Iron Single-Atom\nNanozyme with Inflammation-Suppressing\nfor Inhibiting Multidrug-Resistant Bacterial Infection and Facilitating\nWound Healing

Infection with drug-resistant bacteria and the formation\nof biofilms\nare the main factors contributing to wound healing insufficiency.\nAntibacterial agents with enzyme-like properties have exhibited considerable\npotential for efficient eradication of drug-resistant microorganisms\ndue to their superior sensitivities and minimal side effects. In this\nwork, we prepared a kind of Fe-centered single-atom nanozyme (Fe-SAzyme)\nwith high biocompatibility and stability via a facile one-pot hydrothermal\nmethod, which was suitable for the treatment of wounds infected with\ndrug-resistant bacteria. The Fe-SAzyme exhibited remarkable peroxidase-like\ncatalytic activities, catalyzing the conversion of hydrogen peroxide\n(H<sub>2</sub>O<sub>2</sub>) to highly toxic hydroxyl radicals (<sup>•</sup>OH), which could not only damage bacterial cells but\nalso inhibit, disrupt, and eradicate the formation of bacterial biofilms.\nThus, Fe-SAzyme demonstrated a broad-spectrum antibacterial performance\ncapable of effectively eliminating multidrug-resistant bacteria. The\ncoexistence of ferrous (Fe<sup>2+</sup>) and ferric (Fe<sup>3+</sup>) ions in Fe-SAzyme conferred the nanozyme with anti-inflammatory\nactivity, effectively suppressing excessive inflammation. Meanwhile,\nFe-SAzyme could significantly downregulate inflammatory cytokines\ntumor necrosis factor-α and interleukin-1β and upregulate\ngrowth factors VEGF and epidermal growth factor, which can prevent\nbacterial infection, mitigate inflammation, promote fibroblast proliferation,\nand improve wound closure. Thus, Fe-SAzyme had shown favorable therapeutic\nefficiency in promoting bacteria-infected wound healing. This study\nprovides Fe-SAzyme as a promising candidate for the development of\nnew strategies to treat multidrug-resistant bacterial infections.