NIR‐Triggered On‐Demand Synergistic Therapy for Multidrug‐Resistant Bacterial Infections Via a Smart Phase‐Transition Hydrogel

Abstract

The rise of multidrug‐resistant bacterial infections and biofilms poses a significant challenge to wound healing. Herein, we developed a temperature‐responsive gel–sol phase‐transition multifunctional hydrogel, named CPAM/GS, by incorporating a novel nanozyme, CeO2@PtAu@Mn2(CO)10, into a gelatin/sodium alginate matrix. The synthesized CeO2@PtAu@Mn2(CO)10 nanozyme exhibits multi‐enzyme activities, including peroxidase‐, oxidase‐, and catalase‐like properties, enabling it to generate ROS in response to the pH of the infected microenvironment and supply oxygen under hypoxic conditions. The CPAM/GS hydrogel demonstrates excellent photothermal performance (η = 47.99%) and allows on‐demand release of carbon monoxide (CO) and nanozymes upon NIR irradiation. In vitro experiments confirmed its potent antibacterial efficacy against methicillin‐resistant Staphylococcus aureus and Pseudomonas aeruginosa through the synergistic effects of photothermal therapy, chemodynamic therapy, and CO gas therapy, achieving a 100% and 99.8% antibacterial rate under NIR irradiation. Furthermore, this hydrogel effectively disrupts preformed biofilms, suppresses virulence gene expression, and promotes cell migration. In a mouse model of MRSA‐infected wounds, treatment with CPAM/GS hydrogel‐NIR(+) significantly accelerated wound healing, eliminated bacteria, and modulated wound microenvironment by reducing pro‐inflammatory cytokines and promoting angiogenesis. Its excellent biosafety and hemostatic performance were also confirmed. This work proposes a multifunctional synergistic strategy for treating multidrug‐resistant bacterial infections and promoting wound regeneration.