Fluorinated polyamidoamine-mediated delivery of miRNA-23b to alleviate inflammation and bone loss in periodontitis.

Periodontitis is a chronic inflammatory disease characterized by the destruction of periodontal tissues, and is driven by dysregulated immune responses and persistent inflammation. Despite traditional treatments, effective therapeutic strategies targeting the underlying mechanism are still limited. Emerging evidence suggests that miR-23b plays a regulatory role in controlling the inflammation, but its function and therapeutic potential in periodontitis remain unexplored. In this study, the miR-23b level was identified to be significantly downregulated in gingival tissues from both clinical periodontitis patients and a rat periodontitis model. To restore its function, fluorinated polyamidoamine (FP) was employed as the carrier to achieve the miR-23b delivery into inflammatory macrophages. The FP/miR-23b nanoparticles effectively suppressed the NF-κB activation by targeting TAB2, TAB3 and IKK-α, leading to the reduced levels of pro-inflammatory cytokines. In the rat periodontitis model, FP/miR-23b nanoparticles were effectively delivered to periodontal macrophages, resulting in reduced local inflammation and inflammatory cell infiltration, and alleviated alveolar bone resorption. Meanwhile, no adverse effects on body weight or major organs were observed, suggesting the favorable biocompatibility of FP/miR-23b nanoparticles. These findings suggested that FP-mediated miR-23b delivery represented a potential therapeutic approach for periodontitis through host inflammatory modulation and alveolar bone protection.