Endogenous glucose-driven cascade reaction of nano-drug delivery for boosting multidrug-resistant bacteria-infected diabetic wound healing.

Multidrug-resistant (MDR) bacteria-infected wound healing remains greatly challenging, especially in diabetic patients. Herein, a novel nano-drug delivery based on endogenous glucose-driven cascade reaction is proposed for boosting MDR bacteria-infected diabetic wound healing with high efficacy by improving wound microenvironment and enhancing photodynamic antibacterial activity. The composite nanoagent is first self-assembled by integrating berberine (BBR) and epigallocatechin gallate (EGCG) from natural plant extracts, named as BE, which is successively coated with manganese dioxide nanoshells (MnO) and glucose oxidase (GOX) to form the final BEMG. The cascade reaction is triggered by glucose at the wound site of diabetes which is specifically catalyzed by GOX in the BEMG to produce gluconic acid and hydrogen peroxide (HO). That is subsequently to decompose MnO in the BEMG to generate oxygen (O). The BEMG as photosensitizers effectively produce reactive oxygen species (ROS) to enhance the eradication of bacteria with the assistance of O. Under the synergistic function of the cascaded reaction, the BEMG present excellent antibacterial efficacy even for MDR bacteria. The in vivo experiments explicitly validate that the constructed nano-drug delivery can augment the MDR bacteria-infected diabetic wound healing with excellent biosafety. The as-proposed strategy provides an instructive way to combat ever-threatening MDR bacteria, which particularly is beneficial for diabetic patients.