Trimetallic Nanozyme‐Embedded Smart Hydrogel Enables NIR‐Controlled Bacterial Killing and Oxidative Stress Alleviation

Nanozyme-based antibacterial therapy is limited by inefficient single-component nanozymes and complex infection microenvironments. A mild near infrared-I (NIR-I) photothermal-enhanced nanozyme catalytic system is developed using polymyxin B-modified trimetallic nanoparticles (AuMnCu) embedded in a smart hydrogel (AMCB-FTB) formed by 3-formylphenylboronic acid (FPBA), tobramycin (TOB), and tannic acid (TA). The AuMnCu nanozymes exhibit self-switching multi-enzyme activity, generating ROS for bacterial killing in non-NIR mode while scavenging ROS and producing oxygen post-disinfection to alleviate oxidative stress and hypoxia, promoting wound healing. Under NIR-I irradiation, mild hyperthermia (≈44.3 °C) further boosts catalytic activity, enhancing sterilization. The AMCB-FTB hydrogel is injectable, pH-/temperature-responsive, and releases tobramycin/tannic acid in acidic infection microenvironments, synergizing with photothermal therapy (PTT) and nanozyme activity for potent antibacterial effects. In vitro and in vivo studies confirm AMCB-FTB's programmable antibacterial, anti-inflammatory, and pro-regenerative functions via microenvironment self-regulation. RNA sequencing analysis confirm that AMCB-FTB combined with NIR disrupts bacterial energy metabolism, protein synthesis, and lipid pathways, effectively suppressing survival, motility, biofilm formation, and virulence. This work reports a microenvironment-responsive hydrogel with enzyme-mimetic ROS modulation properties, providing a novel pathway to develop thermal-enhanced catalytic materials for refractory diabetic wounds and infectious diseases.