Macrophage-Targeted Glyconanoparticles Enhance Efferocytosis In Diabetic Periodontitis

This study developed a fluorescent-labeled glycopolymer (PTPEG) to deliver dimethyl itaconate (DI) to macrophages, enhancing efferocytosis and suppressing inflammation, offering a novel therapeutic strategy for diabetic periodontitis. Glyconanoparticles loaded with DI (PTPEG@DI) were prepared via solvent precipitation followed by dialysis. In vitro cellular experiments were performed to evaluate the anti-inflammatory, anti-oxidative, pro-efferocytosis, and osteogenic functions of PTPEG@DI by immunofluorescence staining, flow cytometry, apoptotic cell phagocytosis assay, and osteogenic induction. Apoptotic neutrophils were co-cultured with macrophages to evaluate efferocytosis efficiency.Eight-week-old male C57BL/6 mice (approved by the Ethics Committee) were used to establish diabetic periodontitis models which were divided into control, PTPEG, DI and PTPEG@DI treatment group. Drug distribution was analyzed by in vivo imaging. Micro-CT and tissue staining were used to evaluate alveolar bone regeneration. PTPEG@DI significantly reduced M1 marker (CD86) expression while promoting M2 marker (CD206), and reducing ROS generation. The efferocytosis efficiency of macrophages in the PTPEG@DI group was significantly higher than control group. Live imaging showed specific enrichment of PTPEG@DI in periodontal inflammation; micro-CT and tissue staining showed PTPEG@DI group significantly reduce periodontal tissue inflammation and alveolar bone destruction. PTPEG@DI synergistically enhance the efferocytosis, anti-inflammatory and bone regeneration functions by targeting macrophages to deliver DI. Targeting macrophages and synergistic effects offer an efficient treatment for diabetic periodontitis.