{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T19:28:53Z","timestamp":1776713333542,"version":"3.51.2"},"reference-count":144,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T00:00:00Z","timestamp":1633651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PD\/BD\/135046\/2017"],"award-info":[{"award-number":["PD\/BD\/135046\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/BIA-BQM\/5027\/2020"],"award-info":[{"award-number":["PTDC\/BIA-BQM\/5027\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["DL 57\/2016\/CP1451\/CT0023"],"award-info":[{"award-number":["DL 57\/2016\/CP1451\/CT0023"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Brain metastases (BM) are a frequent complication in patients with advanced stages of cancer, associated with impairment of the neurological function, quality of life, prognosis, and survival. BM treatment consists of a combination of the available cancer therapies, such as surgery, radiotherapy, chemotherapy, immunotherapy and targeted therapies. Even so, cancer patients with BM are still linked to poor prognosis, with overall survival being reported as 12 months or less. Intercellular communication has a pivotal role in the development of metastases, therefore, it has been extensively studied not only to better understand the metastization process, but also to further develop new therapeutic strategies. Exosomes have emerged as key players in intercellular communication being potential therapeutic targets, drug delivery systems (DDS) or biomarkers. In this Review, we focus on the role of these extracellular vesicles (EVs) in BM formation and their promising application in the development of new BM therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ijms221910899","type":"journal-article","created":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T21:23:25Z","timestamp":1633901005000},"page":"10899","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Exosomes and Brain Metastases: A Review on Their Role and Potential Applications"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8816-9932","authenticated-orcid":false,"given":"Filipa D.","family":"Oliveira","sequence":"first","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7891-7562","authenticated-orcid":false,"given":"Miguel A. R. B.","family":"Castanho","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2989-7208","authenticated-orcid":false,"given":"Vera","family":"Neves","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,8]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2021, June 09). Cancer. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/cancer."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Proescholdt, M.A., Sch\u00f6del, P., Doenitz, C., Pukrop, T., H\u00f6hne, J., Schmidt, N.O., and Schebesch, K.-M. (2021). The management of brain metastases\u2014Systematic review of neurosurgical aspects. Cancers, 13.","DOI":"10.3390\/cancers13071616"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1080\/14737140.2021.1851200","article-title":"Brain metastases in metastatic cancer: A review of recent advances in systemic therapies","volume":"21","author":"Steindl","year":"2021","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/s41571-019-0320-3","article-title":"Current approaches to the management of brain metastases","volume":"17","author":"Suh","year":"2020","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_5","first-page":"1","article-title":"Brain metastases","volume":"5","author":"Achrol","year":"2019","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/B978-0-12-811161-1.00001-3","article-title":"Overview of metastatic disease of the central nervous system","volume":"149","author":"Nolan","year":"2018","journal-title":"Handb. Clin. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Elliott, R.O., and He, M. (2021). Unlocking the power of exosomes for crossing biological barriers in drug delivery. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13010122"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s10555-013-9441-9","article-title":"Exosomes in cancer development, metastasis, and drug resistance: A comprehensive review","volume":"32","author":"Azmi","year":"2013","journal-title":"Cancer Metastasis Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.devcel.2019.04.011","article-title":"Exosome-mediated metastasis: Communication from a distance","volume":"49","author":"Wortzel","year":"2019","journal-title":"Dev. Cell"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Weston, W.W., Ganey, T., and Temple, H.T. (2019). The relationship between exosomes and cancer: Implications for diagnostics and therapeutics. BioDrugs.","DOI":"10.1007\/s40259-019-00338-5"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm.2017.125","article-title":"Shedding light on the cell biology of extracellular