Glucose‐Activated Fe‐Cu Dual‐Ion Nanozyme Cascade Reactor with Photothermal Enhancement for Antimicrobial Therapy in Diabetic Wound Healing

Nanozyme technology offers promising avenues for the development of new antibacterial agents to combat antibiotic resistance. However, the antibacterial efficacy of nanozymes is constrained by their dependence on hydrogen peroxide (H2O2). In this study, a glucose-activatable nanoreactor (FCSGP NPs) with high antimicrobial efficiency and drug loading ability is designed to enhance the anti-infection effects in diabetic wound healing. Under hyperglycemic conditions, this nanoreactor initiates a sequential cascade reaction by consuming glucose, thereby amplifying the anti-infective effects. The glucose oxidase (GOx)-mediated glucose oxidation cascade produces both H2O2 (for the Fenton reaction) and gluconic acid (for pH modulation), synergistically enhancing chemodynamic therapy (CDT). The resulting acidic microenvironment accelerates the FCSGP nanoreactor degradation, triggering the glutathione (GSH)-induced release of Fe and Cu ions, which subsequently catalyze a Fenton-like reaction with H2O2 to generate a highly reactive hydroxyl radical (•OH). Furthermore, the FCS-mediated photothermal (PTT) effect induces localized hyperthermia, which simultaneously enhances the GOx enzymatic activity and enables synergistic PTT-CDT. This combined action eradicates biofilm-associated infections in the absence of exogenous H2O2 while accelerating diabetic wound healing. By leveraging these synergistic cascade reactions, this endogenous enzyme-based strategy offers a promising platform for enhancing diabetic wound healing.