Copper-manganese bimetallic oxide-encapsulated hydrogels with multienzyme activities accelerate MRSA-infected wound healing by disrupting bacterial protein expression.

Wound therapy for pathogenic infections remains a medical challenge worldwide. Nanozyme-based catalytic therapy provides a new therapeutic strategy for combating drug-resistant bacterial infections. However, its limited catalytic activity, nonlethal death mechanism, and imperfect wound repair capacity restrict its further development. In this work, a temperature-sensitive Cu_1.5Mn_1.5O₄/F127 hydrogel was prepared by encapsulating Cu_1.5Mn_1.5O₄ nanospheres (Cu_1.5Mn_1.5O₄ NSs) with multienzyme activities and photothermal properties in F127. The obtained hydrogel possesses oxidase-like (OXD-like), peroxidase-like (POD-like) and glutathione peroxidase-like (GSH-Px-like) activities, achieving efficient sterilization through the synergistic effects of reactive oxygen species (ROS), photothermal effects and glutathione depletion ability. Moreover, the hydrogel can slowly release copper and manganese ions at the wound site, accelerating wound healing by promoting collagen deposition and angiogenesis. Further prokaryotic RNA sequencing (RNA-seq) analysis revealed that the efficient bactericidal ability of the Cu_1.5Mn_1.5O₄/F127 hydrogel is due mainly to its ability to disrupt bacterial cell wall functions and affect protein expression and nucleotide metabolic pathways. In vivo experiments confirmed that the hydrogel can effectively prevent bleeding, sterilize and promote wound healing. Thus, this work highlights the great potential of the Cu_1.5Mn_1.5O₄/F127 hydrogel as a wound dressing for the treatment of bacterial infections and provides new research ideas for the application of nanozyme-based hydrogels in the medical field. STATEMENT OF SIGNIFICANCE: 1) Cu_1.5Mn_1.5O₄/F127 composite hydrogel exhibits enhanced multi-enzyme activity, ROS generation and GSH consumption, which improves the antibacterial therapeutic effect of traditional nanozymes. 2) Cu_1.5Mn_1.5O₄/F127 hydrogel has prominent photothermal properties and provides a multimodal synergistic antibacterial treatment platform. 3) Cu_1.5Mn_1.5O₄/F127 hydrogel can affect the core physiological activities of bacteria by blocking nucleotide metabolism and inhibiting protein expression, thereby achieving efficient sterilization. 4) The temperature sensitivity and hemostatic effect of Cu_1.5Mn_1.5O₄/F127 hydrogel enable it to promote wound healing while being effectively antibacterial. 5) Cu_1.5Mn_1.5O₄/F127 hydrogel can release Cu and Mn ions slowly in a weakly acidic environment on the wound surface, accelerating collagen deposition and angiogenesis and thereby promoting tissue repair.