balkan W, Hare JM. Mesenchymal stem cells in cardiology. Methods Mol Biol. 2016;1416:55.

Samsonraj RM, Raghunath M, Nurcombe V, Hui JH, Van Wijnen AJ, Cool SM. Concise review: multifaceted characterization of human mesenchymal stem cells for use in regenerative medicine. Stem Cells Transl Med. 2017;6:2173–85.

Lou G, Chen Z, Zheng M, Liu Y. Mesenchymal stem cell-derived exosomes as a new therapeutic strategy for liver diseases. Exp Mol Med. 2017;49:e346. https://doi.org/10.1038/emm.2017.63 .

Pedersen KW, Kierulf B, Manger I, Oksvold MP, Li M, Vlassov A, Roos N, Kullmann A, Neurauter A. Direct isolation of exosomes from cell culture: simplifying methods for exosome enrlchment and analysis. Transl Biomed. 2015;6:2. https://doi.org/10.21767/2172-0479.100018 .

Livshts MA, Khomyakova E, Evtushenko EG, Lazarev VN, Kulemin NA, Semina SE, Generozov EV, Govorun VM. Isolation of exosomes by differential centrifugation: theoretical analysis of a commonly used protocol. Sci Rep. 2015;5:21447.

Helwa I, Cai J, Drewry MD, Zimmerman A, Dinkins MB, Khaled ML, Seremwe M, Dismuke WM, Bieberich E, Stamer WD, Hamrick MW, Liu Y. A comparative study of serum exosome isolation using differential ultracentrifugation and three commercial reagents. PLoS ONE. 2017;12:e0170628. https://doi.org/10.1371/journal.pone.0170628 .

Yakimchuk K. Exosomes: isolation and characterization methods and specific markers. Maker Methods. 2015;5:1450. https://doi.org/10.13070/mm.en.5.1450 .

Kang H, Kim J, Park J. Methods to isolate extracellular vesicles for diagnosis. Micro Nano Syst Lett. 2017;5:15. https://doi.org/10.1186/s40486-017-0049-7 .

Contreras-Naranjo JC, Wu HJ, Ugaz VM. Microfluidics for exosome isolation and analysis: enabling liquid biopsy for personalized medicine. Lab Chip. 2017;17:3558–77.

Taylor DD, Shah S. Methods of isolating extracellular vesicles impact down-stream analyses of their cargoes. Methods. 2015;87:3–10.

Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th ed. New York: National Center for Biotechnology Informationõs Bookshelf; 2002. p. 93–126.

Vekey K, Telekes A, Vertes A. Preface—medical applications of mass spectrometry. Medical applications of mass spectrometry, vol. 18. 2008:1262–71.

Kotmakçı M, Akbaba GE. Exosome isolation: is there an optimal method with regard to diagnosis or treatment?, chap 8. In: Wang J, editor. Novel implication of exosome in diagnosis and treatment of cancer and infection disease. London: Intech; 2017. p. 163–82.

Deregibus MC, Figliolini F, D’Antico S, Manzini PM, Pasquino C, De Lena MD, Tetta C, Brizzi MF, Camussi G. Charge-based precipitation of extracellular vesicles. Int J Mol Med. 2016;38:1359–66.

Oksvold MP, Neurauter A, Pedersen KW. Magnetic bead-based isolation of exosomes. Methods Mol Biol. 2015;1218:465–81.

Li P, Kaslan M, Lee SH, Yao J, Gao Z. Progress in exosome isolation techniques. Theranostics. 2017;7:789.

Aryani A, Denecke B. Exosomes as a nanodelivery system: a key to the future of neuromedicine? Mol Neurobiol. 2016;53:818–34.

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;6:287–96.

Jiang XC, Gao JQ. Exosomes as novel bio-carriers for gene and drug delivery. Int J Pharm. 2017;521:167–75.

Van der Meel R, Fens MH, Vader P, van Solinge WW, Eniola-Adefeso O, Schiffelers RM. Extracellular vesicles as drug delivery systems: lessons from the liposome field. J Control Release. 2014;195:72–85.

Johnsen KB, Gudbergsson JM, Skov MN, 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;1846:75–87.

Zhuang X, Xiang X, Grizzle W, Sun D, Zhang S, Axtell RC, Ju S, Mu J, Zhang L, Steinman L. Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol Ther. 2011;19:1769.

Batrakova EV, Kim MS. Using exosomes, naturally-equipped nanocarriers, for drug delivery. J Control Release. 2015;219:396–405.

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

Liu Y, Li D, Liu Z, Zhou Y, Chu D, Li X, Jiang X, Hou D, Chen X, Chen Y. Targeted exosome-mediated delivery of opioid receptor Mu siRNA for the treatment of morphine relapse. Sci Rep. 2015;5:17543.

Sun D, Zhuang X, Xiang X, Liu Y, Zhang S, Liu C, Barnes S, Grizzle W, Miller D, Zhang HG. A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes. Mol Ther. 2010;18:1606–14.

Hood JL, Scott MJ, Wickline SA. Maximizing exosome colloidal stability following electroporation. Anal Biochem. 2014;448:41–9.

