Biodegradable Bismuth Nanostructures as a Ferroptosis Inducer for Phototherapy of Breast Cancer

The therapeutic efficacy of monotherapy on tumors is often limited due to the constraints of tumor response conditions, significantly impacting clinical treatment outcomes. In this study, we design a collaborative therapeutic nanosystem (BBSP) that combines photodynamic therapy (PDT) and photothermal therapy (PTT). The system is formulated by doping sulfur ions to modulate wide band gap BiF 3 semiconductor nanospheres. The introduction of sulfur and its combination with bismuth not only enhance light absorption but also introduce oxygen vacancies and the local surface plasmon resonance effect of bismuth. Compared with BiF 3, the band gap is reduced and the carrier separation efficiency is improved. Under the irradiation of a 520 nm laser, electrons reduce oxygen in the process of transition and meanwhile give energy to O 2, producing a large number of reactive oxygen species (ROS). Simultaneously, holes in the valence band oxidize glutathione (GSH), and the coordination effect of the bismuth ion and GSH further depletes GSH. RNA sequencing results reveal the downregulation of GPX4 in tumor cells, inducing ferroptosis. Additionally, sulfide ion doping augmented light absorption, synergizing with light and heat, thereby increasing oxidative damage to the tumor and inhibiting tumor growth. BBSP emerges as a promising strategy for tumor treatment, orchestrating ferroptosis and apoptosis through the combined application of PDT and PTT.