GSH-Triggered Nitric Oxide Release from Polyurethane Nanocarriers for Gas-Photothermal Synergistic Therapy of Bacterial-Infected Wounds

Wound bacterial infections pose a significant challenge to global public health. Nitric oxide (NO), an endogenous gaseous molecule, shows great potential in antibacterial therapy. However, efficient NO delivery remains a critical challenge. Photothermal therapy (PTT) offers a noninvasive and highly localized treatment for bacterial infections. Leveraging the advantages of both approaches, this study developed a polymer-based nanocarrier to achieve synergistic NO delivery and PTT. For the first time, an amphiphilic polyurethane PEG-PNU-PEG containing dinitrate NO donors were synthesized, which further self-assembled into polymeric nanomicelles loaded with a NIR emitting conjugated polymer. In the bacterial microenvironment, elevated glutathione (GSH) triggered NO release. Simultaneously, the conjugated polymer enabled effective photothermal therapy, further promoting NO release for gas therapy. Experimental results demonstrated that the synergistic NO and PTT treatment effectively eradicated bacteria, eliminating 69.93% ± 2.79% of <i>S. aureus</i> biofilm, a > 4.5-fold improvement compared to NO treatment alone (14.8% ± 2.92%). The <i>in vitro</i> antibacterial assay showed an inhibition rate exceeding 99.0%, while <i>in vivo</i> studies on infected skin wounds revealed a bacterial clearance rate of 95.0% ± 1.95%. Furthermore, this system suppressed inflammatory cytokines, promoted collagen deposition, and accelerated skin regeneration, providing an effective strategy for broad-spectrum antibacterial therapy and wound healing.