Cascade ROS-modulating Au/Cu nanozyme hydrogel with nitric oxide release ability for accelerated diabetic foot ulcer healing.

Diabetic foot ulcers (DFUs) persist due to excessive reactive oxygen species (ROS), infection, and poor angiogenesis. We engineered an injectable guar gum hydrogel (AuCu-Arg/Gel) embedding gold/copper nanozymes (Au@Cu₂(OH)₃Cl-L-Arg) to address these barriers synergistically. The nanozymes display cascade-mimicking peroxidase, superoxide dismutase, and catalase activities to rebalance ROS. In the acidic, bacteria-laden niche, peroxidase-like activity is switched on, generating hydroxyl radicals (•OH) and driving bacterial viability to < 1 %. Concurrently, the ROS-rich milieu triggers nitric oxide (NO) release from L-arginine (2.93 μM in 10 min), upregulating VEGF and neovascularization. Mild near-infrared (NIR) photothermal heating (1.5 W cm⁻², 5 min) increased the apparent POD-like initial rate 1.94-fold vs no-NIR (see Fig. 2 A). without tissue injury. In diabetic rats, AuCu-Arg/Gel plus NIR accelerated wound closure, dampened inflammation, and increased collagen deposition and vascular density. The results confirmed day-12 residual wound areas to 2.1 % (AuCu-Arg/Gel + NIR). This spatiotemporally programmable platform integrates ROS modulation, on-demand antibacterial action, NO gas therapy, and photothermal enhancement for chronic wound management.