Treatment Of Periodontitis With Polyphenol/Minocycline Self-Assembled Nanosystem

1. To explore the effects of EGCG-minocycline nanosystem (EM-NPs) on pyroptosis inhibition and inflammation regulation. 2. To clarify the antibacterial ability and underlying mechanisms of EM-NPs against periodontal pathogens. In this study, a modular self-assembly strategy for EM NPs is developed through hierarchical molecular design, leveraging non-covalent interactions between polyphenols and antibiotic molecules. Various material characterization techniques were employed to examine the morphology, particle size, chemical composition, and other physicochemical properties of the material. Cytocompatibility and cellular uptake behavior of the material were assessed using CCK-8 assays, Live/Dead assays, and confocal laser scanning microscopy. Subsequently, the pyroptosis inhibition effects and mechanisms of EM NPs were evaluated using qRT-PCR, immunofluorescence staining, flow cytometry, ELISA, and Western blot. The antibacterial activity of EM-NPs against pathogenic bacteria and biofilms was evaluated through plate counting, scanning electron microscopy, and live/dead staining assays, among other tests. Finally, a mouse periodontitis model was established to validate the therapeutic efficacy of EM-NPs. 1. EM NPs enhance antibacterial activity by leveraging polyphenol affinity for bacterial outer membrane proteins, and outperform the free antibiotic in biofilm clearance and intracellular bactericidal efficacy. 2. EM NPs protect macrophages from pyroptosis by eliminating mitochondrial ROS (mtROS), maintaining mitochondrial homeostasis, reducing intracellular free mitochondrial DNA (mtDNA) levels, and suppressing inflammasome activation, thereby alleviating inflammation. The successfully constructed EM-NPs exhibited multifaceted effects, including antibacterial activity, pyroptosis inhibition, and inflammation control, demonstrating significant potential for therapeutic applications.