Spin-state engineering of nanozymes to boost ROS generation for accelerated wound healing

• Spin-State Engineering via Cu Doping: Cu doping in CoOOH nanozymes successfully modulates the Co sites from a low-spin (LS) state to an intermediate-spin (IS) state through d-d orbital interactions. • Enhanced ROS Generation and Activity Shift: The spin-state transition (LS to IS) significantly boosts Reactive Oxygen Species (ROS) production and shifts the dominant catalytic pathway from intrinsic catalase-like (CAT-like) activity in CoOOH to peroxidase-like (POD-like) activity in CuCoOOH. • Synergistic Light Enhancement: Under visible light irradiation, CuCoOOH enhances photogenerated electron transfer within the POD reaction (boosting • OH) and additionally photocatalytically generates O 2 •− and 1 O 2 , achieving highly efficient multi-ROS production. • Exceptional Antibacterial Efficacy: The CuCoOOH/H 2 O 2 /light system demonstrates outstanding antibacterial performance, achieving > 99.999 % eradication of drug-resistant ESBL-producing E. coli both in vitro and in an infected wound model. • Accelerated Wound Healing with Biocompatibility: The engineered CuCoOOH nanozyme effectively promotes angiogenesis, reduces inflammation, accelerates wound healing in vivo, and exhibits excellent biocompatibility. Despite nanozymes’ promise against drug-resistant bacteria, their activity control remains trial-and-error based with unclear intrinsic catalytic mechanisms. Herein, a facile Cu doping converted spin-state transition approach is reported for explores the structure–activity relationship between the electronic states of active sites and enzymatic functionality in CoOOH nanozymes. Experimental analyses demonstrate that Cu doping effectively modulates Co sites from a low-spin (LS) to an intermediate-spin (IS) state. The engineered CuCoOOH nanozyme features abundant oxygen vacancies and substantial lattice distortion, which cooperatively facilitate electron transfer from the d xy to d z 2 orbital. This spin electron rearrangement critically optimizes enzymatic performance, shifting the dominant catalytic pathway from intrinsic catalase-like (CAT-like) activity in CoOOH to peroxidase-like (POD-like) activity in CuCoOOH. Under visible-light irradiation, the CuCoOOH system not only enhances photogenerated electron transfer within the POD reaction to boost hydroxyl radical ( • OH) production but also photocatalytic generation of superoxide anion radicals (O 2 •- ) and singlet oxygen ( 1 O 2 ), thereby achieving high-efficiency reactive oxygen species (ROS) production. Biological evaluations confirm exceptional antibacterial efficacy (>99.999 % eradication rate) against drug-resistant pathogens, coupled with excellent biocompatibility, suggesting the therapeutic potential for infections by drug-resistant bacteria.