Constructing multifunctional Cu Single-Atom nanozyme for synergistic nanocatalytic Therapy-Mediated...

Developing an effective strategy to combat multi-drug-resistant (MDR) bacteria and promote wound healing without overuse of antibiotics remains an important and challenging goal. Herein, we established a synergistic reactive oxygen species (ROS) and reactive nitrogen species (RNS)-mediated nanocatalytic therapy, which was consisted of a multifunctional Cu single-atom nanozyme loaded with the l-arginine (l-Arg@Cu-SAzymes) and a low level of hydrogen peroxide (H₂O₂) as a trigger. l-Arg@Cu-SAzymes can possess excellent dual enzyme-like activities: catalase (CAT)-like activity that decompose H₂O₂ into O₂, and subsequent oxidase (OXD)-like activity that convert O₂ to cytotoxic superoxide anion radical (•O₂^-). Meanwhile, l-Arg@Cu-SAzymes can also be triggered by H₂O₂ to release nitric oxide (NO), which can continue to react with •O₂^- to generate more lethal peroxynitrite (ONOO^-). Collectively, the synergistic ROS and RNS mediated by l-Arg@Cu-SAzymes endow the treatment system with an outstanding antibacterial ability against MDR bacteria and reduce the inflammation at the wound site. Furthermore, l-Arg@Cu-SAzymes-mediated NO and O₂ release promote the cell proliferation, collagen synthesis, and the angiogenesis, as well as facilitate macrophage polarization to reparative M2 phenotype, thereby accelerating wound closure and tissue remodeling. Therefore, l-Arg@Cu-SAzymes-based synergistic nanocatalytic therapy can be regarded as a promising strategy for MDR bacterial infected wounds treatment, owing to their potent antibacterial efficacy and enhanced tissue remodeling effects.