Bimetallic oxide Cu-Fe3O4 nanoclusters with multiple enzymatic activities for wound infection treatment and wound healing

Infections and oxidative stress complicate wound healing. In recent years, nanomaterials with natural en-zymatic activities have enabled the development of new antibacterial pathways. In this study, Cu-Fe3O4 nanoclusters with multienzyme properties were synthesized. Interestingly, they exhibited activity similar to that of horseradish peroxidase (POD) in acidic environments but their functions resembled superox -ide dismutase and catalase in neutral or weakly alkaline environments. In vitro studies have demonstrated the good free-radical scavenging activity of Cu-Fe3O4 nanoclusters in a neutral environment. Under acidic conditions, Cu-Fe3O4 nanoclusters combined with H2O2 demonstrated good antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli ( E. coli ). The combination of Cu- Fe3O4 and H2O2 was found to be effective in preventing MRSA infections and promoting wound healing in animal models. RNA sequencing (RNA-seq) technology revealed that chemodynamic therapy (CDT) us-ing nanoparticles can interfere with metabolic processes such as galactose metabolism in MRSA bacteria, destroy the transport system on the surface of MRSA, and affect quorum sensing to hinder the forma-tion of biofilms, thus achieving effective antibacterial efficacy. The use of Cu-Fe3O4 nanoclusters as a novel class of multi-catalytically active nanozymes in the anti-infection of disease-causing pathogens and wound healing has significant potential.Statement of significanceCu-Fe3O4 nanoclusters with multienzyme properties were successfully prepared by a solvothermal method. Cu-Fe3O4 nanoclusters exhibited horseradish peroxidase (POD)-like activity in acidic environ-ments and also showed synergistic effects similar to superoxide dismutase peroxidase in neutral or weakly basic environments. More importantly, these Cu-Fe3O4 nanoclusters showed high biosafety with no apparent in vivo toxicity. Chemodynamic therapy (CDT) using Cu-Fe3O4 nanoclusters was revealed by RNA sequencing (RNA-Seq) technology to interfere with the metabolic processes of MRSA bacteria, such as galactose metabolism, disrupt the MRSA surface transport system, and impede biofilm formation, re-sulting in effective antibacterial efficacy. The use of Cu-Fe3O4 nanoclusters for anti-infection and wound healing of pathogenic pathogens has significant potential as a novel class of multi-catalytic active nan-oclusters.(c) 2023 Published by Elsevier Ltd on behalf of Acta Materialia Inc.