An NIR-II-Enhanced Nanozyme to Promote Wound Healing in Methicillin-resistant Staphylococcus Aureus Infections

Deep tissue bacterial infections, especially methicillin-resistant Staphylococcus aureus (MRSA) infections, pose challenges to clinical therapy due to their low debridement efficiency and relapsing. Molybdenum disulfide (MoS2) is used in the antibacterial field as a classic photothermal agent (NIR-I) with good biocompatibility. However, due to its limited NIR-I tissue penetration ability and single treatment mode, MoS2 has poor therapeutic effects on deep tissue infection. Herein, we prepared a defect-type hybrid 2H-MoS2 nanozyme (MoWS2) using hydrothermal method fabricate the MoWS2 composite, which is a new antibacterial strategy involving photothermal and enzyme catalysis, and further enhances the activity of the nanozyme through overheating. The regulation of 2H-MoS2 defects through tungsten ion doping endows MoWS2 with better near-infrared two-region absorption (NIR-II) and enzyme catalytic performance. Antibacterial activity experiments in vitro have shown that MoWS2 can achieve efficient bactericidal activity and biofilm clearance through hyperthermia and reactive oxygen species (ROS). Deep MRSA infection experiments have shown that MoWS2 rapidly removes bacteria from subcutaneous infected tissues through photothermal therapy (PTT) and chemodynamic therapy (CDT), accelerates the dissipation of abscesses, and promotes the healing of infected wounds. Additionally, the versatile treatment mode of MoWS2 was further confirmed through tissue sectioning and immunofluorescence staining analysis. Overall, these results provide a feasible approach for achieving efficient treatment of deep tissue infections through tungsten ion doping to regulate defective 2H-MoS2. STATEMENT OF SIGNIFICANCE: The photothermal effect of MoS2 nanosheets in the NIR-I (650-900 nm) window in anti-MRSA therapy is considered to be highly reliable and efficient in PTA. However, most of the developed PPT therapies or antimicrobial systems based on PTT therapies developed with 1T-MoS2 have in vivo sterilization temperatures of more than 55°C, which have the risk of damaging the normal tissues of the skin. In this study, we prepared W@MoS2 with a good photothermal effect (36.9%) in the NIR-II window and good peroxidase-like activity. The combined effect of PTT and CDT has a stronger bactericidal effect while avoiding high-temperature damage, which makes the W@MoS2 material more advantageous in terms of antimicrobial effect.