{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:19:45Z","timestamp":1786976385493,"version":"build-2736575974"},"reference-count":59,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T00:00:00Z","timestamp":1711670400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LZ23H040001"],"award-info":[{"award-number":["LZ23H040001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Microglia\u2010mediated inflammation is involved in the pathogenesis of Alzheimer's disease (AD), whereas human fibroblast growth factor 21 (hFGF21)\u00a0has demonstrated the ability to regulate microglia activation in Parkinson's disease, indicating a potential therapeutic role in AD. However, challenges such as aggregation, rapid inactivation, and the blood\u2013brain barrier hinder its effectiveness in treating AD. This study develops targeted delivery of hFGF21 to activated microglia using BV2 cell membrane\u2010coated PEGylated liposomes (hFGF21@BCM\u2010LIP), preserving the bioactivity of hFGF21. In vitro, hFGF21@BCM\u2010LIP specifically targets A\u03b2\n                    <jats:sub>1\u201042<\/jats:sub>\n                    \u2010induced BV2 cells, with uptake hindered by anti\u2010VCAM\u20101 antibody, indicating the importance of VCAM\u20101 and integrin \u03b14\/\u03b21 interaction in targeted delivery to BV2 cells. In vivo, following subcutaneous injection near the lymph nodes of the neck, hFGF21@BCM\u2010LIP diffuses into lymph nodes and distributes along the meningeal lymphatic vasculature and brain parenchyma in amyloid\u2010beta (A\u03b2\n                    <jats:sub>1\u201042<\/jats:sub>\n                    )\u2010induced mice. Furthermore, the administration of hFGF21@BCM\u2010LIP to activated microglia improves cognitive deficits caused by A\u03b2\n                    <jats:sub>1\u201042<\/jats:sub>\n                    and reduces levels of tau, p\u2010Tau, and BACE1. It also decreases interleukin\u20106 \u00a0(IL\u20106) and tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) release while increasing interleukin\u201010 (IL\u201010)\u00a0release both in vivo and in vitro. These results indicate that hFGF21@BCM\u2010LIP can be a promising treatment for AD, by effectively crossing the blood\u2013brain barrier and targeting delivery to brain microglia via the neck\u2010meningeal lymphatic vasculature\u2010brain parenchyma pathways.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202400125","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T15:43:44Z","timestamp":1711035824000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["BV2 Membrane\u2010Coated PEGylated\u2010Liposomes Delivered hFGF21 to Cortical and Hippocampal Microglia for Alzheimer's Disease Therapy"],"prefix":"10.1002","volume":"13","author":[{"given":"Heng\u2010Cai","family":"Wang","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou Zhejiang Province 325035 China"},{"name":"Research Institute of Pharmaceutical Sciences College of Pharmacy Chonnam National University  Gwangju 61186 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou Zhejiang Province 325035 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou Zhejiang Province 325035 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong\u2010Hui","family":"Han","sequence":"additional","affiliation":[{"name":"Oujiang Laboratory Zhejiang Lab for Regenerative Medicine Vision and Brain Health  Wenzhou Zhejiang Province 325101 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou Zhejiang Province 325035 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui\u2010Tao","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou Zhejiang Province 325035 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwonseop","family":"Kim","sequence":"additional","affiliation":[{"name":"Research Institute of Pharmaceutical Sciences College of Pharmacy Chonnam National University  Gwangju 61186 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6819-3231","authenticated-orcid":false,"given":"Ying\u2010Zheng","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou Zhejiang Province 325035 China"},{"name":"Cixi Biomedical Research Institute Wenzhou Medical University  Ningbo Zhejiang Province 315302 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi\u2010Chong","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou Zhejiang Province 325035 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,29]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1088-4"},{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4338"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-020-00435-y"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2018101064"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-021-00354-2"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021115-105339"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-015-9789-3"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.01.004"},{"key":"e_1_2_9_5_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101133"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-15-0289"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00154"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-019-00151-6"},{"key":"e_1_2_9_7_3","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.778527"},{"key":"e_1_2_9_7_4","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-018-0729-3"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612825666190716101411"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2021.06.015"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2021.120763"},{"key":"e_1_2_9_9_3","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-020-02023-9"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.2174\/156720108785915078"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.9b00855"},{"key":"e_1_2_9_10_3","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S365974"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2018.01.018"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/nl500618u"},{"key":"e_1_2_9_11_3","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.9b03817"},{"key":"e_1_2_9_11_4","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.1c16543"},{"key":"e_1_2_9_11_5","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.0c09390"},{"key":"e_1_2_9_11_6","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.6b03148"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202001014"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2021.06.015"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-021-01776-4"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2018.05.011"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1039\/C6NR07581A"},{"key":"e_1_2_9_16_1","first-page":"163","volume":"118","author":"Sun B. L.","year":"2018","journal-title":"Prog. Neurobiol."},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1419-5"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1912-x"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20142290"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.0c01806"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2017.05.001"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.1080\/10717544.2019.1587044"},{"key":"e_1_2_9_21_3","doi-asserted-by":"publisher","DOI":"10.1080\/1061186X.2021.2023159"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2017.03.026"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0TB01063D"},{"key":"e_1_2_9_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-021-01085-y"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23606"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21675"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2011.164"},{"key":"e_1_2_9_26_2","doi-asserted-by":"publisher","DOI":"10.1039\/c3tb21238f"},{"key":"e_1_2_9_26_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2022.121971"},{"key":"e_1_2_9_26_4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2020.09.012"},{"key":"e_1_2_9_26_5","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.9b03753"},{"key":"e_1_2_9_26_6","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202003679"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2018.04.053"},{"key":"e_1_2_9_27_2","doi-asserted-by":"publisher","DOI":"10.1080\/1061186X.2018.1561886"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.8b00478"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14432"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2015.03.020"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)70016-5"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26158"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2019.02.034"}],"container-title":["Advanced Healthcare Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202400125","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T16:28:20Z","timestamp":1759768100000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adhm.202400125"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,29]]},"references-count":59,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1002\/adhm.202400125"],"URL":"https:\/\/doi.org\/10.1002\/adhm.202400125","archive":["Portico"],"relation":{},"ISSN":["2192-2640","2192-2659"],"issn-type":[{"value":"2192-2640","type":"print"},{"value":"2192-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,29]]},"assertion":[{"value":"2024-01-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2400125"}}