Composition tunability of semiconductor radiosensitizers for low-dose X-ray induced photodynamic therapy

Radiation therapy is one of the most commonly used methods in clinical cancer treatment, and radiosensitizers could achieve enhanced therapeutic efficacy by incorporating heavy elements into structures. However, the secondary excitation of these high-Z elements-doped nanosensitizers still imply intrinsic defects of low efficiency. Herein, we designed Bi-doped titanium dioxide nanosensitizers in which high-Z Bi ions with adjustable valence state (Bi³⁺ or Bi⁴⁺) replaced some positions of Ti⁴⁺ of anatase TiO₂, increasing both X-rays absorption and oxygen vacancies. The as-prepared TiO₂:Bi nanosensitizers indicated high ionizing radiation energy-transfer efficiency and photocatalytic activity, resulting in efficient electron-hole pair separation and reactive oxygen species production. After further modification with cancer cell targeting peptide, the obtained nanoplatform demonstrated good performance in U87MG cell uptakes and intracellular radicals-generation, severely damaging the vital subcellular organs of U87MG cells, such as mitochondrion, membrane lipid, and nuclei etc. These combined therapeutic actions mediated by the composition-tunable nanosensitizers significantly inhibited the U87MG tumor growth, providing a refreshing strategy for X-ray induced dynamic therapy of malignant tumors.