Melatonin-Derived Carbon Dots with Free Radical Scavenging Property for Effective Periodontitis Treatment via the Nrf2/HO-1 Pathway

Periodontitis is a chronic inflammatory disease closely associated with reactive oxygen species (ROS) involvement. Eliminating ROS to control the periodontal microenvironment and alleviate the inflammatory response could potentially serve as an efficacious therapy for periodontitis. Melatonin (MT), renowned for its potent antioxidant and anti-inflammatory characteristics, is frequently employed as an ROS scavenger in inflammatory diseases. However, the therapeutic efficacy of MT remains unsatisfactory due to the low water solubility and poor bioavailability. Carbon dots have emerged as a promising and innovative nanomaterial with facile synthesis, environmental friendliness, and low cost. In this study, melatonin-derived carbon dots (MT-CDs) were successfully synthesized via the hydrothermal method. The MT-CDs have good water solubility and biocompatibility and feature excellent ROS-scavenging capacity without additional modification. The in vitro experiments proved that MT-CDs efficiently regulated intracellular ROS, which maintained mitochondrial homeostasis and suppressed the production of inflammatory mediators. Furthermore, findings from the mouse model of periodontitis indicated that MT-CDs significantly inhibited the deterioration of alveolar bone and reduced osteoclast activation and inflammation, thereby contributing to the regeneration of damaged tissue. In terms of the mechanism, MT-CDs may scavenge ROS, thereby preventing cellular damage and the production of inflammatory factors by regulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. The findings will offer a vital understanding of the advancement of secure and effective ROS-scavenging platforms for more biomedical applications.