Electron Reservoir MoO_3–x-Driven Cu⁺ Doped Nanozyme with Enhanced Antibacterial Activity via Disrupting Redox Homeostasis

Redox nanozymes offer an appealing reactive oxygen species (ROS)-based antibacterial strategy via disrupting intracellular homeostasis, however, they still face many obstacles such as low enzymic activity and irreversible loss of catalytic active center. Meanwhile, the antioxidant glutathione (GSH) overexpressed in infected sites would limit the therapy efficiency. Herein, we develop a multifunctional nanozyme based on copper(I) (Cu⁺) ion doped MoO_3–x (Cu⁺-MoO_3–x) by a simple yet efficient oxygen vacancy-reduced strategy without any pretreatment or additional agents. The resultant Cu⁺-MoO_3–x hybrid possesses enhanced peroxidase-like (POD-like) activity, rapid GSH-depleting function and biodegradable ability. It can achieve highly efficient elimination of Pseudomonas aeruginosa (P. aeruginosa) via disrupting cellular redox balance. More intriguingly, GSH-depleting redox reaction between Cu⁺-MoO_3–x and GSH could translate Mo⁶⁺ into Mo⁵⁺, thereby leading to partial recovery of POD-like activity of Cu⁺-MoO_3–x hybrid for continuous ^∙OH generation. In vitro and in vivo experiments demonstrated that Cu⁺-MoO_3–x hybrid had stronger antibacterial property compared to MoO_3–x by rapid GSH consumption and plentiful ^∙OH generation without providing extra H₂O₂, as well as neglective toxicity to healthy organs. In view of its remarkable enzymic activity and good biosafety, the developed Cu⁺-MoO_3–x redox nanozyme can be used as a promising antimicrobial for P. aeruginosa infection.