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In this study, we designed a microglial membrane\u2010wrapped single\u2010atom nanozyme (PtRhIr\/Ru SAN@M) by anchoring a single atom of Ru onto ultrasmall, medium\u2010entropy PtRhIr alloys. This design integrates two underutilized strategies, single\u2010atom nanozymes (SANs) and medium\u2010entropy catalysts, to address critical therapeutic gaps in ICH therapy. PtRhIr\/Ru SAN@M exhibited enhanced catalytic activity with superior Hydroxyl radical (\u2022OH) scavenging and superoxide dismutase (SOD)\u2010like and catalase (CAT)\u2010like performances compared to Ru\u2010free PtRhIr@M, enabled by electronically modulated active sites. Fluorescence imaging confirmed its ability to penetrate the blood\u2010brain barrier (BBB) and accumulate in post\u2010ICH neuroinflammatory regions. Both in vitro and in vivo experiments demonstrated that PtRhIr\/Ru SAN@M repolarized microglia from the M\n 1<\/jats:sub>\n to the M\n 2<\/jats:sub>\n phenotype, disrupting the neuroinflammatory cycle and halting neuronal death. Therapeutic intervention with PtRhIr\/Ru SAN@M significantly increased survival rates, restored neurological function, and enhanced spatial memory after ICH. This study pioneers the integration of SANs with medium\u2010entropy alloys for ICH, offering a dual\u2010target ROS\u2010inflammation regulatory strategy and a generalizable platform for ROS\u2010related degenerative disease therapies.\n <\/jats:p>","DOI":"10.1002\/advs.202520714","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T04:04:47Z","timestamp":1767585887000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Microglial Membranes Wrapped Ultrasmall Medium\u2010Entropy Ru Single\u2010Atom Nanozyme: Enhanced Catalysis for Accelerating Inflammation\/Redox Microenvironment Regulation in Intracerebral Hemorrhage"],"prefix":"10.1002","volume":"13","author":[{"given":"Jiebo","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Neurosurgery Research Institute The First Affiliated Hospital Fujian Medical University Fuzhou Fujian 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