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The effective blood\u2010brain barrier (BBB) penetration and brain delivery of antioxidative agents remain the biggest challenge in treating ischemic reperfusion\u2010induced cerebrovascular and neural injury. In this study, a metal\u2010organic framework (MOF) nanozyme (MIL\u2010101\u2010NH\n                    <jats:sub>2<\/jats:sub>\n                    (Fe\/Cu)) with ROS scavenging activities to encapsulate neuroprotective agent rapamycin is fabricated and decorating the exterior with BBB\u2010targeting protein ligands (transferrin), thereby realizing enhanced drug retention and controlled release within ischemic lesions for the synergistic treatment of IS. Through the receptor\u2010mediated transcellular pathway, the transferrin\u2010coated MOF nanoparticles achieved efficient transport across the BBB and targeted accumulation at the cerebral ischemic injury site of mice with middle cerebral artery occlusion\/reperfusion (MCAO\/R), wherein the nanocarrier exhibited catalytic activities of ROS decomposition into O\n                    <jats:sub>2<\/jats:sub>\n                    and H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    \u2010responsive rapamycin release. By its BBB\u2010targeting, antioxidative, anti\u2010inflammatory, and antiapoptotic properties, the MOF nanosystem addressed multiple pathological factors of IS and realized remarkable neuroprotective effects, leading to the substantial reduction of cerebral infarction volume and accelerated recovery of nerve functions in the MCAO\/R mouse model. This MOF\u2010based nanomedicine provides valuable design principles for effective IS therapy with multi\u2010mechanism synergies.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202402376","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T07:40:17Z","timestamp":1728286817000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Blood\u2010Brain Barrier\u2010Penetrating Metal\u2010Organic Framework Antioxidant Nanozymes for Targeted Ischemic Stroke Therapy"],"prefix":"10.1002","volume":"14","author":[{"given":"Qing","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery Zhongnan Hospital of Wuhan University School of Pharmaceutical Sciences Wuhan University  Wuhan 430071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Wang","sequence":"additional","affiliation":[{"name":"Central Laboratory Renmin 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