Forsythia suspensa-Derived Carbon Dot Nanozyme for Periodontitis Treatment via Antioxidative and Macrophage-Polarizing Activities.

Periodontitis is a chronic inflammatory disease driven by reactive oxygen species (ROS) overproduction and immune dysregulation. Carbon dots derived from traditional Chinese medicine (TCM) integrate the functional chemical features of herbal precursors with the favorable physicochemical properties of nanomaterials. As an exemplary case, we hydrothermally synthesized Forsythia suspensa-derived carbon dots (Fo-CDs), which exhibited a high superoxide dismutase (SOD)-like activity of 340 U/mg, along with catalase-mimicking and broad-spectrum free radical scavenging capacities. Mechanistically, Fo-CDs scavenged intracellular ROS in human periodontal ligament stem cells (hPDLSCs) and reprogrammed LPS-stimulated macrophages toward the anti-inflammatory M2 phenotype, as evidenced by downregulation of M1-related genes (iNOS, TNF-α, IL-6, IL-1β) and upregulation of M2-related genes (ARG1 and CD206). Therapeutically, in a rat periodontitis model, Fo-CDs attenuated alveolar bone loss, reduced inflammatory infiltration, reversed collagen disorganization, and suppressed osteoclast formation, indicating structural repair of periodontal tissues. Systemically, Fo-CDs restored redox balance by elevating SOD and GSH while lowering MDA and reduced serum levels of the proinflammatory cytokines TNF-α, IL-1β, and IL-6. Therefore, Fo-CDs effectively treat periodontitis by eliminating ROS and reprogramming macrophage polarization, showing their potential as a candidate therapeutic agent.