Biofilm Microenvironment-Mediated MoS₂ Nanoplatform with Its Photothermal/Photodynamic Synergistic Antibacterial Molecular Mechanism and Wound Healing Study.

Drug-resistant bacterial infections pose a serious threat to human public health. Biofilm formation is one of the main factors contributing to the development of bacterial resistance, characterized by a hypoxic and microacidic microenvironment. Traditional antibiotic treatments have been ineffective against multidrug-resistant (MDR) bacteria. Novel monotherapies have had little success. On the basis of the photothermal effect, molybdenum disulfide (MoS₂) nanoparticles were used to link quaternized polyethylenimine (QPEI), dihydroporphyrin e6 (Ce6), and <i>Panax notoginseng</i> saponins (PNS) in a zeolitic imidazolate framework-8 (ZIF-8). A multifunctional nanoplatform (MQCP@ZIF-8) was constructed with dual response to pH and near-infrared light (NIR), which resulted in synergistic photothermal and photodynamic antibacterial effects. The nanoplatform exhibited a photothermal conversion efficiency of 56%. It inhibited MDR <i>Escherichia coli</i> (<i>E. coli</i>) and MDR <i>Staphylococcus aureus</i> (<i>S. aureus</i>) by more than 95% and effectively promoted wound healing in mice infected with MDR <i>S. aureus</i>. The nanoplatform induced the death of MDR bacteria by promoting biofilm ablation, disrupting bacterial cell membranes and intracellular DNA, and interfering with intracellular material and energy metabolism. In this study, a multifunctional nanoplatform with good antibacterial effect was developed. The molecular mechanisms of MDR bacteria were also elucidated for possible clinical application.