pH-gated dual-modal switch photothermal cascade nanozyme hydrogel for diabetic infectious wound healing

Diabetic wounds are affected by hyperglycemia and neurovascular complications, and are often further exacerbated by bacterial infections, hypoxia, and insufficient collagen deposition. To overcome these pathological barriers, we have designed a pH-gated nanozyme cascade catalytic strategy for rapid bacterial eradication and skin regeneration. In this study, we first synthesized Prussian blue nanoparticles (PB NPs) with photothermal properties and peroxidase (POD)-/catalase (CAT)-like activities, which were then co-loaded with glucose oxidase (GOX) into an oxidized hyaluronic acid/carboxymethyl chitosan hydrogel. Multifunctional nanozyme hydrogel (PB/GOX-Gel) was constructed to control the microenvironment of diabetic wounds in a time sequence. Specifically, PB/GOX-Gel generates abundant hydroxyl radicals through photothermal therapy and the GOX/POD self-cascade reaction, thereby achieving potent antibacterial effects and lowering blood sugar levels during the initial treatment of diabetic-infected wounds. Furthermore, PB/GOX-Gel promotes the proliferation and remodeling phase of wound repair under neutral or weakly alkaline conditions by mitigating hypoxia and excessive oxidative stress through the GOX/CAT self-cascade reaction. Collectively, this pH-regulated dual-mode catalytic strategy can enhance antibacterial efficacy against S. aureus and E. coli, alleviate oxidative stress, improve oxygen supply, and thereby significantly accelerate diabetic wound repair. This strategy achieves whole-process treatment of diabetic-infected wounds, providing a promising therapeutic intervention for diabetic wound management.