Nitrogen and Sulfur Codoped Carbon Dots Synergize Tyrosinase Inhibition, ROS Scavenging, and UVB Shielding to Rebalance Photodamage and Pigmentation

Conventional depigmenting agents suppress tyrosinase to reduce melanin but can compromise endogenous photoprotection, resulting in a persistent trade-off between whitening efficacy and UV resilience. Here, we engineer sulfur codoped carbon dots derived from arbutin and niacinamide (N, S-ANCD) to integrate enzymatic inhibition, ROS management, and UVB attenuation within a single ultrasmall nanoplatform. Spectroscopic characterization confirms sulfur incorporation and defect-enriched surface states that broaden UV absorption and favor nonradiative energy dissipation. N, S-ANCD exhibits strengthened tyrosinase inhibition and enhanced DPPH/ABTS radical quenching in vitro while maintaining low cytotoxicity and good hemocompatibility. In zebrafish, N, S-ANCD reduces melanin deposition within a defined safety window and mitigates UVB-induced tail-fin injury in both prevention and posttreatment paradigms. Mechanistically, N, S-ANCD lowers ROS accumulation and lipid peroxidation, restores antioxidant enzyme activities, and reduces injury-associated fluorescence signals consistent with attenuated cell stress. Transcriptomic profiling further indicates coordinated reversal of UV-activated inflammatory and ferroptosis-related programs and normalization of extracellular matrix/adhesion remodeling toward tissue homeostasis. Together, these results demonstrate that sulfur codoped carbon dots enable low-dose depigmentation while maintaining photoprotection, and highlight defect- and surface-state modulation as a viable design principle for multifunctional cosmetic nanomaterials.