Pt-Induced Sublattice Distortion Facilitates Enzyme Cascade Reactions for Eradicating Intracellularly Methicillin-Resistant Staphylococcus aureus and Enhancing Diabetic Wound Healing

Abstract

Metal oxide nanozymes hold significant potential in combating bacterial infections; however, their ordered crystal structures limit the enhancement of catalytic activity, posing challenges in addressing clinical needs for eliminating intracellularly colonized bacteria. Here, we report the development of an integrated diagnostic-therapeutic microneedle patch incorporates the Res@PtZ-Z nanozyme hybrid. Res@PtZ-Z consists of a ZIF shell loaded with the natural compound resveratrol (Res), encapsulating a Pt-doped zinc oxide (ZnO) nanozyme core (PtZ). The Res component modulates charge distribution on the ZIF shell and attenuates bacterial virulence, thereby promoting the uptake of Res@PtZ-Z by host cells. The PtZ core, doped with Pt⁴⁺ to induce sublattice distortion in ZnO, exhibits oxidase-like, peroxidase-like, and catalase-like activities. Under intracellular hypoxic conditions, the cascade of these enzyme-like activities ensures a sustained generation of reactive oxygen species (ROS), enabling robust antibacterial effects. Additionally, Res@PtZ-Z enables real-time infection monitoring by oxidizing the 3,3′,5,5′-tetramethylbenzidine (TMB) substrate to produce a distinct colorimetric response. This approach addresses both methicillin-resistant Staphylococcus aureus (MRSA) invasion and intracellular persistence, contributing to improved infection management and promoting wound healing.