{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:49:57Z","timestamp":1791596997753,"version":"4.3.4"},"reference-count":48,"publisher":"Elsevier BV","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["iScience"],"published-print":{"date-parts":[[2026,9]]},"DOI":"10.1016\/j.isci.2026.117286","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T04:34:17Z","timestamp":1787373257000},"page":"117286","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Optimizing plasma-derived small extracellular vesicle purification to enhance downstream applications"],"prefix":"10.1016","volume":"29","author":[{"given":"Fanxiu","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiumei","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengsi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaodi","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuying","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Quan","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5838-193X","authenticated-orcid":false,"given":"Qi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.isci.2026.117286_bib1","doi-asserted-by":"crossref","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"Th\u00e9ry","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"10.1016\/j.isci.2026.117286_bib2","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1146\/annurev-cellbio-101512-122326","article-title":"Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles","volume":"30","author":"Colombo","year":"2014","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"10.1016\/j.isci.2026.117286_bib3","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":"10.1016\/j.isci.2026.117286_bib4","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.tcb.2015.01.004","article-title":"Ectosomes and exosomes: shedding the confusion between extracellular vesicles","volume":"25","author":"Cocucci","year":"2015","journal-title":"Trends Cell Biol."},{"key":"10.1016\/j.isci.2026.117286_bib5","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.blre.2012.12.002","article-title":"Extracellular vesicles in physiological and pathological conditions","volume":"27","author":"Yuana","year":"2013","journal-title":"Blood Rev."},{"key":"10.1016\/j.isci.2026.117286_bib6","doi-asserted-by":"crossref","DOI":"10.3390\/cancers15041307","article-title":"Extracellular Vesicles in Liquid Biopsies as Biomarkers for Solid Tumors","volume":"15","author":"Irmer","year":"2023","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.isci.2026.117286_bib7","doi-asserted-by":"crossref","DOI":"10.1016\/j.vesic.2022.100017","article-title":"Extracellular vesicles as novel therapeutic targets and diagnosis markers","volume":"1","author":"Zhang","year":"2022","journal-title":"Extracell. Vesicle"},{"key":"10.1016\/j.isci.2026.117286_bib8","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s11011-022-01114-1","article-title":"Blood-based biomarkers in Alzheimer's disease: a mini-review","volume":"38","author":"Padala","year":"2023","journal-title":"Metab. Brain Dis."},{"key":"10.1016\/j.isci.2026.117286_bib9","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s12987-022-00359-3","article-title":"Extracellular vesicles through the blood-brain barrier: a review","volume":"19","author":"Ramos-Zald\u00edvar","year":"2022","journal-title":"Fluids Barriers CNS"},{"key":"10.1016\/j.isci.2026.117286_bib10","doi-asserted-by":"crossref","first-page":"469","DOI":"10.2174\/1567205013666151116141603","article-title":"Diagnosis of Neurodegenerative Diseases: The Clinical Approach","volume":"13","author":"G\u00f3mez-R\u00edo","year":"2016","journal-title":"Curr. Alzheimer Res."},{"key":"10.1016\/j.isci.2026.117286_bib11","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":"10.1016\/j.isci.2026.117286_bib12","doi-asserted-by":"crossref","DOI":"10.1002\/jev2.12404","article-title":"Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches","volume":"13","author":"Welsh","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"10.1016\/j.isci.2026.117286_bib13","doi-asserted-by":"crossref","DOI":"10.3402\/jev.v4.29509","article-title":"High-speed centrifugation induces aggregation of extracellular vesicles","volume":"4","author":"Linares","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"10.1016\/j.isci.2026.117286_bib14","doi-asserted-by":"crossref","DOI":"10.1002\/smll.201702153","article-title":"Biological Functions and Current Advances in Isolation and Detection Strategies for Exosome Nanovesicles","volume":"14","author":"Boriachek","year":"2018","journal-title":"Small"},{"key":"10.1016\/j.isci.2026.117286_bib15","doi-asserted-by":"crossref","DOI":"10.3402\/jev.v4.27269","article-title":"Ready-made chromatography columns for extracellular vesicle isolation from plasma","volume":"4","author":"Welton","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"10.1016\/j.isci.2026.117286_bib16","doi-asserted-by":"crossref","first-page":"3354","DOI":"10.1002\/pmic.201300282","article-title":"Comparative proteomics evaluation of plasma exosome isolation techniques and assessment of the stability of exosomes in normal human blood plasma","volume":"13","author":"Kalra","year":"2013","journal-title":"Proteomics"},{"key":"10.1016\/j.isci.2026.117286_bib17","doi-asserted-by":"crossref","DOI":"10.1002\/jev2.12140","article-title":"Formation