vesicles","volume":"19","author":"Raposo","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41556-018-0250-9","article-title":"Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication","volume":"21","author":"Mathieu","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/s41556-018-0040-4","article-title":"Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation","volume":"20","author":"Zhang","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.plipres.2017.03.001","article-title":"Lipids in exosomes: Current knowledge and the way forward","volume":"66","author":"Skotland","year":"2017","journal-title":"Prog. Lipid Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1172\/JCI81135","article-title":"The biology and function of exosomes in cancer","volume":"126","author":"Kalluri","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.jmb.2015.09.019","article-title":"ExoCarta: A web-based compendium of exosomal cargo","volume":"428","author":"Keerthikumar","year":"2016","journal-title":"J. Mol. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1083\/jcb.97.2.329","article-title":"Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes","volume":"97","author":"Harding","year":"1983","journal-title":"J. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1083\/jcb.101.3.942","article-title":"Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes","volume":"101","author":"Pan","year":"1985","journal-title":"J. Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/s00109-013-1020-6","article-title":"Exosomes in tumor microenvironment influence cancer progression and metastasis","volume":"91","author":"Kahlert","year":"2013","journal-title":"J. Mol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1083\/jcb.201212113","article-title":"Exosomes: Looking back three decades and into the future","volume":"200","author":"Harding","year":"2013","journal-title":"J. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1083\/jcb.201211138","article-title":"Extracellular vesicles: Exosomes, microvesicles, and friends","volume":"200","author":"Raposo","year":"2013","journal-title":"J. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1021\/acs.molpharmaceut.8b00985","article-title":"Cluster of differentiation 46 is the major receptor in human blood-brain barrier endothelial cells for uptake of exosomes derived from brain-metastatic melanoma cells (SK-Mel-28)","volume":"16","author":"Kuroda","year":"2019","journal-title":"Mol. Pharm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1111\/j.1600-0854.2010.01041.x","article-title":"Cellular internalization of exosomes occurs through phagocytosis","volume":"11","author":"Feng","year":"2010","journal-title":"Traffic"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s10585-017-9857-7","article-title":"The role of the neural niche in brain metastasis","volume":"34","author":"Hoshide","year":"2017","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5049","DOI":"10.1096\/fj.201700254R","article-title":"Astrocytes from the brain microenvironment alter migration and morphology of metastatic breast cancer cells","volume":"31","author":"Shumakovich","year":"2017","journal-title":"FASEB J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1038\/nm.3394","article-title":"Microenvironmental regulation of tumor progression and metastasis","volume":"19","author":"Quail","year":"2013","journal-title":"Nat. Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Conigliaro, A., and Cicchini, C. (2019). Exosome-mediated signaling in epithelial to mesenchymal transition and tumor progression. J. Clin. Med., 8.","DOI":"10.3390\/jcm8010026"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Roma-Rodrigues, C., Fernandes, A.R., and Baptista, P.V. (2014). Exosome in tumour microenvironment: Overview of the crosstalk between normal and cancer cells. Biomed Res. Int., 2014.","DOI":"10.1155\/2014\/179486"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.tips.2016.04.006","article-title":"Exosome-Mediated Metastasis: From Epithelial-Mesenchymal Transition to Escape from Immunosurveillance","volume":"37","author":"Syn","year":"2016","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Steinbichler, T.B., Dud\u00e1s, J., and Riechelmann, H. (2017). The role of exosomes in cancer metastasis. Semin. Cancer Biol.","DOI":"10.1016\/j.semcancer.2017.02.006"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"219","DOI":"10.3892\/or.2012.2111","article-title":"Transforming growth factor-\u03b2 1 enhances the invasiveness of breast cancer cells by inducing a Smad2-dependent epithelial-to-mesenchymal transition","volume":"29","author":"Lv","year":"2013","journal-title":"Oncol. