Glucose Oxidase-Integrated Metal-Polyphenolic Network as a Microenvironment-Activated Cascade Nanozyme for Hyperglycemic Wound Disinfection

The high systemic blood glucose concentration of hyperglycemic wound microenvironment (WME) severely impedes the disinfection and healing of infected skin wounds. Herein, a WME-activated smart natural product, integrated GOx-GA-Fe nanozyme (GGFzyme), is engineered, which combines a nanozyme and natural enzyme to promote reactive oxygen species (ROS) generation in situ for hyperglycemic wound disinfection. GGFzyme can consume a high concentration of glucose in hyperglycemia wounds and generate H₂O₂. The conversion of glucose into gluconic acid not avails starvation treatment but reduces the pH of WME to elevate the catalytic activities of both the nanozyme (GA-Fe) and natural enzyme (GOx). And H₂O₂ is then high efficiently catalyzed into ^•OH and O₂^•- in situ to combat pathogenic bacteria and promote wound disinfection. The high catalytic antibacterial capacity and superior biosafety, combined with beneficial WME modulation, demonstrate that GGFzyme is a promising therapeutic agent for hyperglycemic wounds.