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

Shen, Chuang; Niu, Xianghong; Zhang, Jiaxu; Wang, Shengheng; Chen, Jianwei; Xu, Fei; Duan, Yefan; Zhang, Ying et al. · ACS Nano · 2025

basic_science · Level V

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Abstract

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 H<sub>2</sub>O<sub>2</sub> to <sup>•</sup>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<sup>+</sup> 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.

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