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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,9,15]]},"abstract":"<jats:p>\n                    Antibody-based immunotherapy targeting amyloid-\u03b2 (A\u03b2) is a promising approach for Alzheimer\u2019s disease (AD). However, its efficacy is limited by rapid hepatic sequestration, complement activation, and liver dysfunction. In this study, we synthesized low-immunogenic 450-nm functionalized mesoporous silica nanoparticles (PEG-MSN-1F12) by conjugating the anti-A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    monoclonal antibody 1F12 to polyethylene glycol-modified mesoporous silica nanoparticles to address these challenges. In APP\/PS1 mice, intravenous PEG-MSN-1F12 administration markedly enhanced peripheral A\u03b2 clearance, promoted intestinal excretion, reshaped gut microbiota, and alleviated intestinal inflammation, thus reducing AD-associated hepatic burden. Peripheral A\u03b2 removal further led to decreased brain A\u03b2 deposition, attenuated microglial activation, and improved cognition. These findings highlight that the use of particle size\u2013engineered antibody\u2013nanoparticle conjugates is a safe and effective strategy to overcome hepatic sequestration, augment A\u03b2 clearance, and improve AD outcomes.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2603034123","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T17:47:37Z","timestamp":1788889657000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Size-tailored nanoparticle\u2013antibody conjugates overcome hepatic sequestration in Alzheimer\u2019s disease treatment"],"prefix":"10.1073","volume":"123","author":[{"given":"Xuewei","family":"Du","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ab0at74","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Digital Medical Engineering, Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical 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