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While DPZ has multi\u2010faceted benefits, its clinical efficacy is constrained by poor BBB penetration, requiring high doses that lead to significant side effects. To overcome this, we developed a brain\u2010targeted nanotherapeutic utilizing apoferritin (AFn) nanoparticles loaded with DPZ (AFn\u2010DPZ). We demonstrate that this platform, by binding to the EphB1 receptor on the blood\u2013brain barrier, enables transient and reversible opening of the blood\u2013brain barrier, thereby facilitating efficient and targeted drug delivery. Following intravenous administration in an AD mouse model, AFn\u2010DPZ exhibited enhanced brain accumulation and sustained release of DPZ. This targeted delivery inhibited acetylcholinesterase activity, reduced amyloid plaque burden, alleviated neuroinflammation, attenuated oxidative damage, restored mitochondrial function, and upregulated the expression of brain\u2010derived neurotrophic factor (BDNF). Consequently, AFn\u2010DPZ treatment significantly improved cognitive performance compared to free DPZ. Our findings establish EphB1\u2010mediated facilitation of BBB traversal as a promising strategy for enhancing nanotherapeutic delivery to the brain, offering a potent approach to address the complex pathology of AD.<\/jats:p>","DOI":"10.1002\/advs.76480","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T16:06:29Z","timestamp":1783353989000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["EphB1\u2010Mediated Transient Blood\u2010Brain Barrier Opening Facilitates a Ferritin\u2010Based Nanotherapeutic for Alzheimer's Disease"],"prefix":"10.1002","volume":"13","author":[{"given":"Shilin","family":"Wen","sequence":"first","affiliation":[{"name":"Department of Rehabilitation The Third Affiliated Hospital of Zhejiang Chinese Medical University  Hangzhou Zhejiang China"},{"name":"Shulan International Medical College Zhejiang Shuren University  Hangzhou China"},{"name":"The Third 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