Intracerebral hemorrhage (ICH) causes severe secondary brain injury (SBI) through excessive inflammation and reactive oxygen species (ROS), and current treatments lack effective dual-target efficacy. In this study, we designed a microglial cell membrane-coated single-atom nanozyme (PtRhIr/Ru SAN@M) by anchoring a Ru atom on an ultra-small, medium-entropy PtRhIr alloy. This design integrates two underutilized strategies—single-atom nanozymes (SANs) and medium-entropy catalysts.To address the critical therapeutic gap in ICH treatment. PtRhIr/Ru SAN@M, based on electronically modulated active sites, has superior hydroxyl radical (•OH) scavenging capacity and exhibits superoxide dismutase (SOD)- and catalase (CAT)-like activity, all outperforming PtRhIr@M. Fluorescence imaging confirmed that it can penetrate the blood-brain barrier (BBB) and accumulate in neuroinflammatory regions after ICH. Both in vitro and in vivo experiments indicate that PtRhIr/Ru SAN@M repolarizes microglia from the M1 to the M2 phenotype, disrupts the neuroinflammatory cycle, and prevents neuronal death.Therapeutic intervention with PtRhIr/Ru SAN@M significantly improved survival rates, restored neurological function, and enhanced spatial memory after ICH. This study pioneeringly integrates SANs with medium-entropy alloys for ICH, providing a dual-target ROS inflammation regulation strategy and a potentially translatable platform for treating ROS-related degenerative diseases.

Reference News：

https://www.x-mol.com/paper/2008217982698962944/t?adv