Janus Nanozyme With Programmable Catalytic Switching for Adaptive Therapy of Diabetic Wounds

ABSTRACT Diabetic wound healing requires dynamic bidirectional regulation of reactive oxygen species (ROS). Herein, guided by density functional theory (DFT) calculations, we propose a programmable strategy to engineer catalytic pathways via an intimate heterointerface in Janus‐structured Cu‐Ag nanoparticles (CuAg‐J). Theoretical simulations reveal that the unique Cu‐Ag heterointerface induces a charge transfer to oxygen intermediates, enabling spontaneous formation of reactive species and pH‑switchable catalytic activity. Under acidic conditions, CuAg‐J exhibits peroxidase (POD)‐like activity ( K m = 0.19 mM, V max = 0.38 µM/s) for antibacterial ROS generation. Under neutral conditions, it displays superoxide dismutase (SOD)‐like and catalase (CAT)‐like activities ( K m = 9.48 mM, V max = 6.88 µM/s) for ROS scavenging and oxygen production. In an infected diabetic wound model, this bidirectional ROS regulation effectively breaks the oxidative stress–hypoxia–inflammation vicious cycle, significantly accelerating healing and achieving 92.04% wound closure by Day 14. This study not only presents a high‐performance nanozyme but also provides a new design rationale for engineering intelligent catalytic materials capable of autonomous function switching in response to dynamic microenvironmental conditions.