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3645","DOI":"10.1158\/0008-5472.CAN-07-2938","article-title":"Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways","volume":"68","author":"Onder","year":"2008","journal-title":"Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2194","DOI":"10.1016\/j.biocel.2012.08.018","article-title":"Native type IV collagen induces an epithelial to mesenchymal transition-like process in mammary epithelial cells MCF10A","volume":"44","author":"Salazar","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"20318","DOI":"10.1073\/pnas.0910962106","article-title":"Induction of a MT1-MMP and MT2-MMP-dependent basement membrane transmigration program in cancer cells by Snail1","volume":"106","author":"Ota","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.bbcan.2017.03.004","article-title":"Brain metastasization of breast cancer","volume":"1868","author":"Videira","year":"2017","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-19339-5","article-title":"Exosome-mediated breast cancer chemoresistance via miR-155 transfer","volume":"8","author":"Santos","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1093\/carcin\/bgv081","article-title":"Hepatocellular carcinoma-derived exosomes promote motility of immortalized hepatocyte through transfer of oncogenic proteins and RNAs","volume":"36","author":"He","year":"2015","journal-title":"Carcinogenesis"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6529","DOI":"10.1038\/s41388-020-01450-5","article-title":"High-metastatic cancer cells derived exosomal miR92a-3p promotes epithelial-mesenchymal transition and metastasis of low-metastatic cancer cells by regulating PTEN\/Akt pathway in hepatocellular carcinoma","volume":"39","author":"Yang","year":"2020","journal-title":"Oncogene"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Kim, H., Lee, S., Shin, E., Seong, K.M., Jin, Y.W., Youn, H.S., and Youn, B.H. (2020). The Emerging Roles of Exosomes as EMT Regulators in Cancer. Cells, 9.","DOI":"10.3390\/cells9040861"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6201","DOI":"10.7314\/APJCP.2015.16.15.6201","article-title":"Roles of signaling pathways in the epithelial-mesenchymal transition in cancer","volume":"16","author":"Liu","year":"2015","journal-title":"Asia Pac. J. Cancer Prev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6843","DOI":"10.1002\/jcp.29578","article-title":"Exosome-mediated transfer of miR-1260b promotes cell invasion through Wnt\/\u03b2\u2013catenin signaling pathway in lung adenocarcinoma","volume":"235","author":"Xia","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12943-019-1019-x","article-title":"CAFs secreted exosomes promote metastasis and chemotherapy resistance by enhancing cell stemness and epithelial-mesenchymal transition in colorectal cancer","volume":"18","author":"Hu","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"19592","DOI":"10.18632\/oncotarget.14752","article-title":"Cancer-associated fibroblasts release exosomal microRNAs that dictate an aggressive phenotype in breast cancer","volume":"8","author":"Donnarumma","year":"2017","journal-title":"Oncotarget"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1093\/qjmed\/hcz093","article-title":"Snail1-dependent cancer-associated fibroblasts induce epithelial-mesenchymal transition in lung cancer cells via exosomes","volume":"112","author":"You","year":"2019","journal-title":"QJM Int. J. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.18632\/oncotarget.1336","article-title":"Induction and transport of Wnt 5a during macrophage-induced malignant invasion is mediated by two types of extracellular vesicles","volume":"4","author":"Menck","year":"2013","journal-title":"Oncotarget"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13287-019-1220-2","article-title":"Exosomes secreted by mesenchymal stromal\/stem cell-derived adipocytes promote breast cancer cell growth via activation of Hippo signaling pathway","volume":"10","author":"Wang","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"80666","DOI":"10.18632\/oncotarget.20881","article-title":"Exosomal miR-665 as a novel minimally invasive biomarker for hepatocellular carcinoma diagnosis and prognosis","volume":"8","author":"Qu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41419-018-0978-y","article-title":"miR-665 promotes hepatocellular carcinoma cell migration, invasion, and proliferation by decreasing Hippo signaling through targeting PTPRB","volume":"9","author":"Hu","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1111\/jcmm.12873","article-title":"Chronic myelogenous leukaemia exosomes modulate bone marrow microenvironment through activation of epidermal growth factor receptor","volume":"20","author":"Corrado","year":"2016","journal-title":"J. Cell. Mol. