Electron‐Deficient Effect Modulates Catalase‐Like Activity of Iron‐Nitrogen‐Carbon Nanozymes for Inflammatory Wound Therapy

Abstract Dual‐metal atom nanozymes (DANs) are frontier nanocatalysts that mimic natural enzymes to regulate the level of reactive oxygen species (ROS) in pathological tissue. However, the construction of DANs is mostly based on trial‐and‐error strategy rather than rational design due to their ambiguous catalytic mechanism. Herein, a promising strategy to construct highly efficient FeZn‐NC DANs by “electron‐deficient effect” for ROS scavenging is proposed. Redox‐inert Zn‐N 4 sites and axial N atom induce electron‐deficient Fe sites based on different electronegativity to accelerate catalase (CAT)‐like reaction. Besides, FeZn‐NC mimics superoxide dismutase (SOD) relying on the cyano‐group conjugated with the π‐system in the carbon carrier. Enhanced CAT‐like activity from Fe sites and SOD‐like activity from carbon carriers enabled FeZn‐NC more effective in mitigating cellular damage and inducing the phenotypic transformation of macrophages in acute inflammatory wounds. This work establishes more precise structure‐activity relationships for CAT and SOD mimics and provides a paradigm for the treatment of inflammation‐related diseases by catalytic therapy.