{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:54:40Z","timestamp":1791410080868,"version":"4.3.3"},"reference-count":60,"publisher":"Wiley","issue":"34","license":[{"start":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T00:00:00Z","timestamp":1720483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC3601200"],"award-info":[{"award-number":["2022YFC3601200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272609"],"award-info":[{"award-number":["82272609"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172546"],"award-info":[{"award-number":["82172546"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["51933011"],"award-info":[{"award-number":["51933011"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Alzheimer's disease (AD) is the most common age\u2010related neurodegenerative disorder leading to cognitive decline. Excessive cytosolic calcium (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ) accumulation plays a critical role in the pathogenesis of AD since it activates the NOD\u2010like receptor family, pyrin domain containing 3 (NLRP3), switches the endoplasmic reticulum (ER) unfolded protein response (UPR) toward proapoptotic signaling and promotes A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    seeding. Herein, a liposomal nanodrug (felodipine@LND) is developed incorporating a calcium channel antagonist felodipine for Alzheimer's disease treatment through a low\u2010intensity pulse ultrasound (LIPUS) irradiation\u2010assisted blood brain barrier (BBB)\u2010crossing drug delivery. The multifunctional felodipine@LND is effectively delivered to diseased brain through applying a LIPUS irradiation to the skull, which resulted in a series of positive effects against AD. Markedly, the nanodrug treatment switched the ER UPR toward antioxidant signaling, prevented the surface translocation of ER calreticulin (CALR) in microglia, and inhibited the NLRP3 activation and A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    seeding. In addition, it promoted the degradation of damaged mitochondria via mitophagy, thereby inhibiting the neuronal apoptosis. Therefore, the anxiety\u2010like behavior and cognitive impairment of 5xFAD mice with AD is significantly ameliorated, which manifested the potential of LIPUS \u2013 assisted BBB\u2010crossing delivery of felodipine@LND to serve as a paradigm for AD therapy based on the well\u2010recognized clinically available felodipine.\n                  <\/jats:p>","DOI":"10.1002\/advs.202401731","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T15:29:56Z","timestamp":1720538996000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Blood Brain Barrier\u2010Crossing Delivery of Felodipine Nanodrug Ameliorates Anxiety\u2010Like Behavior and Cognitive Impairment in Alzheimer's Disease"],"prefix":"10.1002","volume":"11","author":[{"given":"Xiaofei","family":"He","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Medicine The Third Affiliated Hospital Sun Yat\u2010sen University  600 Tianhe Road Guangzhou Guangdong 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine Guangzhou First People's Hospital  Guangzhou 510180 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sicong","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Materials Science and Engineering Sun Yat\u2010sen University  Guangzhou 510275 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zecong","family":"Xiao","sequence":"additional","affiliation":[{"name":"Nanomedicine Research Center The Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Laboratory Animals Guangdong Laboratory Animals Monitoring Institute  11 Fengxin Road Guangzhou Guangdong 510663 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zejie","family":"Zuo","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine The Third Affiliated Hospital Sun Yat\u2010sen University  600 Tianhe Road Guangzhou Guangdong 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine The Third Affiliated Hospital Sun Yat\u2010sen University  600 Tianhe Road Guangzhou Guangdong 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4271-0310","authenticated-orcid":false,"given":"Xintao","family":"Shuai","sequence":"additional","affiliation":[{"name":"Nanomedicine Research Center The Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiqing","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine The Third Affiliated Hospital Sun Yat\u2010sen University  600 Tianhe Road Guangzhou Guangdong 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiquan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine The Third Affiliated Hospital Sun Yat\u2010sen University  600 Tianhe Road Guangzhou Guangdong 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,9]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32205-4"},{"key":"e_1_2_8_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abc7031"},{"key":"e_1_2_8_1_3","doi-asserted-by":"publisher","DOI":"10.1002\/bmm2.12011"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/EXP.20230029"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-45656-7"},{"key":"e_1_2_8_2_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2021.101503"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.06.005"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.056"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.09.001"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-00913-5"},{"key":"e_1_2_8_5_3","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23074"},{"key":"e_1_2_8_5_4","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.02.025"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-018-0195-3"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0167-y"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25143"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abe3600"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0617-19.2019"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.03.004"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2000-8179"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.2174\/1574886310666150514114619"},{"key":"e_1_2_8_12_3","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09494-2"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3109\/15563650.2014.965827"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199015004-00026"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2018.06.024"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.3390\/nano12132140"},{"key":"e_1_2_8_14_3","doi-asserted-by":"publisher","DOI":"10.1002\/bmm2.12018"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2022.05.042"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-019-03204-0"},{"key":"e_1_2_8_15_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.09.003"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaf6086"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2308719"},{"key":"e_1_2_8_18_1","first-page":"99","volume-title":"Methods in Molecular Biology","author":"Kraeuter A.","year":"2019"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.04.015"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39172-3"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2018.07.004"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3380"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2017.11.018"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2020.1840796"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1636"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.2174\/1567205016666191210091302"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao6047"},{"key":"e_1_2_8_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06373-1"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0679-22.2022"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0332-9"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2017.44"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X15608201"},{"key":"e_1_2_8_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adg6618"},{"key":"e_1_2_8_31_3","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.5978"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmm2.12010"},{"key":"e_1_2_8_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioadv.2022.213102"},{"key":"e_1_2_8_32_3","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.123.043005"},{"key":"e_1_2_8_32_4","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60327-360-2_13"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-022-00292-3"},{"key":"e_1_2_8_33_2","doi-asserted-by":"publisher","DOI":"10.2217\/nnm.13.204"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2018.05.019"},{"key":"e_1_2_8_35_1","first-page":"2831","volume":"24","author":"Shen Y.","year":"2014","journal-title":"Biomed. Mater. Eng."},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13657"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10339-011-0430-z"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.116"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232113606"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202401731","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T13:11:50Z","timestamp":1759756310000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202401731"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,9]]},"references-count":60,"journal-issue":{"issue":"34","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1002\/advs.202401731"],"URL":"https:\/\/doi.org\/10.1002\/advs.202401731","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,9]]},"assertion":[{"value":"2024-02-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2401731"}}