Inverse Oxide/Alloy-Structured Nanozymes with NIR-Triggered Enzymatic Cascade Regulation of ROS Homeostasis for Efficient Wound Healing.

The precise spatiotemporal control of reactive oxygen species (ROS) generation and scavenging remains pivotal for infected wound healing. However, conventional nanozymes fail to adaptively regulate ROS dynamics across inflammatory and proliferative phases. A near-infrared (NIR)-activated inverse oxide/alloy-structured nanozyme (CoFe/ZnO@C) is developed, featuring enzymatic cascade activities to tune ROS homeostasis through synergistic chemodynamic (CDT), photodynamic (PDT), and photothermal (PTT) therapies. The nanozyme orchestrates a self-regulated cascade: peroxidase (POD)-like activity initially generates bactericidal hydroxyl radicals in acidic wounds, while subsequent NIR triggers hot electron transfer from CoFe to ZnO, facilitating synchronized superoxide dismutase (SOD)-like, catalase (CAT)-like and hydroxyl radical antioxidant capacity (HORAC) activities to scavenge residual ROS. This cascaded network dynamically balances ROS production (POD) and scavenging (NIR-driven SOD/CAT/HORAC), eradicating bacteria while resolving inflammation. In vitro/vivo studies have shown that the proposed method for maintaining ROS homeostasis can markedly enhance the rate of wound healing by the regulation of the inflammatory environment within the injured tissue and the facilitation of rapid re-epithelialization. This work provides an intelligent nanozyme platform that simulates the function of natural enzymes and constructs a cascade reaction strategy to balance the antibacterial and anti-inflammatory demands in the wound microenvironment.