Drug-resistant bacterial infections cause significant harm to public life, health, and property. Biofilm is characterized by overexpression of glutathione (GSH), hypoxia, and slight acidity, which is one of the main factors for the formation of bacterial resistance. Traditional antibiotic therapy gradually loses its efficacy against multi-drug-resistant (MDR) bacteria. Therefore, synergistic therapy, which regulates the biofilm microenvironment, is a promising strategy. A multifunctional nanoplatform, SnFe2O4-PBA/Ce6@ZIF-8 (SBC@ZIF-8), in which tin ferrite (SnFe2O4, denoted as SFO) as the core, loaded with 3-aminobenzeneboronic acid (PBA) and dihydroporphyrin e6 (Ce6), and finally coated with zeolite imidazole salt skeleton 8 (ZIF-8). The platform has a synergistic photothermal therapy (PTT)/photodynamic therapy (PDT) effect, which can effectively remove overexpressed GSH by glutathione peroxidase-like activity, reduce the antioxidant capacity of biofilm, and enhance PDT. The platform had excellent photothermal performance (photothermal conversion efficiency was 55.7 %) and photothermal stability. The inhibition rate of two MDR bacteria was more than 96 %, and the biofilm clearance rate was more than 90 % (150 μg/mL). In the animal model of MDR S. aureus infected wound, after 100 μL SBC@ZIF-8+NIR (150 μg/mL) treatment, the wound area of mice was reduced by 95 % and nearly healed. The serum biochemical indexes and H&E staining results were within the normal range, indicating that the platform could promote wound healing and had good biosafety. In this study, we designed and synthesized multifunctional nanoplatforms with good anti-drug-resistant bacteria effect and elucidated the molecular mechanism of its anti-drug-resistant bacteria. It lays a foundation for clinical application in treating wound infection and promoting wound healing.
Keywords: Biofilm; GSH depletion; Photodynamic therapy; Photothermal therapy; SnFe(2)O(4) nano-enzyme; Wound healing.
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