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Based on this, a multifunctional nanodrug delivery system, termed OAF, was developed by encapsulating oridonin (ORI) into apoferritin (ApoFn), enabling simultaneous targeting of both brain and the liver through transferrin receptor 1 (TfR1). OAF upregulated the expression of low\u2010density lipoprotein receptor\u2010related protein 1 (LRP1) in cerebral capillary endothelial cells and hepatic parenchymal cells to promote A\u03b2 clearance from the brain and subsequent hepatic degradation. In AD mice, OAF treatment markedly reduced A\u03b2 deposition, neuroinflammation, and cognitive impairment, while ameliorating inflammation, oxidative stress, and mitochondrial dysfunction in both brain and liver. Overall, OAF synergistically combined A\u03b2 clearance, anti\u2010inflammatory, and antioxidant mechanisms, offering a novel therapeutic strategy for AD.<\/jats:p>","DOI":"10.1002\/advs.202523458","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T10:50:18Z","timestamp":1775559018000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Brain and Liver Dual\u2010Targeting Oridonin Nanoparticles to Enhance A\u03b2 Clearance for Alzheimer's Disease Therapy"],"prefix":"10.1002","volume":"13","author":[{"given":"Wenshuai","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Air Force Medical University  Xi'an China"},{"name":"Department of Pharmacology School of Pharmacy Air Force Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenting","family":"Hui","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Air Force Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sai","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Air Force Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qifeng","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Air Force Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Air Force Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bangle","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Air Force Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daozhou","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Air Force Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmacy Air Force Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6092-4406","authenticated-orcid":false,"given":"Siyuan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Air Force Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201044737\u2010x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/procel\/pwae026"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-95-2790-8"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.17345"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102481"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/b978\u20100\u201012\u2010804766\u20108.00013\u20103"},{"key":"e_1_2_10_8_1","volume-title":"Medicinal Plants in Parkinson's Therapy","author":"Rai S. 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