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2922","DOI":"10.4161\/cc.21386","article-title":"TAZ induces growth factor-independent proliferation through activation of EGFR ligand amphiregulin","volume":"11","author":"Yang","year":"2012","journal-title":"Cell Cycle"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/j.dld.2009.04.006","article-title":"Gastric cancer exosomes promote tumour cell proliferation through PI3K\/Akt and MAPK\/ERK activation","volume":"41","author":"Qu","year":"2009","journal-title":"Dig. Liver Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/nrc.2017.6","article-title":"Pre-metastatic niches: Organ-specific homes for metastases","volume":"17","author":"Peinado","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/S0140-6736(00)49915-0","article-title":"The distribution of secondary growths in cancer of the breast","volume":"133","author":"Paget","year":"1889","journal-title":"Lancet"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Ewing, J. (1928). Neoplastic Diseases: A Treatise on Tumours, W. B. Saunders Company.","DOI":"10.1097\/00000441-192808000-00014"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1093\/jnci\/57.5.1199","article-title":"Organ Selectivity for Implantation Survival and Growth of B16 Melanoma Variant Tumor Lines","volume":"57","author":"Fidler","year":"1976","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_56","first-page":"2281","article-title":"Role of organ selectivity in the determination of metastatic patterns of B16 melanoma","volume":"40","author":"Hart","year":"1980","journal-title":"Cancer Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1038\/nature04186","article-title":"VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche","volume":"438","author":"Kaplan","year":"2005","journal-title":"Nature"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.semcancer.2011.01.002","article-title":"The secreted factors responsible for pre-metastatic niche formation: Old sayings and new thoughts","volume":"21","author":"Peinado","year":"2011","journal-title":"Semin. Cancer Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.ceb.2014.06.012","article-title":"Complex metastatic niches: Already a target for therapy?","volume":"31","author":"Huelsken","year":"2014","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s43556-020-00022-z","article-title":"Characteristics of pre-metastatic niche: The landscape of molecular and cellular pathways","volume":"2","author":"Wang","year":"2021","journal-title":"Mol. Biomed."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"111810","DOI":"10.1016\/j.colsurfb.2021.111810","article-title":"Breast adenocarcinoma-derived exosomes lower first-contact de-adhesion strength of adenocarcinoma cells to brain endothelial layer","volume":"204","author":"Fazakas","year":"2021","journal-title":"Coll. Surf. B Biointerfaces"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Tominaga, N., Kosaka, N., Ono, M., Katsuda, T., Yoshioka, Y., Tamura, K., L\u00f6tvall, J., Nakagama, H., and Ochiya, T. (2015). Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood-brain barrier. Nat. Commun., 6.","DOI":"10.1038\/ncomms7716"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/nrclinonc.2011.58","article-title":"The biology of brain metastases\u2014Translation to new therapies","volume":"8","author":"Eichler","year":"2011","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Lu, Y., Chen, L., Li, L., and Cao, Y. (2020). Exosomes derived from brain metastatic breast cancer cells destroy the blood-brain barrier by carrying lncRNA GS1-600G8.5. Biomed Res. Int., 2020.","DOI":"10.1155\/2020\/7461727"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.ccr.2014.03.007","article-title":"Cancer-Secreted miR-105 destroys vascular endothelial barriers to promote metastasis","volume":"25","author":"Zhou","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1096\/fj.201800428R","article-title":"Brain microvascular endothelial cell exosome-mediated S100A16 up-regulation confers small-cell lung cancer cell survival in brain","volume":"33","author":"Xu","year":"2019","journal-title":"FASEB J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1002\/JLB.3A0218-054R","article-title":"Leukemia-derived exosomes and cytokines pave the way for entry into the brain","volume":"105","author":"Kinjyo","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/ncb3094","article-title":"Breast-cancer-secreted miR-122 reprograms glucose metabolism in premetastatic niche to promote metastasis","volume":"17","author":"Fong","year":"2015","journal-title":"Nat. Cell Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1038\/s41556-019-0404-4","article-title":"Tumour exosomal CEMIP protein promotes cancer cell colonization in brain metastasis","volume":"21","author":"Rodrigues","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4316","DOI":"10.1158\/0008-5472.CAN-18-1102","article-title":"Loss of XIST in breast cancer activates MSN-c-Met and reprograms microglia via exosomal miRNA to promote brain metastasis","volume":"78","author":"Xing","year":"2018","journal-title":"Cancer Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1038\/nm.2753","article-title":"Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET","volume":"18","author":"Peinado","year":"2012","journal-title":"Nat. