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

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.