Single-atom silver decorated MoS2-PEG nanoparticles as a novel antibacterial and immunomodulatory therapy for periodontitis: a catalysis-inspired nanotherapeutic strategy

Antibacterial and immunomodulatory strategies play crucial roles in the management of periodontitis. Inspired by single-atom catalysis, we developed a nanotherapeutic platform by anchoring atomically dispersed Ag onto polyethylene glycol-functionalized molybdenum disulfide (MoS 2 -PEG) and evaluated its therapeutic potential for periodontitis. A solvothermal strategy was employed to synthesize MoS 2 , followed by surface functionalization with polyethylene glycol and precise anchoring of single Ag atoms, ultimately yielding Ag-MoS 2 -PEG. The in vitro antibacterial efficacy of the nanomaterials was evaluated using colony-forming unit (CFU) assays, live/dead bacterial staining, and scanning electron microscopy (SEM). In vivo antibacterial activity was assessed by Giemsa staining of periodontal tissues infected with periodontal pathogens. Macrophage polarization was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence, and flow cytometry. Reactive oxygen species (ROS) and glutathione (GSH) levels were measured using 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) and Ellman’s reagent, respectively. A ligature-induced rat model of periodontitis was used to evaluate the therapeutic efficacy of the nanomaterials. Upon exposure to 660 nm irradiation, Ag-MoS 2 -PEG effectively eradicated periodontal pathogens through mechanisms including physical disruption, ROS generation, and interference with glutathione homeostasis. In vitro studies revealed that Ag-MoS 2 -PEG facilitated the polarization of macrophages towards the anti-inflammatory M2 phenotype, thereby reducing the M1/M2 ratio. In vivo experiments indicated that Ag-MoS 2 -PEG inhibited the expression of inducible nitric oxide synthase (iNOS), decreased the number of osteoclasts, and alleviated alveolar bone resorption. Biosafety assessments confirmed the compound’s favorable biocompatibility and minimal cytotoxicity at therapeutic concentrations. The findings underscore the potential of Ag-MoS₂-PEG as a multifaceted and efficacious therapeutic agent in periodontology, offering a novel strategy for combating periodontal pathogens and modulating the immune response.