A Universally EDTA-Assisted Synthesis of Polytypic Bismuth Telluride Nanoplates with a Size-Dependent Enhancement of Tumor Radiosensitivity and Metabolism In Vivo

Bismuth telluride (Bi₂Te₃) is an available thermoelectric material with the lowest band gap among bismuth chalcogenides, revealing a broad application in photocatalysis. Unfortunately, its size and morphology related to a radio-catalysis property have rarely been explored. Herein, an ethylenediaminetetraacetic acid (EDTA)-assisted hydrothermal strategy was introduced to synthesize polytypic Bi₂Te₃ nanoplates (BT NPs) that exhibit size-dependent radio-sensitization and metabolism characteristics in vivo. By simply varying the molar ratio of EDTA/Bi³⁺ during the reaction, BT NPs with different sizes and morphologies were obtained. EDTA acting as chelating agent and "capping" agent contributed to the homogeneous growth of BT NPs by eliminating dangling bonds and reducing the surface energy of different facets. Further analyzing the size-dependent radio-sensitization mechanism, larger-sized BT NPs generated holes that preferentially catalyzed the conversion of OH^- to ·OH when irradiated with X-rays, while the smaller-sized BT NPs exhibited faster decay kinetics producing higher ¹O₂ levels to enhance radiotherapy effects. A metabolomic analysis revealed that larger-sized BT NPs were oxidized into Bi(O_x) in the liver via a citrate cycle pathway, whereas smaller-sized BT NPs accumulated in the kidney and were excreted in urine in the form of ions by regulating the metabolism of glutamate. In a cervical cancer model, BT NPs combined with X-ray irradiation significantly antagonized tumor suppression through the promotion of apoptosis in tumor cells. Consequently, in addition to providing a prospect of BT NPs as an efficient radio-sensitizer to boost the tumor radiosensitivity, we put forth a strategy that can be universally applied in synthesizing metal chalcogenides for catalysis-promoted radiotherapy.