Titanium Dioxide Nanoparticles Enhance Radiation Response in Triple-Negative Breast Cancer Cells Under Megavoltage X-Ray Irradiation

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with radioresistance and limited treatment options. Titanium dioxide nanoparticles (TiO2-NPs) have attracted attention as potential radiosensitizers because they can enhance radiation-induced oxidative stress. This study evaluated the radiosensitizing effects of BSA-adsorbed TiO2-NPs in MDA-MB-231 TNBC cells exposed to clinically relevant 6 MV X-ray irradiation. FITC-based cellular association, as an indicator of potential nanoparticle uptake, metabolic activity, clonogenic survival, sensitizer enhancement ratio (SER), reactive oxygen species (ROS), γ-H2AX positivity, and apoptosis were assessed. Flow cytometric analysis showed that approximately 55% of cells were FITC-positive after 24 h of exposure, while approximately 90% metabolic activity was maintained at the selected concentration (25 µg/mL). Combined treatment significantly reduced the surviving fraction from 0.81 to 0.37 after 2 Gy irradiation and yielded SER values of 1.21 and 1.59 at SER10 and SER37, respectively. In addition, combined treatment produced the greatest increases in intracellular ROS generation, γ-H2AX positivity, and apoptosis compared with either treatment alone. These findings indicate that BSA-adsorbed TiO2-NPs increase the radiosensitivity of TNBC cells under clinically relevant megavoltage irradiation and support their further evaluation as potential radiosensitizers for breast cancer radiotherapy.