Ultrasmall Bi@Au Schottky Heterojunction with a High Potential Barrier for Amplifying Radioimmunotherapy

Radiotherapy (RT) often has poor clinical sensitivity and tumor metastasis inhibition due to weak X-ray absorption, low energy deposition, inefficient reactive oxygen species (ROS) generation, and induction of antitumor immune response. Here, we report an ultrasmall Bi@Au Schottky heterojunction, namely, Bi@Au nanodots (Bi@Au NDs), to enhance the sensitivity of RT and activate systemic immunity for effective tumor treatment and metastasis inhibition. Bi@Au NDs exhibit a high efficiency of ROS generation and glutathione (GSH) depletion. Density functional theory calculations reveal that Bi@Au NDs with a high Schottky potential barrier can efficiently facilitate carrier separation and prevent carrier backflow, which results in abundant electrons for catalytically decomposing H₂O₂ to ^•OH under X-ray irradiation. Experimental results in vitro and in vivo show that Bi@Au NDs can significantly sensitize RT by enhancing ROS generation and GSH depletion. Bi@Au ND-sensitized RT greatly induces immunogenic cell death and thus promotes a CD8⁺ T cell-mediated systemic immune response, ultimately inhibiting tumor metastasis. Bi@Au NDs as a kind of Schottky heterojunctions can be an effective amplifier for radioimmunotherapy.