of a protein corona on the surface of extracellular vesicles in blood plasma","volume":"10","author":"T\u00f3th","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"10.1016\/j.isci.2026.117286_bib18","doi-asserted-by":"crossref","DOI":"10.3402\/jev.v3.23262","article-title":"Co-isolation of extracellular vesicles and high-density lipoproteins using density gradient ultracentrifugation","volume":"3","author":"Yuana","year":"2014","journal-title":"J. Extracell. Vesicles"},{"key":"10.1016\/j.isci.2026.117286_bib19","series-title":"StatPearls [Internet]","article-title":"Physiology, Cholesterol","author":"Huff","year":"2023"},{"key":"10.1016\/j.isci.2026.117286_bib20","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":"10.1016\/j.isci.2026.117286_bib21","doi-asserted-by":"crossref","first-page":"2873","DOI":"10.1007\/s00018-018-2773-4","article-title":"Detailed analysis of the plasma extracellular vesicle proteome after separation from lipoproteins","volume":"75","author":"Karimi","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.isci.2026.117286_bib22","doi-asserted-by":"crossref","first-page":"3177","DOI":"10.1007\/s00216-023-04684-w","article-title":"Depletion of abundant plasma proteins for extracellular vesicle proteome characterization: benefits and pitfalls","volume":"415","author":"Reymond","year":"2023","journal-title":"Anal. Bioanal. Chem."},{"key":"10.1016\/j.isci.2026.117286_bib23","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1161\/ATVBAHA.112.300741","article-title":"Characterization of levels and cellular transfer of circulating lipoprotein-bound microRNAs","volume":"33","author":"Wagner","year":"2013","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"10.1016\/j.isci.2026.117286_bib24","doi-asserted-by":"crossref","first-page":"402","DOI":"10.3389\/fendo.2018.00402","article-title":"Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation","volume":"9","author":"O'Brien","year":"2018","journal-title":"Front. Endocrinol."},{"key":"10.1016\/j.isci.2026.117286_bib25","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s13024-023-00613-8","article-title":"Cerebrospinal fluid lipoproteins inhibit alpha-synuclein aggregation by interacting with oligomeric species in seed amplification assays","volume":"18","author":"Bellomo","year":"2023","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.isci.2026.117286_bib26","doi-asserted-by":"crossref","DOI":"10.1080\/20013078.2018.1560809","article-title":"Comparison of small extracellular vesicles isolated from plasma by ultracentrifugation or size-exclusion chromatography: yield, purity and functional potential","volume":"8","author":"Takov","year":"2019","journal-title":"J. Extracell. Vesicles"},{"key":"10.1016\/j.isci.2026.117286_bib27","doi-asserted-by":"crossref","DOI":"10.1002\/jev2.12400","article-title":"A beginner's guide to study extracellular vesicles in human blood plasma and serum","volume":"13","author":"Nieuwland","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"10.1016\/j.isci.2026.117286_bib28","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.3389\/fphys.2018.01479","article-title":"Isolation of High-Purity Extracellular Vesicles by the Combination of Iodixanol Density Gradient Ultracentrifugation and Bind-Elute Chromatography From Blood Plasma","volume":"9","author":"On\u00f3di","year":"2018","journal-title":"Front. Physiol."},{"key":"10.1016\/j.isci.2026.117286_bib29","doi-asserted-by":"crossref","DOI":"10.1080\/20013078.2017.1308779","article-title":"Prospects and limitations of antibody-mediated clearing of lipoproteins from blood plasma prior to nanoparticle tracking analysis of extracellular vesicles","volume":"6","author":"M\u00f8rk","year":"2017","journal-title":"J. Extracell. Vesicles"},{"key":"10.1016\/j.isci.2026.117286_bib30","doi-asserted-by":"crossref","DOI":"10.1038\/srep23978","article-title":"ExtraPEG: A Polyethylene Glycol-Based Method for Enrichment of Extracellular Vesicles","volume":"6","author":"Rider","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.isci.2026.117286_bib31","doi-asserted-by":"crossref","DOI":"10.3402\/jev.v2i0.20360","article-title":"Standardization of sample collection, isolation and analysis methods in extracellular vesicle research","volume":"2","author":"Witwer","year":"2013","journal-title":"J. Extracell. Vesicles"},{"key":"10.1016\/j.isci.2026.117286_bib32","doi-asserted-by":"crossref","DOI":"10.1002\/jev2.12266","article-title":"Comparative analysis of tangential flow filtration and ultracentrifugation, both combined with subsequent size exclusion chromatography, for the isolation of small extracellular vesicles","volume":"11","author":"Visan","year":"2022","journal-title":"J. Extracell. Vesicles"},{"key":"10.1016\/j.isci.2026.117286_bib33","doi-asserted-by":"crossref","DOI":"10.1002\/jev2.12145","article-title":"Establishment of a simplified dichotomic size-exclusion chromatography for isolating extracellular vesicles toward clinical applications","volume":"10","author":"Guo","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"10.1016\/j.isci.2026.117286_bib34","doi-asserted-by":"crossref","DOI":"10.1080\/20013078.2019.1621131","article-title":"Different