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Unfortunately, current medications cannot effectively ameliorate the secondary injury at traumatic sites. Here, it is reported that intrinsically bioactive multifunctional nanocomposites (ANG\u2010MnEMNPs\u2010Cur, AMEC) mediate antioxidation and anti\u2010neuroinflammation for targeted TBI theranostics, which are engineered by loading the neuroprotective agent curcumin on angiopep\u20102 functionalized and manganese doped eumelanin\u2010like nanoparticles. After intravenous delivery, efficient AMEC accumulation is observed in lesions of TBI mice models established by controlled cortical impact method, evidenced by <jats:italic>T<\/jats:italic><jats:sub>1<\/jats:sub>\u2013<jats:italic>T<\/jats:italic><jats:sub>2<\/jats:sub> magnetic resonance and photoacoustic dual\u2010modal imaging. Therapeutically, AMEC effectively alleviates neuroinflammation, protects blood\u2013brain barrier integrity, relieves brain edema, reduces brain tissue loss, and improves the cognition of TBI mice. Mechanistically, following the penetration into the traumatic tissues via angiopep\u20102 mediated targeting effect, the efficacy of AMEC is synergistically improved by combined functional moieties of curcumin and eumelanin. This is achieved by the alleviation of oxidative stress, inhibition of neuroinflammation via M1\u2010to\u2010M2 macrophage reprogramming, and promotion of neuronal regeneration. The as\u2010developed AMEC with well\u2010defined mechanisms of action may represent a promising targeted theranostics strategy for TBI and other neuroinflammation\u2010associated intracranial diseases.<\/jats:p>","DOI":"10.1002\/adhm.202200517","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T06:10:13Z","timestamp":1655100613000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Intrinsically Bioactive Manganese\u2013Eumelanin Nanocomposites Mediated Antioxidation and Anti\u2010Neuroinflammation for Targeted Theranostics of Traumatic Brain Injury"],"prefix":"10.1002","volume":"11","author":[{"given":"Duo","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine Daping Hospital Army Medical University  Chongqing 400042 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