A microenvironment-responsive hydrogel is developed incorporating polymyxin B-modified AuMnCu nanozymes and dual drugs (tannic acid and tobramycin). At infection sites, it generates ROS, releases drugs responsively, and enhances mild photothermal action to disrupt bacterial redox balance. After disinfection, it self-switches to scavenge ROS, reduce hypoxia, and stimulate angiogenesis, enabling precise and programmed repair of infected wounds.
Abstract
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.
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