{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T09:17:57Z","timestamp":1787822277298,"version":"build-2784847793"},"reference-count":56,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biomed Mater Res"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Cholinergic dysfunction, oxidative stress, neuroinflammation, and proteinopathies are among the major hallmarks of Alzheimer's disease (AD). This study aimed to develop and evaluate the therapeutic potential of multilayered silica\u2010based\/chitosan\u2010coated nanoparticles (Si@CsNPs) co\u2010loaded with quercetin (QUR) and tamoxifen (TAM) in an LPS\u2010induced neuroinflammatory murine model exhibiting AD\u2010like neuropathological alterations associated with bacterial endotoxin exposure. Molecular docking and target prediction analyses suggested that TAM may exert partial cholinesterase inhibitory activity and potentially interact with muscarinic receptor\u2010 and epidermal growth factor receptor (EGFR)\u2010associated pathways, which are implicated in neuroinflammation and oxidative stress regulation. The resulting silica\u2010based\/chitosan\u2010coated nanoparticles (Si@CsNPs) co\u2010loaded with QUR and TAM (QUR\/TAM\u2010Si@CsNPs) were spherical in shape, exhibited a core\u2010shell architecture, and demonstrated high loading efficiencies for QUR (93.1%\u2009\u00b1\u20092.56) and TAM (84.27\u2009\u00b1\u20093.66), with a mean particle diameter of approximately 135\u2009nm as determined by TEM. Behavioral assessment using Morris Water Maze revealed that lipopolysaccharide (LPS) administration impaired spatial learning and memory in rats; these effects were significantly ameliorated by QUR\/TAM\u2010Si@CsNPs treatment, to a greater extent than Si@CsNPs loaded individually with QUR or TAM. Biochemical, apoptotic, and histopathological analyses further demonstrated that treatment with QUR\/TAM\u2010Si@CsNPs normalized acetylcholinesterase activity, Tau protein level, \u03b2\u2010amyloid accumulation, pro\u2010inflammatory mediators, and apoptotic indices while preserving hippocampal architecture. Collectively, these findings demonstrate that QUR\/TAM\u2010Si@CsNPs exert combined anti\u2010inflammatory and neuroprotective effects, highlighting their promise as a multifunctional nanotherapeutic strategy against LPS\u2010associated neurodegenerative and AD\u2010like neuropathological alterations.<\/jats:p>","DOI":"10.1002\/jbm.b.70150","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T09:37:05Z","timestamp":1787391425000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multilayered Silica\u2010Core\/Chitosan\u2010Coated Nanostructures Co\u2010Delivering Tamoxifen and Quercetin Mitigate\n                    <scp>LPS<\/scp>\n                    \u2010Associated Neurodegenerative and Alzheimer's Disease\u2010Like Alterations"],"prefix":"10.1002","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6596-3156","authenticated-orcid":false,"given":"Bassma 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