Constructing multifunctional Cu Single-Atom nanozyme for synergistic nanocatalytic Therapy-Mediated Multidrug-Resistant bacteria infected wound healing

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 (H 2 O 2 ) as a trigger. l -Arg@Cu-SAzymes can possess excellent dual enzyme-like activities: catalase (CAT)-like activity that decompose H 2 O 2 into O 2 , and subsequent oxidase (OXD)-like activity that convert O 2 to cytotoxic superoxide anion radical (•O 2 − ). Meanwhile, l -Arg@Cu-SAzymes can also be triggered by H 2 O 2 to release nitric oxide (NO), which can continue to react with •O 2 – 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 O 2 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.