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

Abstract Diabetic ulcers induced by multidrug‐resistant (MDR) bacteria have severely endangered diabetic populations. These ulcers are very challenging to treat because the local high glucose concentration can both promote bacterial growth and limit the immune system's bactericidal action. Herein, a glucose oxidase‐peroxidase (GOx‐POD) dual‐enzyme mimetic (DEM) bionanocatalyst, Au@CuBCats is synthesized to simultaneously control glucose concentration and bacteria in diabetic ulcers. Specifically, the AuNPs can serve as GOx mimics and catalyze the oxidation of glucose for the formation of H 2 O 2 ; the H 2 O 2 can then be further catalytically converted into OH via the POD‐mimetic copper single atoms. Notably, the unique copper single atoms coordinated by one oxygen and two nitrogen atoms (CuN 2 O 1 ) exhibit better POD catalytic performance than natural peroxidase. Further DFT calculations are conducted to study the catalytic mechanism and reveal the advantage of this CuN 2 O 1 structure as compared to other copper single‐atom sites. Both in vitro and in vivo experiments confirm the outstanding antibacterial therapeutic efficacy of the DEM bionanocatalyst. This new bionanocatalyst will provide essential insights for the next generation of antibiotic‐free strategies for combating MDR bacterial diabetic ulcers, and also offer inspiration for designing bionanocatalytic cascading medicines.