{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T10:18:12Z","timestamp":1784542692596,"version":"3.55.0"},"reference-count":75,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"14","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2024,4,5]]},"abstract":"<jats:p>Amyloid aggregation of \u03b1-synuclein (\u03b1SN) protein amplifies the pathogenesis of neurodegenerative diseases (NDs) such as Parkinson\u2019s disease (PD). Consequently, blocking aggregation or redirecting self-assembly to less toxic aggregates could be therapeutic. Here, we improve brain-specific nanocarriers using a hybrid of exosomes (Ex) from human umbilical cord mesenchymal stem cells (hUC MSCs) and nanoliposomes containing baicalein (Ex-NLP\u2013Ba) and oleuropein (Ex-NLP\u2013Ole). The hybrids contained both lipid membranes, Ex proteins, and baicalein or oleuropein. Fluorescence resonance energy transfer analysis confirmed their proper integration. The hybrids reduced the extent of \u03b1SN fibrillation and interfered with secondary nucleation and disaggregation. They not only reduced \u03b1SN pathogenicity but also enhanced drug internalization into cells, surpassing the efficacy of NLP alone, and also crossed the blood-brain barrier in a cellular model. We conclude that Ex can be successfully extracted and efficiently merged with NLPs while retaining its original properties, demonstrating great potential as a theranostic drug delivery vehicle against NDs like PD.<\/jats:p>","DOI":"10.1126\/sciadv.adl3406","type":"journal-article","created":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T17:58:27Z","timestamp":1712167107000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":31,"title":["The impact of hUC MSC\u2013derived exosome-nanoliposome hybrids on \u03b1-synuclein fibrillation and neurotoxicity"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0928-3743","authenticated-orcid":true,"given":"Farhang","family":"Aliakbari","sequence":"first","affiliation":[{"name":"Bioprocess Engineering Department, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran."},{"name":"Molecular Medicine Group, Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimia","family":"Marzookian","sequence":"additional","affiliation":[{"name":"Bioprocess Engineering Department, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soha","family":"Parsafar","sequence":"additional","affiliation":[{"name":"Bioprocess Engineering Department, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamdam","family":"Hourfar","sequence":"additional","affiliation":[{"name":"Bioprocess Engineering Department, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3453-3190","authenticated-orcid":true,"given":"Zahra","family":"Nayeri","sequence":"additional","affiliation":[{"name":"Bioprocess Engineering Department, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6248-4344","authenticated-orcid":true,"given":"Arghavan","family":"Fattahi","sequence":"additional","affiliation":[{"name":"Bioprocess Engineering Department, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Raeiji","sequence":"additional","affiliation":[{"name":"Bioprocess Engineering Department, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narges Nasrollahi","family":"Boroujeni","sequence":"additional","affiliation":[{"name":"Bioprocess Engineering Department, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran."},{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2918-8989","authenticated-orcid":true,"given":"Daniel E.","family":"Otzen","sequence":"additional","affiliation":[{"name":"Interdisciplinary Nanoscience Centre (iNANO) and Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 14, DK-8000 Aarhus C, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0751-8772","authenticated-orcid":true,"given":"Dina","family":"Morshedi","sequence":"additional","affiliation":[{"name":"Bioprocess Engineering Department, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-019-0172-x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1353-8020(13)70017-8"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32625-1"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1227157"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom10030391"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2018.08.005"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202007765"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2022.03.092"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2020.e04737"},{"key":"e_1_3_2_11_2","first-page":"431","article-title":"Identification and characterization of a compound from Cuminum cyminum essential oil with antifibrilation and cytotoxic effect","volume":"9","author":"Morshedi D.","year":"2014","unstructured":"D. Morshedi, T. S. Kesejini, F. Aliakbari, R. Karami-Osboo, M. Shakibaei, A. T. Marvian, M. Khalifeh, M. Soroosh, Identification and characterization of a compound from Cuminum cyminum essential oil with antifibrilation and cytotoxic effect. Res. Pharm. Sci. 9, 431\u2013443 (2014).","journal-title":"Res. Pharm. Sci."},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/1750-3841.13016"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.554667"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0184483"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2017.11.023"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2020.119895"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.005723"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1039\/C8NR00632F"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5411.143"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2018.1535750"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18091852"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2019.100249"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.3410\/B3-15"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13302"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-05034-x"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1586\/epr.09.17"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1596"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001604"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2013.00182"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2013.10.004"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22157763"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2575"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.118.008737"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2020.02.001"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2019.12.020"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-019-1548-7"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-020-1563-8"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.8b02053"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.201700611"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nano.2014.08.004"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0033583517000026"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2018.02.007"},{"key":"e_1_3_2_43_2","first-page":"8","article-title":"Genotoxicity of different nanocarriers: Possible modifications for the delivery of nucleic acids","volume":"10","author":"Shah V.","year":"2013","unstructured":"V. Shah, O. Taratula, O. B. Garbuzenko, M. L. Patil, R. Savla, M. Zhang, T. Minko, Genotoxicity of different nanocarriers: Possible modifications for the delivery of nucleic acids. Curr. Drug Discov. Technol. 10, 8\u201315 (2013).","journal-title":"Curr. Drug Discov. Technol."},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/469679"},{"key":"e_1_3_2_45_2","doi-asserted-by":"crossref","unstructured":"R. P. Araldi F. D\u2019amelio H. Vigerelli T. C. de Melo I. Kerkis Stem cell-derived exosomes as therapeutic approach for neurodegenerative disorders: From biology to biotechnology. 9 2663 (2020).","DOI":"10.3390\/cells9122663"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep21933"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-022-01264-5"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M403129200"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr500279h"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-26645-5"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2020.1728384"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008919200"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom11101419"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi900539p"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-022-02421-8"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113908"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1632"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2022.12.134"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-11220-1"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1602\/neurorx.2.1.3"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.00072"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2011.03.046"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2022.08.088"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00894-010-0942-y"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2010.11.002"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1177\/0748233711413799"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2023.2218495"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1080\/10717544.2019.1582730"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a020412"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-18-0891"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12195-016-0458-3"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-023-01828-z"},{"key":"e_1_3_2_73_2","doi-asserted-by":"crossref","unstructured":"K. Marzookian F. Aliakbari H. Hourfar D. E. Otzen D. Morshedi Secretome Derived from Umbilical cord mesenchymal stem cells exerts protective impacts on the blood-brain barrier against \u03b1-synuclein aggregates using an in vitro model. bioRxiv 2023.10.21.562544 (2023). https:\/\/doi.org\/10.1101\/2023.10.21.562544.","DOI":"10.1101\/2023.10.21.562544"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi701899y"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1039\/C5NR05663B"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adl3406","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T17:59:29Z","timestamp":1712167169000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adl3406"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,5]]},"references-count":75,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2024,4,5]]}},"alternative-id":["10.1126\/sciadv.adl3406"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adl3406","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,5]]},"assertion":[{"value":"2023-10-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadl3406"}}