Saari H, Lázaroibáñez E, Viitala T, Vuorimaalaukkanen E, Siljander P, Yliperttula M. Microvesicle- and exosome-mediated drug delivery enhances the cytotoxicity of paclitaxel in autologous prostate cancer cells. J Control Release. 2015;220:727–37.

Kim MS, Haney MJ, Zhao Y, Mahajan V, Deygen I, Klyachko NL, Inskoe E, Piroyan A, Sokolsky M, Okolie O, Hingtgen SD, Karbanov AV, Batrakova EV. Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomedicine. 2016;12:655–64.

Tian Y, Li S, Song J, Ji T, Zhu M, Anderson GJ, Wei J, Nie G. A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Biomaterials. 2014;35:2383–90.

Agrawal AK, Aqil F, Jeyabalan J, Spencer WA, Beck J, Gachuki BW, Alhakeem SS, Oben K, Munagala R, Bondada S, Gupta RC. Milk-derived exosomes for oral delivery of paclitaxel. Nanomedicine. 2017;13:1627–36.

Lamichhane TN, Raiker RS, Jay SM. Exogenous DNA loading into extracellular vesicles via electroporation is size-dependent and enables limited gene delivery. Mol Pharm. 2015;12:3650–7.

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;38:754–63.

Wei JG, Zou S, Wei YO, Torta F, Alexandra AF, Schiffelers RM, Storm G, Wang JW, Czarny B, Pastorin G. Bioinspired cell-derived nanovesicles versus exosomes as drug delivery systems: a cost-effective alternative. Sci Rep. 2017;7:14322. https://doi.org/10.1038/s41598-017-14725-x .

Wang J, Gan Y, Han P, Yin J, Liu Q, Ghanian S, Gao F, Gong G, Tang Z. Ischemia-induced Neuronal Cell Death Is Mediated by Chemokine Receptor CX3CR1. Sci Rep. 2018;8:556. https://doi.org/10.1038/s41598-017-18774-0 .

Tian T, Zhang HX, He CP, Fan S, Zhu YL, Qi C, Huang NP, Xiao ZD, Lu ZH, Tannous BA, Gao J. Surface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy. Biomaterials. 2018;150:137–49.

Kobayashi S, Nakase I, Kawabata N, Yu HH, Pujals S, Imanishi M, Giralt E, Futaki S. Cytosolic targeting of macromolecules using a pH-dependent fusogenic peptide in combination with cationic liposomes. Bioconjug Chem. 2009;20:953–9.

Sakurai F, Nishioka T, Saito H, Baba T, Okuda A, Matsumoto O, Taga T, Yamashita F, Takakura Y, Hashida M. Interaction between DNA-cationic liposome complexes and erythrocytes is an important factor in systemic gene transfer via the intravenous route in mice: the role of the neutral helper lipid. Gene Ther. 2001;8:677–86.

Nakase I, Futaki S. Combined treatment with a pH-sensitive fusogenic peptide and cationic lipids achieves enhanced cytosolic delivery of exosomes. Sci Rep. 2015;5:10112. https://doi.org/10.1038/srep10112 .

Liu R, Wang X, Curtiss C, Landas S, Rong R, Sheikh MS, Huang Y. Monoglyceride lipase gene knockout in mice leads to increased incidence of lung adenocarcinoma. Cell Death & Dis. 2018;9:36. https://doi.org/10.1038/s41419-017-0188-z .

Kim MS, Haney MJ, Zhao Y, Yuan D, Deygen I, Klyachko NL, Kabanov AV, Batrakova EV. Engineering macrophage-derived exosomes for targeted paclitaxel delivery to pulmonary metastases: in vitro and in vivo evaluations. Nanomedicine. 2018;14:195–204.

Bozzuto G, Molinari A. Liposomes as nanomedical devices. Int J Nanomed. 2015;10:975–99.

Dimov N, Kastner E, Hussain M, Perrie Y, Szita N. Formation and purification of tailored liposomes for drug delivery using a module-based micro continuous-flow system. Sci Rep. 2017;7:12045. https://doi.org/10.1038/s41598-017-11533-1 .

Sato YT, Umezaki K, Sawada S, Mukai S, Sasaki Y, Harada N, Shiku H, Akiyoshi K. Engineering hybrid exosomes by membrane fusion with liposomes. Sci Rep. 2016;6:21933. https://doi.org/10.1038/srep21933 .

Zhou Z, Xing X, Tian C, Wei W, Li D, Hu F, Du S. A multifunctional nanocage-based MOF with tri- and tetranuclear zinc cluster secondary building units. Sci Rep. 2018;8:3117. https://doi.org/10.1038/s41598-018-21382-1 .

Liu R, Yu T, Shi Z, Wang Z. The preparation of metal-organic frameworks and their biomedical application. Int J Nanomed. 2016;11:1187–200.

Della Rocca J, Liu D, Lin W. Nanoscale metal–organic frameworks for biomedical imaging and drug delivery. Acc Chem Res. 2011;44:957–68.

Al Haydar M, Abid HR, Sunderland B, Wang S. Metal organic frameworks as a drug delivery system for flurbiprofen. Drug Des Dev Ther. 2017;11:2685–95.

Illes B, Hirschle P, Barnert S, Cauda V, Wuttke S, Engelke H. Exosome-coated metal-organic framework nanoparticles: an efficient drug delivery platform. Chem Mater. 2017;29:8042–6.