Topology-regulated nanocatalysts for ferroptosis-mediated cancer phototherapy

Ferroptosis-mediated tumor treatment is constrained by the absence of single-component, activatable multifunctional inducers. Given this, a topological synthesis strategy is employed to develop an efficient bismuth-based semiconductor nano-photocatalyst (Bi₂O₃:S) for tumor ferroptosis therapy. Photo-excited electrons can participate in the reduction reaction to produce harmful reactive oxygen species (ROS) when exposed to near-infrared light. Meanwhile, photo-excited holes can contribute to the oxidation reaction to utilize extra glutathione (GSH) in tumors. In the acidic tumor microenvironment, bismuth ions generated from Bi₂O₃:S may further cooperate with GSH to amplify oxidative stress damage and achieve biodegradation. Both promote ferroptosis by downregulating glutathione peroxidase 4 (GPX4) expression. Besides, sulfur doping optimizes its near-infrared light-induced photothermal conversion efficiency, benefiting its therapeutic effect. Thus, bismuth ions and holes synergistically drive photo-activable ferroptosis in this nanoplatform, opening up new avenues for tumor therapy.