Hollow CuS nanocubes loaded with defective Co-LDHs as efficient antibacterial nanozymes against drug-resistant pathogens.

The overuse of antibiotics has given rise to a substantial number of drug-resistant bacteria, posing a grave threat to human health. Developing non-antibiotic therapeutic agents featuring high efficiency and low drug resistance represents a promising strategy for combating drug-resistant bacteria. This study designs a nanozyme material, CuS-Co-LDHs, by loading defective cobalt hydroxide nanosheets (Co-LDHs) onto the surface of hollow copper sulfide (CuS) nanocubes, enabling efficient sterilization through peroxidase activity. Compared with pure CuS, the maximum reaction velocity (Vmax) and specific peroxidase-like activity of this composite material for hydrogen peroxide were increased by 2.3 times.Spectroscopic analyses revealed that defect-induced oxygen vacancies drive directional interfacial electron transfer (Co-LDHs→CuS), accelerating the rate-limiting Cu2 +→Cu+ Fenton-like redox cycle. In vitro antibacterial experiments showed that the inhibition ratios of CuS-Co-LDHs against Pseudomonas aeruginosa and Staphylococcus aureus reached 76.14% and 69.8%, respectively. Cellular-level evaluations further confirmed that active ·OH generation induced a 1 -2log10 reduction in viable bacterial counts, accompanied by severe intracellular oxidative stress and physical cell membrane disruption.In vivo experiments demonstrated that after 7 days of treatment, the wound healing ratios of the experimental group of mice with bacterial infections reached 86%, significantly higher than that of the control group (47%).Histological and immunohistochemical analyses demonstrated significant downregulation of pro-inflammatory cytokines (TNF-αandIL-6), robust CD31-positive neovascularization, and dense, orderly collagen matrix deposition. This enhanced antibacterial activity originated from the synergistic effect of CuS and Co-LDHs in the catalytic decomposition of hydrogen peroxide. This study not only provides a strategy for the design of antibacterial nanomaterials but also offers an approach to addressing the problem of bacterial resistance.Overall, this work not only offers an effective non-antibiotic platform for drug-resistant wound care but also highlights the broader potential of defect-engineered heterojunction nanozymes in chemodynamic therapeutics.