Pre-chelated gallium-loaded polydopamine nanoparticles as a multifunctional regulator of osteoblast/osteoclastogenesis for the synergistic therapy of periodontitis

Periodontitis, a chronic inflammatory disease caused by local microbial dysbiosis and host immune imbalance, is prevalent on a global scale. Its progression is associated with an imbalance of pro- and anti-inflammatory cytokines, as well as osteoclast-mediated alveolar bone resorption. However, conventional non-surgical treatments exhibit limited efficacy due to the complex topography of periodontal pockets, instrumental limitations, antibiotic resistance, and the reliance on single-treatment strategies. This underscores the necessity for innovative therapeutic approaches. In this study, based on comprehensive treatment strategy of periodontitis, we designed and synthesized the pH-responsive PDA-Ga3+ nanoparticles (PDA-Ga3+ NPs) via a pre-chelated method. In vitro, PDA-Ga3+ NPs significantly inhibited the growth and biofilm formation of Porphyromonas gingivalis while simultaneously suppressed the inflammatory response of macrophages induced by lipopolysaccharide from Porphyromonas gingivalis. Furthermore, the improvement in osteoblastogenesis by PDA-Ga3+ NPs, as well as activation of Akt1-mTOR pathway reduced autophagy in preosteoclast and suppressed osteoclast formation, achieving dual regulation of bone remodeling. In vivo, PDA-Ga3+ NPs inhibited autophagy in alveolar bone resorption, alleviated periodontitis progression, and reduced inflammatory cytokine expression in gingival tissues. PDA-Ga3+ NPs offered a synergistic approach to antimicrobial, anti-inflammatory, and bone homeostasis regulation, holding innovative strategy for non-surgical treatment of periodontitis and potential clinical application value.