Glucose-activated nanozyme hydrogels for microenvironment modulation via cascade reaction in diabetic wound

Wound Healing in diabetic patients presents significant challenges due to heightened risks of bacterial infection, elevated glucose levels, and insufficient angiogenesis. Nanozymes are widely employed for wound healing, but most current nanozyme systems exhibit only moderate activity limited by incompatible reaction microenvironments including pH and hydrogen peroxide (H2O2) concentration. Herein, a glucose-activated nanozyme hydrogel was developed using bovine serum albumin (BSA)-modified gold nanoparticles (Au NPs) attached to a two-dimensional (2D) metal-organic framework (MOF) (Cu-TCPP(Fe)@Au@BSA) by an in situ growth method. The Au NPs function as a glucose oxidase (GOx)-like enzyme, converting glucose to gluconic acid and H2O2, triggering the peroxidase (POD)-like activity of Cu-TCPP(Fe) to produce hydroxyl radicals (•OH), effectively eliminating bacteria. Additionally, the modification of BSA reduces the Au NP size, enhancing enzyme activity. Both in vitro and in vivo tests demonstrate that this nanozyme hydrogel can be activated by the microenvironment to lower blood glucose, eliminate bacterial infections, and promote epithelial formation and collagen deposition, thus accelerating diabetic wound healing effectively. The multifunctional nanozyme hydrogel dressing developed in this study presents a promising therapeutic approach to enhance diabetic wound healing.