Engineering Pt-decorated g-C3N4 nanosheets with Fe3+ and chitosan for amplified photodynamic ROS production and hydrogen-mediated ATP depletion.

Graphitic carbon nitride (g-C3N4) has attracted considerable attention as a multifunctional platform for cancer therapy, including photodynamic therapy (PDT) and hydrogen (H2)-based therapeutic strategies, owing to its intrinsic photocatalytic activity. Nevertheless, its clinical translation is hindered by rapid photogenerated electron-hole recombination and tumor-associated defense mechanisms, such as elevated glutathione (GSH) levels and hypoxic microenvironments. In this work, we report the development of chitosan-modified g-C₃N₄ nanosheets (OCN/Pt-CTS) as a synergistic anticancer nanoplatform. Surface functionalization with chitosan significantly enhances the biocompatibility, aqueous dispersibility, and structural stability of the nanosheets. The incorporation of platinum (Pt) nanoparticles with multiple oxidation states effectively improves charge separation, facilitates reactive oxygen species (ROS) generation, promotes H2 and O2 evolution, and induces intracellular GSH depletion. Furthermore, the coordination of Fe3+ ions activates a photo-Fenton reaction, thereby amplifying ROS production and enhancing cancer cell cytotoxicity. Comprehensive structural and functional characterizations, including FT-IR, 1H NMR, TGA, XPS, HRTEM, and electrochemical analyses, confirmed the successful construction of the nanocomposite and its superior charge-carrier dynamics. Under visible-light irradiation, OCN/Pt-CTS exhibited markedly enhanced cytotoxicity toward A375 melanoma cells, with an IC₅₀ value of 33 μg/mL, compared to a substantially higher IC₅₀ of 290 μg/mL under dark conditions.