Specific Peroxidase-like Nanozyme with Boosted Activity at Neutral pH for Antibacterial Application

Peroxidase (POD)-like nanozymes have been developed for antibacterial purposes. However, for chronic wounds, the antibacterial efficiency was limited due to the pH mismatch between the optimal activity of POD-like nanozyme (acidic condition) and bacterial infection microenvironment (BIME) (neutral condition) and even the multienzymatic activity to suppress the level of reactive oxygen species. Herein, Cu-His, synthesized through Cu 2+ coordinating with l -histidine (His) in NaOH, exhibited POD-like activity at neutral pH but not catalase- and oxidase-like activity. As a specific POD-like nanozyme, Cu-His could directly catalyze the oxidation of TMB (as a substrate) by H 2 O 2 to orange oxTMB 2+ (releasing two electrons) and concurrently greatly elevate the level of produced •OH, demonstrating boosted catalytic activity. Though simulating endogenous H 2 O 2 concentrations and neutral pH in BIME, Cu-His nanozyme demonstrated highly efficient antibacterial activity against both Gram-negative bacteria ( Escherichia coli ) and Gram-positive bacteria ( Staphylococcus aureus ). Finally, in vivo antibacterial therapy against S. aureus was also achieved through the Cu-His nanozyme efficiently catalyzing endogenous H 2 O 2 in BIME, presenting a promising antibacterial therapeutic perspective.