Glucose-Oxidase Conjugated Cerium Oxide-Based Super Nanozyme for Rapid MRSA Eradication and Wound Closure.

The global rise of antibiotic-resistant pathogens poses a serious challenge to public health, particularly in the healing of infected chronic wounds. Innovative, safe, and therapeutically adaptive strategies are urgently required to combat antimicrobial resistance (AMR) pathogens. A glucose-oxidase conjugated cerium oxide nanoparticle (CeO2 NPs-GOx)-based nanozyme displaying oxidase-mimetic activity at physiological pH and wound exudate is developed. The conjugate displays potent antibacterial activity and eradication of β-lactamase-producing clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) by producing superoxide and hydroxyl radicals in the presence of adenosine triphosphate (ATP) and glucose. Microscopic imaging, lactate dehydrogenase (LDH) release and lipid peroxidation assays revealed compromised bacterial cell wall structure and release of cytoplasmic contents due to the continuous production of free radicals. The in vivo MRSA-infected wound data showed that application of CeO2 NPs-GOx led to infection clearance within a week, as well as better wound closure than vancomycin. Upon CeO2 NPs-GOx treatment, wound tissues undergo enhanced re-epithelialization, collagen deposition, and angiogenesis, while reduced production of pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β). CeO2 NPs-GOx exposure displayed almost no accumulation rather rapid clearance of nanozymes from the body. Overall, this study establishes CeO2 NPs-GOx as an effective antibacterial nanozyme, integrating ATP-assisted oxidase-mimetic activity, exhibiting reactive oxygen species (ROS)-mediated elimination of MRSA infection from wounds. Thus, the developed novel CeO2 NPs-based nanozyme offers an alternative to antibiotics for clinical translation and effective control of AMR spread.