A mesoporous iron single-atom nanozyme with cascade ROS scavenging and antibiotic/antimicrobial peptide co-delivery...

Bacterial infected inflammation is a major cause of delayed wound healing, and single antibacterial or anti-inflammatory strategies are often insufficient to address the complex infectious microenvironment. To overcome this limitation, we employed a dual-template strategy to construct a hollow-structured Fe single-atom nanozyme (Fe-mNC) with a hierarchical micro/mesoporous structure and further developed a nanozyme-based drug delivery system (FNMA) to achieve synergistic antibacterial and anti-inflammatory therapy. The introduction of mesoporous architecture significantly increased the specific surface area and mass-transfer efficiency while maintaining highly dispersed Fe-N₄ single-atom active sites, endowing Fe-mNC with excellent superoxide dismutase- and catalase-like cascade catalytic activities for efficient reactive oxygen species (ROS) scavenging. Benefiting from its structural advantages, Fe-mNC enabled efficient loading and release of the antibiotic moxifloxacin (MOX) and antimicrobial peptides (AMPs), resulting in synergistic antibacterial effects. In vitro studies demonstrated that the disruption of bacterial membranes by AMPs significantly enhanced the accessibility of MOX, leading to improved bactericidal efficacy, while Fe-mNC effectively eliminated excess ROS and alleviated cellular oxidative stress. Furthermore, a S.aureus-infected mouse skin wound model confirmed that FNMA significantly eliminated bacteria at the infection site, suppressed inflammatory responses, promoted collagen deposition and angiogenesis, and accelerated wound closure, while exhibiting favorable biocompatibility and in vivo safety. Overall, this work presents a multifunctional therapeutic strategy that integrates mesoporous single-atom nanozyme catalysis with synergistic antibacterial drug delivery, offering a promising materials design and potential solution for the effective treatment of bacterial infected wounds.