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A mild near infrared\u2010I (NIR\u2010I) photothermal\u2010enhanced nanozyme catalytic system is developed using polymyxin B\u2010modified trimetallic nanoparticles (AuMnCu) embedded in a smart hydrogel (AMCB\u2010FTB) formed by 3\u2010formylphenylboronic acid (FPBA), tobramycin (TOB), and tannic acid (TA). The AuMnCu nanozymes exhibit self\u2010switching multi\u2010enzyme activity, generating ROS for bacterial killing in non\u2010NIR mode while scavenging ROS and producing oxygen post\u2010disinfection to alleviate oxidative stress and hypoxia, promoting wound healing. Under NIR\u2010I irradiation, mild hyperthermia (\u224844.3\u00a0\u00b0C) further boosts catalytic activity, enhancing sterilization. The AMCB\u2010FTB hydrogel is injectable, pH\u2010\/temperature\u2010responsive, 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\u2010FTB's programmable antibacterial, anti\u2010inflammatory, and pro\u2010regenerative functions via microenvironment self\u2010regulation. RNA sequencing analysis confirm that AMCB\u2010FTB 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\u2010responsive hydrogel with enzyme\u2010mimetic ROS modulation properties, providing a novel pathway to develop thermal\u2010enhanced catalytic materials for refractory diabetic wounds and infectious diseases.<\/jats:p>","DOI":"10.1002\/advs.202512875","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T13:17:02Z","timestamp":1759497422000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Trimetallic Nanozyme\u2010Embedded Smart Hydrogel Enables NIR\u2010Controlled Bacterial Killing and Oxidative Stress Alleviation"],"prefix":"10.1002","volume":"12","author":[{"given":"Zehui","family":"Xiao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Food Nutrition and Safety College of Food Science and Engineering Tianjin University of Science and Technology  Tianjin 300457 P. R. 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