Melanoma, a highly aggressive cutaneous tumor, demands the development of highly biocompatible and efficient photothermal nanomaterials to advance photothermal therapy. In this study, we synthesized saffron-derived carbon dots (S-CDs) via a solvothermal method using saffron, a traditional Chinese medicine, as the carbon source. Characterization by high-resolution transmission electron microscopy showed that the S-CDs are well-monodispersed with an average size of about 2.4 nm and exhibit a photothermal conversion efficiency of 31.9%. Under 808 nm laser irradiation, S-CDs demonstrated both concentration-dependent temperature increase and reactive oxygen species (ROS) generation. The critical role of ROS in the cytotoxic mechanism was confirmed by scavenger assays. To enhance tumor retention, we developed an injectable hydrogel (S-CDs@HA) by encapsulating S-CDs into an aldehyde-modified hyaluronic acid matrix. The hydrogel exhibited sustained release kinetics, enabling sustained release over 144 h. In a B16F10 melanoma mouse model, local administration of S-CDs@HA combined with laser irradiation significantly suppressed tumor growth, as evidenced by histopathological analysis revealing extensive necrosis and decreased proliferation. No systemic toxicity was observed based on body weight monitoring and organ histology. This work thus presents not only a novel natural product-derived photothermal agent but also delivers an injectable hydrogel platform for the synergistic photothermal and ROS-mediated therapy of melanoma.
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