{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:55:35Z","timestamp":1790794535496,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371405"],"award-info":[{"award-number":["82371405"]}],"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"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Secondary neuroinflammation drives progressive damage after traumatic brain injury (TBI), but therapeutics that modulate key inflammatory amplifiers remain limited. Here, we identify infiltrating macrophages as the predominant TREM1\u2010expressing population in TBI human and mouse brain and show that TREM1 deletion attenuates neuroinflammation, preserves neurovascular integrity, and improves neurological and behavioral recovery after TBI. To develop a pharmacological strategy, we designed a de novo TREM1\u2010binding peptide, converted it into a mannose\u20106\u2010phosphate lysosome\u2010targeting chimera (LYTAC), and delivered it using an Angiopep\u20102\u2010functionalized, pH\u2010responsive dendrimer nanoparticle. This Angiopep\u20102\/PAMAM\/TPA\/LYTAC nanoparticle (APTL\u2010NP) enhanced brain delivery, promoted lesion\u2010responsive payload release, reduced TREM1 protein abundance in vivo, and outperformed free degrader and LP17 in suppressing inflammatory mediators, edema, blood\u2013brain barrier disruption, neuronal apoptosis, and behavioral deficits. Single\u2010cell transcriptomics suggested remodeling of myeloid, astrocytic, vascular, and SPP1\/CXCL\u2010associated communication programs. These findings support targeted TREM1 reduction as a strategy for modulating secondary TBI injury.<\/jats:p>","DOI":"10.1002\/advs.77972","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:00:31Z","timestamp":1790532031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["AI\u2010Designed TREM1\u2010Targeted LYTAC Nanoparticles Reprogram the Neuroimmune Microenvironment in Traumatic Brain Injury"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9600-1195","authenticated-orcid":false,"given":"Yimin","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology  Wuhan Hubei People's Republic of China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction Huazhong University of Science and Technology  Wuhan People's 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