A Copper Single-Atom Cascade Bionanocatalyst for Treating Multidrug-Resistant Bacterial Diabetic Ulcer

摘要

Diabetic ulcers induced by multidrug-resistant (MDR) bacteria have severelyendangered diabetic populations. These ulcers are very challenging to treatbecause the local high glucose concentration can both promote bacterialgrowth and limit the immune system’s bactericidal action. Herein, a glucoseoxidase-peroxidase (GOx-POD) dual-enzyme mimetic (DEM) bionanocatalyst,Au@CuBCats is synthesized to simultaneously control glucose concentrationand bacteria in diabetic ulcers. Specifically, the AuNPs can serve as GOxmimics and catalyze the oxidation of glucose for the formation of H_2O_2; theH_2O_2 can then be further catalytically converted into OH via thePOD-mimetic copper single atoms. Notably, the unique copper single atomscoordinated by one oxygen and two nitrogen atoms (CuN_2O_1) exhibit betterPOD catalytic performance than natural peroxidase. Further DFT calculationsare conducted to study the catalytic mechanism and reveal the advantage ofthis CuN_2O_1 structure as compared to other copper single-atom sites. Both invitro and in vivo experiments confirm the outstanding antibacterialtherapeutic efficacy of the DEM bionanocatalyst. This new bionanocatalystwill provide essential insights for the next generation of antibiotic-freestrategies for combating MDR bacterial diabetic ulcers, and also offerinspiration for designing bionanocatalytic cascading medicines.