Copper Silicate Nanoparticles and β-Lapachone-Based Postoperative Recurrence Suppression of Cutaneous Melanoma

The postoperative management of melanoma is significantly threatened by high risks of tumor recurrence and impaired wound healing. Selectively eliminating residual tumor cells while preserving the biocompatibility to normal skin cells remains a major research challenge. Chemodynamic therapy (CDT) has been widely reported to selectively eradicate tumor cells, and thus demonstrates potential to address this challenge. However, the efficacy of CDT is often limited by inadequate intracellular levels of hydrogen peroxide (H 2 O 2 ) and the overexpression of glutathione (GSH). To overcome these limitations, we developed a combinatorial strategy using copper silicate nanoparticles (CSO NPs) and β-lapachone (β-Lap). This strategy enables reactive oxygen species (ROS) cascade amplification within tumor cells: β-Lap promotes H 2 O 2 generation via NADPH: quinone oxidoreductase 1 (NQO1); the resulting H 2 O 2 reacts with Cu 2+ from CSO NPs through a Fenton-like reaction, producing highly toxic •OH; simultaneously, Cu 2+ depletes GSH, reducing ROS scavenging. This cascade significantly enhances CDT efficacy. In normal cells, low NQO1 expression prevents this ROS amplification, ensuring biocompatibility. Furthermore, SiO 4 4– released from CSO NPs promote collagen deposition and angiogenesis, accelerating wound healing. Accordingly, we engineered a sprayable, in situ-forming hydrogel (CSO/β-Lap@PF127) by dispersing CSO NPs and β-Lap in thermosensitive Pluronic F127. In murine models of postoperative melanoma and full-thickness skin defects, the hydrogel effectively suppressed tumor recurrence and promoted wound healing. Therefore, CSO/β-Lap@PF127 demonstrates considerable potential for postoperative melanoma management.