isolation approaches lead to diverse glycosylated extracellular vesicle populations","volume":"8","author":"Freitas","year":"2019","journal-title":"J. Extracell. Vesicles"},{"key":"10.1016\/j.isci.2026.117286_bib35","doi-asserted-by":"crossref","first-page":"13559","DOI":"10.1074\/jbc.M512306200","article-title":"The interaction between cytoplasmic prion protein and the hydrophobic lipid core of membrane correlates with neurotoxicity","volume":"281","author":"Wang","year":"2006","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.isci.2026.117286_bib36","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":"10.1016\/j.isci.2026.117286_bib37","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.cell.2020.07.009","article-title":"Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers","volume":"182","author":"Hoshino","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.isci.2026.117286_bib38","first-page":"3","article-title":"Isolation and characterization of exosomes from cell culture supernatants and biological fluids","volume":"30","author":"Thery","year":"2006","journal-title":"Curr Protoc Cell Biol Chapter"},{"key":"10.1016\/j.isci.2026.117286_bib39","doi-asserted-by":"crossref","DOI":"10.1242\/dmm.048929","article-title":"Implications of exosomes derived from cholesterol-accumulated astrocytes in Alzheimer's disease pathology","volume":"14","author":"Wu","year":"2021","journal-title":"Dis. Model. Mech."},{"key":"10.1016\/j.isci.2026.117286_bib40","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1161\/CIRCRESAHA.117.311767","article-title":"What Are We Looking At? Extracellular Vesicles, Lipoproteins, or Both?","volume":"121","author":"Simonsen","year":"2017","journal-title":"Circ. Res."},{"key":"10.1016\/j.isci.2026.117286_bib41","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1161\/CIRCULATIONAHA.122.063402","article-title":"Multiomics of Tissue Extracellular Vesicles Identifies Unique Modulators of Atherosclerosis and Calcific Aortic Valve Stenosis","volume":"148","author":"Blaser","year":"2023","journal-title":"Circulation"},{"key":"10.1016\/j.isci.2026.117286_bib42","doi-asserted-by":"crossref","first-page":"4739","DOI":"10.1021\/acs.analchem.1c00693","article-title":"Advances in Analytical Technologies for Extracellular Vesicles","volume":"93","author":"Yan","year":"2021","journal-title":"Anal. Chem."},{"key":"10.1016\/j.isci.2026.117286_bib43","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1016\/j.ijbiomac.2022.08.148","article-title":"Native PLGA nanoparticles regulate APP metabolism and protect neurons against beta-amyloid toxicity: Potential significance in Alzheimer's disease pathology","volume":"219","author":"Wu","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"10.1016\/j.isci.2026.117286_bib44","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s12964-024-01485-1","article-title":"Immunophenotype profile by flow cytometry reveals different subtypes of extracellular vesicles in porcine seminal plasma","volume":"22","author":"Barranco","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"10.1016\/j.isci.2026.117286_bib45","doi-asserted-by":"crossref","DOI":"10.1038\/srep36502","article-title":"A rapid, automated surface protein profiling of single circulating exosomes in human blood","volume":"6","author":"Kibria","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.isci.2026.117286_bib46","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1008139","article-title":"Structural evidence for the critical role of the prion protein hydrophobic region in forming an infectious prion","volume":"15","author":"Abskharon","year":"2019","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.isci.2026.117286_bib47","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s40478-021-01175-w","article-title":"Streamlined alpha-synuclein RT-QuIC assay for various biospecimens in Parkinson's disease and dementia with Lewy bodies","volume":"9","author":"Bargar","year":"2021","journal-title":"Acta Neuropathol. Commun."},{"key":"10.1016\/j.isci.2026.117286_bib48","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/nmeth.1322","article-title":"Universal sample preparation method for proteome analysis","volume":"6","author":"Wi\u015bniewski","year":"2009","journal-title":"Nat. Methods"}],"container-title":["iScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589004226026647?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589004226026647?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:01:01Z","timestamp":1791594061000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2589004226026647"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":48,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["S2589004226026647"],"URL":"https:\/\/doi.org\/10.1016\/j.isci.2026.117286","relation":{},"ISSN":["2589-0042"],"issn-type":[{"value":"2589-0042","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Optimizing plasma-derived small extracellular vesicle purification to enhance downstream applications","name":"articletitle","label":"Article Title"},{"value":"iScience","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.isci.2026.117286","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"117286"}}