Natural enzyme cascade bimetallic sulfide MoCuSx nanozyme for synergistic photothermal/photodynamic enhanced chemodynamic antimicrobial therapy of wound infection

Chemodynamic therapy (CDT) involving highly toxic hydroxyl radical (•OH) with no drug resistance has gained widespread attention for antibacterial applications. However, the CDT effect is seriously confined by overexpressed glutathione (GSH) and limited hydrogen peroxide (H 2 O 2 ) in the infection sites. Here, we have constructed a cascade enzyme/nanozyme assembly (MCS/GOx) composing of a bimetallic sulfide MoCuS x (MCS) nanozyme loaded with natural glucose oxidase (GOx) for synergistic photothermal/photodynamic enhanced chemodynamic antimicrobial therapy with high performance. The loaded GOx can promote the peroxidase (POD)-like activity of MCS by providing an acidic microenvironment and self-supplying H 2 O 2 , achieving cascade generation of •OH for efficient CDT. The CDT effect can be further promoted by a co-catalysis mediated by the Mo 4+ /Mo 6+ redox couple. Upon exposure to an 808 nm near-infrared laser, MCS/GOx provides hyperpyrexia for photothermal antibacterial therapy (PTT), and produce singlet oxygen ( 1 O 2 ) for photodynamic therapy (PDT). Moreover, MCS/GOx can significantly consume antioxidant glutathione via the Cu + /Cu 2+ redox couple and PDT-mediated 1 O 2 production, thereby enhancing CDT antibacterial effect. In vitro experiments exhibit that MCS/GOx has combined antimicrobial effect against Staphylococcus aureus and Escherichia coli . Further in vivo studies demonstrate that MCS/GOx can efficiently eliminate bacterial cells in wound tissues and accelerate wound healing with low inflammatory response and good biosafety. Consequently, the proposed MCS/GOx with multiple bactericidal modalities shows a great potential in fighting wound infections.