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 <i>Porphyromonas gingivalis</i> while simultaneously suppressed the inflammatory response of macrophages induced by lipopolysaccharide from <i>Porphyromonas gingivalis</i>. 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.