Synergetic radiosensitizing effect of Bi-Tb-doped cerium fluoride nanoparticles under X-ray irradiation on 3D tumor spheroids

Radiotherapy is one of the most effective approaches to treat malignant tumors. Nanoparticles-based technologies are considered to be advanced strategies in radiotherapy due to their ability to both increase effectiveness and decrease side effects of the therapy. Unique physiochemical properties of cerium fluoride nanoparticles are making them prospective radiosensitizers. In this study, radiosensitizing activity of Bi-Tb-doped cerium fluoride nanoparticles (Ce _0.75 Bi _0.15 Tb _0.1 F ₃ NPs) under X-ray irradiation was assessed on a 3D tumor spheroid model, based on EMT6/P cells. We showed a pH-dependent radiocatalytic activity of Ce _0.75 Bi _0.15 Tb _0.1 F ₃ NPs under X-ray irradiation, demonstrating a 40-fold increase in their prooxidant activity under acidic conditions. Radiosensitizing effect of Ce _0.75 Bi _0.15 Tb _0.1 F ₃ NPs was assessed via evaluation of tumor cell migration, viability and clonogenic activity under X-ray irradiation. Combined action of Ce _0.75 Bi _0.15 Tb _0.1 F ₃ NPs (at a concentration of 1 mM) and X-ray irradiation (at a dose of 6 Gy) caused additive effect (coefficient of drug interaction (CDI)=1.02), resulting in a decrease of cell migration from irradiated 3D tumor spheroid. Moreover, the combined treatment decreased both viability and proliferation of tumor cells synergistically (CDI=0.63). Thus, Ce _0.75 Bi _0.15 Tb _0.1 F ₃ NPs demonstrated the synergistic radiosensitizing effect in the 3D tumor spheroid model, suggesting the potential for using these nanoparticles to enhance the effectiveness of tumor radiotherapy.