Single-atom nanozymes with intelligent response to pathological microenvironments for bacterially infected wound healing

Abstract

Wound healing is a complex and dynamic process often accompanied by bacterial infection, inflammation, and excessive oxidative stress. Single-atom nanozymes with multi-enzymatic activities show significant potential for promoting the healing of infected wounds by modulating their antibacterial and anti-inflammatory properties in response to the wound's physiological environment. In this study, we synthesized MN₄ single-atom nanozymes with multi-enzymatic activities that intelligently respond to pH value changes in the wound healing process. In vitro experiments confirm their effectiveness against Gram-negative bacteria, attributed to elevated reactive oxygen species (ROS) accumulation within the bacterial cells. Moreover, a full-thickness skin wound-infected model demonstrates that MN₄ single-atom nanozymes accelerate wound repair and skin regeneration by suppressing the expression of tumor necrosis factor-alpha (TNF-α), promoting angiogenesis, and enhancing collagen deposition. In vivo biocompatibility experiments further demonstrate the favorable biocompatibility of these nanozymes, highlighting their potential for clinical applications in infected wound healing. These nanozymes respond intelligently to different microenvironments and may be suitable for addressing further complex and variable diseases.