NIR-responsive Cu2-xSe@Fc Nanoparticles for Photothermal- Ferroptosis Combination Therapy in Esophageal Cancer

Photothermal therapy (PTT), combined with ferroptosis, has attracted considerable attentions, emerging as a promising novel strategy for EC treatment. Therefore, there is a critical need to develop a drug delivery system capable of effectively integrating these two therapeutic approaches. In the present study, we report a novel drug delivery system based on ferrocene (Fc), which is mixed with lauric acid and then coated on the surface of Cu2-xSe nanoparticles (NPs). The photothermal properties of Cu2-xSe triggers the melting of lauric acid under near-infrared (NIR) laser irradiation, facilitating controlled release of Fc. Following internalization by tumor cells via endocytosis, the synergistic effect of PTT and ferroptosis, triggered by Cu2-xSe@Fc, led to immunogenic cell death (ICD), which promoted the maturation of dendritic cells (DCs) and the recruitment of cytotoxic T lymphocytes (CTLs), resulting from the strengthened antitumor immune surveillance.