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.