Strong catalysis and novel copper-induced cell death enable copper-based nanozymes to present good bactericidal capacity against antibiotic-resistant pathogens, but their aspect of the balance between low ROS and low-dose antibacterial performance remains a significant challenge. Herein, an innovative copper/cerium (Cu/Ce)-doped metal-polyphenol network nanozyme (CCP) was synthesized for synergistically modulating the multi-enzymatic activities and enhancing methicillin-resistant Staphylococcus aureus (MRSA) eradication, where Cu and Ce individually decorated on carbon nanosheet skeleton. Benefited from the Cu/Ce dual-site structure, CCP exhibited remarkable multi-enzymatic (superoxide dismutase-, peroxidase-, glutathione peroxidase-, and nicotinamide adenine dinucleotide peroxidase-like) and •OH scavenging activities. While possessing negative surface charge and good biocompatibility, CCP displayed excellent antibacterial capability. With the addition of H2O2, CCP achieved complete killing against MRSA at 30 µg·mL− 1, whose process exhibited rather low ROS content, suggesting the balanced ability of CCP between peroxidase catalysis and ROS scavenging. Surprisingly, CCP could eradicate ~80% MRSA biofilms at 60 µg·mL− 1 without H2O2, probably attributed to the weak acidic, H2O2- and GSH-rich biofilm microenvironment for enhancing the peroxidase and glutathione peroxidase catalyses. Mechanism explorations revealed that the prominent antibacterial behavior was associated with the Cu/Ce synergistic effect on blocking bacterial cell membrane construction and cell wall biosynthesis, breaking ATP and protein synthesis, inducing protein toxicity stress and promoting TCA cycle to react with toxic Cu+/Ce3+ for cuproptosis-like death. Furthermore, shrimp preservation experiment demonstrated the great potential of CCP in food preservation field. This work paved a new avenue for future investigation of multifunctional Cu-based nanozymes.
Liang et al. (Thu,) studied this question.