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In this study, we determined the potential of polyethylene glycol-encapsulated iron oxide nanoparticles (IONP CO ) for the intracellular delivery of the chemotherapeutic doxorubicin (IONP DOX ) to enhance the cytotoxic effects of ionizing radiation. The biological effects of IONP and X-ray irradiation (50 kV and 6 MV) were determined in HeLa cells using the colony formation assay (CFA) and detection of γH2AX foci. Data are presented as mean ± SEM. IONP were efficiently internalized by HeLa cells. IONP CO radiomodulating effect was dependent on nanoparticle concentration and photon energy. IONP CO did not radiosensitize HeLa cells with 6 MV X-rays, yet moderately enhanced cellular radiosensitivity to 50 kV X-rays (DMF SF0.1 = 1.13 ± 0.05 ( p = 0.01)). IONP DOX did enhance the cytotoxicity of 6 MV X-rays (DMF SF0.1 = 1.3 ± 0.1; p = 0.0005). IONP treatment significantly increased γH2AX foci induction without irradiation. Treatment of HeLa cells with IONP CO resulted in a radiosensitizing effect for low-energy X-rays, while exposure to IONP DOX induced radiosensitization compared to IONP CO in cells irradiated with 6 MV X-rays. The effect did not correlate with the induction of γH2AX foci. Given these results, IONP are promising candidates for the controlled delivery of DOX to enhance the cytotoxic effects of ionizing radiation.

Intracellular Delivery of Doxorubicin by Iron Oxide-Based Nano-Constructs Increases Clonogenic Inactivation of Ionizing Radiation in HeLa Cells