Glucose-triggered self-perpetuating catalytic cascade in GOx@CuO2 nanoreactors for treating bacteria-infected diabetic wounds

The hyperglycemic microenvironment of diabetic wounds is highly susceptible to bacterial infection, persistent inflammation, and impaired angiogenesis, severely delaying the healing process. To overcome the limitations of current therapeutic strategies, this study innovatively developed an intelligent cascade nanoreactor, GOx@CuO 2 , which utilizes excess glucose (Glu) as a driving force. The key innovation of this system is its exploitation of the excess glucose at the lesion site. Catalyzed by glucose oxidase (GOx), the Glu is converted into gluconic acid and hydrogen peroxide (H 2 O 2 ) which simultaneously accomplishes the tripartite microenvironmental modulation of Glu depletion, acid production, and H 2 O 2 supply. Under acidic conditions, GOx@CuO 2 exhibits efficient peroxidase-like (POD-like) activity, catalyzing the generation of hydroxyl radicals (·OH) to achieve potent antibacterial effects. As glucose is gradually consumed and the pH increases, GOx@CuO 2 intelligently switches to a catalase-like (CAT) mode, decomposing residual H 2 O 2 into oxygen (O 2 ). This alleviates oxidative stress and promote angiogenesis, forming an adaptive synergistic therapeutic cycle of “antibacterial-promoting healing”. In vivo experiments confirmed that the nanoreactor significantly improved the wound microenvironment, achieving a wound closure rate of 93.4 % within 14 days. This study not only proposes a novel non-antibiotic therapeutic strategy responsive to the lesion microenvironment but also provides new insights for designing intelligent enzyme-catalyzed systems for tissue repair related to metabolic diseases.