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/nature15376","article-title":"Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth","volume":"527","author":"Zhang","year":"2015","journal-title":"Nature"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/s41571-019-0181-9","article-title":"Vessel co-option in cancer","volume":"16","author":"Kuczynski","year":"2019","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12929-014-0097-8","article-title":"Up-regulation of S100A16 expression promotes epithelial-mesenchymal transition via Notch1 pathway in breast cancer","volume":"21","author":"Zhou","year":"2014","journal-title":"J. Biomed. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1703244","DOI":"10.1080\/20013078.2019.1703244","article-title":"Inhibiting extracellular vesicles formation and release: A review of EV inhibitors","volume":"9","author":"Catalano","year":"2020","journal-title":"J. Extracell. Vesicles"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nrd3978","article-title":"Extracellular vesicles: Biology and emerging therapeutic opportunities","volume":"12","author":"Breakefield","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Rashed, M.H., Bayraktar, E., Helal, G.K., Abd-Ellah, M.F., Amero, P., Chavez-Reyes, A., and Rodriguez-Aguayo, C. (2017). Exosomes: From garbage bins to promising therapeutic targets. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18030538"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.canlet.2017.08.020","article-title":"Manumycin A suppresses exosome biogenesis and secretion via targeted inhibition of Ras\/Raf\/ERK1\/2 signaling and hnRNP H1 in castration-resistant prostate cancer cells","volume":"408","author":"Datta","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"F963","DOI":"10.1152\/ajprenal.00078.2017","article-title":"Exosome production and its regulation of EGFR during wound healing in renal tubular cells","volume":"312","author":"Zhou","year":"2017","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.biomaterials.2016.10.006","article-title":"Convective exosome-tracing microfluidics for analysis of cell-non-autonomous neurogenesis","volume":"112","author":"Oh","year":"2017","journal-title":"Biomaterials"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1002\/cbf.3276","article-title":"Exosomal DNMT1 mediates cisplatin resistance in ovarian cancer","volume":"35","author":"Cao","year":"2017","journal-title":"Cell Biochem. Funct."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1111\/cas.13310","article-title":"Accelerated growth of B16BL6 tumor in mice through efficient uptake of their own exosomes by B16BL6 cells","volume":"108","author":"Matsumoto","year":"2017","journal-title":"Cancer Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.jbior.2014.10.002","article-title":"Roles and regulation of neutral sphingomyelinase-2 in cellular and pathological processes","volume":"57","author":"Shamseddine","year":"2015","journal-title":"Adv. Biol. Regul."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1038\/onc.2016.353","article-title":"Cancer-associated fibroblast exosomes regulate survival and proliferation of pancreatic cancer cells","volume":"36","author":"Richards","year":"2017","journal-title":"Oncogene"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Hu, Y., Yan, C., Mu, L., Huang, K., Li, X., Tao, D., Wu, Y., and Qin, J. (2015). Fibroblast-derived exosomes contribute to chemoresistance through priming cancer stem cells in colorectal cancer. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0125625"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"24585","DOI":"10.18632\/oncotarget.8358","article-title":"Exosomes derived from gefitinib-treated EGFR-mutant lung cancer cells alter cisplatin sensitivity via up-regulating autophagy","volume":"7","author":"Li","year":"2016","journal-title":"Oncotarget"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1378056","DOI":"10.1080\/20013078.2017.1378056","article-title":"Neutral sphingomyelinases control extracellular vesicles budding from the plasma membrane","volume":"6","author":"Menck","year":"2017","journal-title":"J. Extracell. Vesicles"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4920","DOI":"10.1158\/0008-5472.CAN-12-0925","article-title":"Rab27a supports exosome-dependent and -independent mechanisms that modify the tumor microenvironment and can promote tumor progression","volume":"72","author":"Bobrie","year":"2012","journal-title":"Cancer Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5772\/61186","article-title":"Exosomes: Mechanisms of uptake","volume":"4","author":"McKelvey","year":"2015","journal-title":"J. Circ. Biomark."