An All-in-One Nanozyme for Synergistic Diabetic Wound Therapy: NIR-Augmented NO Release and Microenvironment Modulation

Diabetic wound infection remains a devastating threat to human health, largely due to bacterial colonization and increased antibiotic resistance during conventional treatments, and alternative therapeutic strategies are thus urgent to improve diabetic wound healing. Herein, we developed a multifaceted nanoplatform (CuO@SiO 2 @NO@Au, CSNA NPs) consisting of a cupric oxide (CuO) core, a mesoporous silicon nanoshell loaded with nitric oxide (NO), and in situ grown ultrasmall Au nanoparticles (NPs) for improved diabetic wound treatment. The results showed that the prepared CSNA NPs exhibited remarkable dual-enzyme mimic activity of glucose oxidase (GOx) and peroxidase (POD), effectively oxidizing glucose to generate gluconic acid, thereby reducing the glucose levels and reversing the acidic wound microenvironment. In addition, the fabricated nanoplatform generated abundant H 2 O 2 , which was converted into highly toxic hydroxyl radical ( · OH), leading to efficient bacterial eradication that was subsequently. Under near-infrared (NIR) light irradiation, the CSNA nanozyme also triggered the release of NO gas and aided in the removal of bacterial biofilms, collectively improving the wound microenvironment. By integrating chemodynamic therapy (CDT), photothermal therapy, and NO gas therapy, this self-activatable NIR- augmented nanozyme provides a promising antimicrobial strategy for diabetic wound treatment.