ROS-Responsive Hydrogel-Encapsulated MoS2 Nanospheres for Photothermal Antibacterial and Wound Healing Promotion Therapy

The overuse of antibiotics leads to bacterial resistance, which involves complex and diverse mechanisms, among which the activation of drug efflux pumps is a key contributing factor. Excessive accumulation of reactive oxygen species (ROS) in inflamed wound tissues further exacerbates this issue by triggering efflux pump activation. To address bacterial resistance, this study aimed to mitigate ROS accumulation, thereby inhibiting efflux pump expression and enhancing antibacterial efficacy. Researchers synthesized MoS2-based nanocomposites (MoS2/ZnO/Cur designated as MZCs) loaded with ZnO and Cur into cross-linked structures using a hydrothermal method and combined them with photothermal therapy (PTT). To enhance functionality, a ROS-responsive hydrogel was developed by conjugating CGG with a ROS-responsive linker (TPA) and integrating the MZCs, yielding MZC@CGG-TPA. Electron microscopy revealed the internal structure of the hydrogel. Antibacterial assays demonstrated that MZC@CGG-TPA achieved inhibition rates exceeding 95% against multidrug-resistant (MDR) Escherichia coli and Staphylococcus aureus, with biofilm clearance rates surpassing 90%. Photothermal performance testing indicated a photothermal conversion efficiency of 47%. Transcriptomic analysis revealed that MZC@CGG-TPA suppressed the expression of channel protein-related genes, downregulated the key regulator gene marA, and inhibited drug efflux pump activity. This enhanced the retention of antibacterial agents within bacterial cells and improved bactericidal efficacy. Under laser irradiation, the MZC@CGG-TPA hydrogel dressing significantly enhanced anti-infection efficacy and accelerated wound healing in an in vivo wound infection model. These findings present an approach for designing advanced nanosystems to effectively combat MDR bacteria.