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.canlet.2009.03.041","article-title":"Tumor-derived microvesicles modulate the establishment of metastatic melanoma in a phosphatidylserine-dependent manner","volume":"283","author":"Lima","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3794","DOI":"10.1073\/pnas.0804543106","article-title":"Endothelial expression of autocrine VEGF upon the uptake of tumor-derived microvesicles containing oncogenic EGFR","volume":"106","author":"Meehan","year":"2009","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"17380","DOI":"10.1073\/pnas.1304266110","article-title":"Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity","volume":"110","author":"Christianson","year":"2013","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/s11060-013-1235-y","article-title":"Heparin blocks transfer of extracellular vesicles between donor and recipient cells","volume":"115","author":"Atai","year":"2013","journal-title":"J. Neurooncol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"3352","DOI":"10.1073\/pnas.061615598","article-title":"Heparin and cancer revisited: Mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis","volume":"98","author":"Borsig","year":"2001","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.critrevonc.2006.07.007","article-title":"Mechanisms of heparin induced anti-cancer activity in experimental cancer models","volume":"61","author":"Niers","year":"2007","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1186\/1479-5876-10-134","article-title":"Exosome removal as a therapeutic adjuvant in cancer","volume":"10","author":"Marleau","year":"2012","journal-title":"J. Transl. Med."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Antimisiaris, S.G., Mourtas, S., and Marazioti, A. (2018). Exosomes and exosome-inspired vesicles for targeted drug delivery. Pharmaceutics, 10.","DOI":"10.20944\/preprints201810.0507.v1"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"789","DOI":"10.7150\/thno.18133","article-title":"Progress in exosome isolation techniques","volume":"7","author":"Li","year":"2017","journal-title":"Theranostics"},{"key":"ref_99","first-page":"1","article-title":"Isolation and Characterization of Exosomes from Cell Culture Supernatants and Biological Fluids","volume":"30","author":"Amigorena","year":"2006","journal-title":"Curr. Protoc. Cell Biol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40486-017-0049-7","article-title":"Methods to isolate extracellular vesicles for diagnosis","volume":"5","author":"Kang","year":"2017","journal-title":"Micro Nano Syst. Lett."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1101\/pdb.top074476","article-title":"Strategies for isolation of exosomes","volume":"2015","author":"Zeringer","year":"2015","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.ymeth.2012.01.002","article-title":"Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes","volume":"56","author":"Tauro","year":"2012","journal-title":"Methods"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0022-1759(02)00330-7","article-title":"Production and characterization of clinical grade exosomes derived from dendritic cells","volume":"270","author":"Lamparski","year":"2002","journal-title":"J. Immunol. Methods"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1038\/mt.2010.105","article-title":"A novel nanoparticle drug delivery system: The anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes","volume":"18","author":"Sun","year":"2010","journal-title":"Mol. Ther."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1038\/mt.2011.164","article-title":"Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain","volume":"19","author":"Zhuang","year":"2011","journal-title":"Mol. Ther."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/nbt.1807","article-title":"Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes","volume":"29","author":"Seow","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Wahlgren, J., Karlson, T.D.L., Brisslert, M., Vaziri Sani, F., Telemo, E., Sunnerhagen, P., and Valadi, H. (2012). Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes. Nucleic Acids Res., 40.","DOI":"10.1093\/nar\/gks463"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.jconrel.2013.08.014","article-title":"Electroporation-induced siRNA precipitation obscures the efficiency of siRNA loading into extracellular vesicles","volume":"172","author":"Kooijmans","year":"2013","journal-title":"J. Control. Release"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1007\/s10616-016-9952-7","article-title":"Evaluation of electroporation-induced adverse effects on adipose-derived stem cell