Artesunate carbon dots for attenuating periodontal inflammation and promoting bone regeneration via activation of AMPK

Periodontitis, recognized as a chronic inflammatory condition, manifests through sustained gingival inflammation and gradual degradation of alveolar bone tissue. Without proper intervention, this pathological process may culminate in permanent tooth detachment. Consequently, therapeutic strategies for periodontitis primarily focus on mitigating inflammatory reactions and stimulating osseous tissue regeneration. Recent pharmacological investigations have highlighted artesunate (ART) as a compound exhibiting notable anti-inflammatory efficacy, though its clinical application is constrained by limited aqueous solubility and suboptimal pharmacokinetic properties. Carbon-based quantum dots, emerging as versatile nanoscale materials, demonstrate multiple biological functionalities. This research successfully synthesized artesunate-derived carbon dots (ACDs) through hydrothermal synthesis and comprehensively evaluated their dual therapeutic effects on inflammation suppression and bone formation enhancement in periodontal disease models. Experimental data revealed that ACDs exhibit improved hydrophilicity, favorable biocompatibility, and simultaneous anti-inflammatory/osteogenic capabilities. Mechanistically, ACDs activated the adenosine monophosphate-activated protein kinase (AMPK), subsequently inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling transduction, which effectively reduced pro-inflammatory cytokine secretion. AMPK pathway activation further upregulated expression patterns of osteogenic differentiation markers at both mRNA translation and protein synthesis levels, enhanced mineralization capacity in rat bone marrow mesenchymal stem cells (rBMSCs), and increased calcified nodule formation. Collectively, these findings demonstrate that ACDs effectively counteract lipopolysaccharide (LPS)-induced inflammatory responses while substantially improving bone regenerative processes through AMPK pathway modulation. This investigation suggests ACDs as a promising nanotechnology-based approach for periodontitis management.