Zinc Oxide-Enhanced Copper Sulfide Nanozymes Promote the Healing of Infected Wounds by Activating Immune and Inflammatory Responses.

Bacterial infection and an excessive inflammatory response are two major factors that affect the healing of infected wounds. The zinc oxide/copper sulfide (ZnO-CuS) microspheres (MSs) developed in this work can kill bacteria and resist inflammation. ZnO-CuS exhibits different enzyme-like activities depending on pH. In acidic environments, ZnO-CuS exhibits peroxidase-like (POD-like) activity and can convert hydrogen peroxide (H2O2) into hydroxyl radicals (•OH) for sterilization. Under neutral conditions, ZnO-CuS removes reactive oxygen species (ROS) and can convert excess ROS into water and oxygen. The in vitro results of the antibacterial test demonstrate the pronounced disruption effect of ZnO-CuS on the bacterial biofilm and cell membrane. The transcriptome sequencing results of wounded animal tissue reveal that ZnO-CuS MSs increase the expression of proteins produced by immune cells, and reduce the expression levels of inflammatory factors at the wound site. Therefore, antimicrobial activity and rapid wound healing can be achieved by regulating the immune response and reducing the inflammatory response. The results from hemolysis, routine blood and blood biochemistry analyses demonstrate the excellent biosecurity of the ZnO-CuS MSs.