exosomes","volume":"68","author":"Johnsen","year":"2016","journal-title":"Cytotechnology"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.nano.2015.10.012","article-title":"Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells","volume":"12","author":"Kim","year":"2016","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.jconrel.2014.11.029","article-title":"Active loading into extracellular vesicles significantly improves the cellular uptake and photodynamic effect of porphyrins","volume":"205","author":"Fuhrmann","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"21933","DOI":"10.1038\/srep21933","article-title":"Engineering hybrid exosomes by membrane fusion with liposomes","volume":"6","author":"Sato","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s11101-010-9183-z","article-title":"Saponins as cytotoxic agents: A review","volume":"9","author":"Podolak","year":"2010","journal-title":"Phytochem. Rev."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/aps.2017.12","article-title":"Engineering exosomes as refined biological nanoplatforms for drug delivery","volume":"38","author":"Luan","year":"2017","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"13853","DOI":"10.1021\/acsnano.9b04397","article-title":"Tumor-derived extracellular vesicles breach the intact blood-brain barrier via transcytosis","volume":"13","author":"Morad","year":"2019","journal-title":"ACS Nano"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1007\/s12195-016-0458-3","article-title":"Elucidation of Exosome Migration Across the Blood\u2013Brain Barrier Model In Vitro","volume":"9","author":"Chen","year":"2016","journal-title":"Cell. Mol. Bioeng."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1007\/s11095-014-1593-y","article-title":"Exosome delivered anticancer drugs across the blood-brain barrier for brain cancer therapy in Danio rerio","volume":"32","author":"Yang","year":"2015","journal-title":"Pharm. Res."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Melzer, C., Rehn, V., Yang, Y., B\u00e4hre, H., von der Ohe, J., and Hass, R. (2019). Taxol-loaded MSC-Derived exosomes provide a therapeutic vehicle to target metastatic breast cancer and other carcinoma cells. Cancers, 11.","DOI":"10.3390\/cancers11060798"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.surg.2007.03.011","article-title":"Effectiveness of siRNA uptake in target tissues by various delivery methods","volume":"142","author":"Larson","year":"2007","journal-title":"Surgery"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/cgt.2016.78","article-title":"Extracellular vesicle-mediated suicide mRNA\/protein delivery inhibits glioblastoma tumor growth in vivo","volume":"24","author":"Erkan","year":"2017","journal-title":"Cancer Gene Ther."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"e126","DOI":"10.1038\/mtna.2013.60","article-title":"Delivery of Functional Anti-miR-9 by Mesenchymal stem cell\u2013derived exosomes to glioblastoma multiforme cells conferred chemosensitivity","volume":"2","author":"Munoz","year":"2013","journal-title":"Mol. Ther. Nucl. Acids"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1208\/s12248-016-0015-y","article-title":"Delivery of Small Interfering RNA to Inhibit vascular endothelial growth factor in zebrafish using natural brain endothelia cell-secreted exosome nanovesicles for the treatment of brain cancer","volume":"19","author":"Yang","year":"2017","journal-title":"AAPS J."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.canlet.2013.02.019","article-title":"Exosomes from marrow stromal cells expressing miR-146b inhibit glioma growth","volume":"335","author":"Katakowski","year":"2013","journal-title":"Cancer Lett."},{"key":"ref_124","first-page":"1","article-title":"The antitumor effect of gene-engineered exosomes in the treatment of brain metastasis of breast cancer","volume":"10","author":"Liu","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/31116","article-title":"Chemokines beyond inflammation","volume":"393","author":"Horuk","year":"1998","journal-title":"Nature"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"3213","DOI":"10.1161\/01.CIR.0000147609.39780.02","article-title":"Mobilization of CD34\/CXCR4 +, CD34\/CD117 +, c-met + stem cells, and mononuclear cells expressing early cardiac, muscle, and endothelial markers into peripheral blood in patients with acute myocardial infarction","volume":"110","author":"Wojakowski","year":"2004","journal-title":"Circulation"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2808","DOI":"10.1172\/JCI28310","article-title":"Hematopoietic stem cells proliferate until after birth and show a reversible phase-specific engraftment defect","volume":"116","author":"Bowie","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/5517","article-title":"Tumoricidal activity of tumor necrosis factor\u2013related apoptosis\u2013Inducing ligand in vivo","volume":"5","author":"Walczak","year":"1999","journal-title":"Nat. Med."