Self‑oxygenating nanoparticle-mediated photodynamic therapy for biofilm control and macrophage immunomodulation in...

Periodontitis is a chronic biofilm-induced inflammatory disease that is increasingly linked to systemic conditions. Effective treatment requires removing pathogenic biofilms and modulating the host inflammatory response. Antibacterial photodynamic therapy (aPDT) shows promising potential in the field of antibacterial treatment. However, issues such as the hypoxic microenvironment within periodontal pockets and biofilm structures, as well as the poor stability of traditional photosensitizers, pose challenges to the efficacy of aPDT. Here, we developed a multifunctional nanoparticle MB-MnO₂@PLGA NPs (MMP NPs) by co-encapsulating methylene blue (MB) and PVA-pre-dispersed manganese dioxide (MnO₂) nanosheets into a PLGA nanocarrier using a double emulsion-solvent evaporation method. Characterization confirmed their core-shell morphology, good colloidal stability, and high MB loading. Upon 660 nm irradiation, the nanoparticles generated reactive oxygen species and catalyzed H₂O₂ to produce oxygen, relieving local hypoxia and enhancing the cell compatibility of free MB. The MMP NPs disrupted P. gingivalis and F. nucleatum biofilms and exhibited superior antibacterial activity compared to free MB. Additionally, the nanoplatform significantly downregulated IL-6 and TNF-α levels. Importantly, the nanoplatform promoted macrophage polarization toward an anti-inflammatory M2 phenotype, as indicated by increased Arg-1 and CD206 expression. This work supports a synergistic in vitro strategy that simultaneously targets infection, hypoxia, and inflammation. It holds positive significance for promoting the development of periodontal disease treatment.