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"171","DOI":"10.12998\/wjcc.v7.i2.171","article-title":"Clinical significance of exosomes as potential biomarkers in cancer","volume":"7","author":"Wong","year":"2019","journal-title":"World J. Clin. Cases"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1038\/ncb1800","article-title":"Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers","volume":"10","author":"Skog","year":"2008","journal-title":"Nat. Cell Biol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1093\/neuonc\/not218","article-title":"A small noncoding RNA signature found in exosomes of GBM patient serum as a diagnostic tool","volume":"16","author":"Manterola","year":"2014","journal-title":"Neuro-oncology"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s11060-015-2051-3","article-title":"Initial evidence that blood-borne microvesicles are biomarkers for recurrence and survival in newly diagnosed glioblastoma patients","volume":"127","author":"Evans","year":"2016","journal-title":"J. Neurooncol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1093\/neuonc\/noy187","article-title":"Characterization of single microvesicles in plasma from glioblastoma patients","volume":"21","author":"Fraser","year":"2019","journal-title":"Neuro-oncology"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1021\/acsnano.7b07060","article-title":"Multiplexed profiling of single extracellular vesicles","volume":"12","author":"Lee","year":"2018","journal-title":"ACS Nano"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1038\/nm.2994","article-title":"Protein typing of circulating microvesicles allows real-time monitoring of glioblastoma therapy","volume":"18","author":"Shao","year":"2012","journal-title":"Nat. Med."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Tucci, M., Passarelli, A., Mannavola, F., Stefania, L., Antonio, P., Capone, M., Madonna, G., Lopalco, P., and Silvestris, F. (2018). Serum exosomes as predictors of clinical response to ipilimumab in metastatic melanoma. Oncoimmunology, 7.","DOI":"10.1080\/2162402X.2017.1387706"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.cca.2015.12.031","article-title":"Circulating melanoma exosomes as diagnostic and prognosis biomarkers","volume":"454","author":"Alegre","year":"2016","journal-title":"Clin. Chim. Acta"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1002\/elps.201000598","article-title":"Proteomic identification of exosomal LRG1: A potential urinary biomarker for detecting NSCLC","volume":"32","author":"Li","year":"2011","journal-title":"Electrophoresis"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1021\/acs.jproteome.7b00770","article-title":"Comparative proteomic analysis of exosomes and microvesicles in human saliva for lung cancer","volume":"17","author":"Sun","year":"2018","journal-title":"J. Proteome Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7150\/ijbs.27796","article-title":"Current progresses of exosomes as cancer diagnostic and prognostic biomarkers","volume":"15","author":"Huang","year":"2019","journal-title":"Int. J. Biol. Sci."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s11060-011-0537-1","article-title":"Exosome-loaded dendritic cells elicit tumor-specific CD8+ cytotoxic T cells in patients with glioma","volume":"104","author":"Bu","year":"2011","journal-title":"J. Neurooncol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1779991","DOI":"10.1080\/2162402X.2020.1779991","article-title":"Tumor-derived exosomes: The next generation of promising cell-free vaccines in cancer immunotherapy","volume":"9","author":"Naseri","year":"2020","journal-title":"Oncoimmunology"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1038\/s41596-019-0126-x","article-title":"Asymmetric-flow field-flow fractionation technology for exomere and small extracellular vesicle separation and characterization","volume":"14","author":"Zhang","year":"2019","journal-title":"Nat. Protoc."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"De Almeida Fuzeta, M., Bernardes, N., Oliveira, F.D., Costa, A.C., Fernandes-Platzgummer, A., Farinha, J.P., Rodrigues, C.A.V., Jung, S., Tseng, R.-J., and Milligan, W. (2020). Scalable production of human mesenchymal stromal cell-derived extracellular vesicles under serum-\/xeno-free conditions in a microcarrier-based bioreactor culture system. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.553444"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/19\/10899\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:10:44Z","timestamp":1760166644000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/19\/10899"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,8]]},"references-count":144,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["ijms221910899"],"URL":"https:\/\/doi.org\/10.3390\/ijms221910899","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,8]]}}}