Abstract
In this study, we determined the potential of polyethylene glycol-encapsulated iron oxide nanoparticles (IONPCO) for the intracellular delivery of the chemotherapeutic doxorubicin (IONPDOX) 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. IONPCO radiomodulating effect was dependent on nanoparticle concentration and photon energy. IONPCO did not radiosensitize HeLa cells with 6 MV X-rays, yet moderately enhanced cellular radiosensitivity to 50 kV X-rays (DMFSF0.1 = 1.13 ± 0.05 (p = 0.01)). IONPDOX did enhance the cytotoxicity of 6 MV X-rays (DMFSF0.1 = 1.3 ± 0.1; p = 0.0005). IONP treatment significantly increased γH2AX foci induction without irradiation. Treatment of HeLa cells with IONPCO resulted in a radiosensitizing effect for low-energy X-rays, while exposure to IONPDOX induced radiosensitization compared to IONPCO 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.
Highlights
High-resolution sized to encapsulate thedemonstrated anthracyclinethat doxorubicin
IONPDOX followed by 6 MV X-ray irradiation resulted in a significantly increased clonogenic inactivation compared to both DOX-free iron oxide nanoparticles (IONP) and control cells, with a DMFSF 0.1 = 1.30 ± 0.10. These results suggest that the decrease in clonogenic survival measured after IONPDOX treatment may be due to an interaction of the effects of irradiation with the intracellular released DOX, which is known to interact with and affect the genetic material of the cell and induce the DNA
Our results showed that both IONPCO and IONPDOX increased the number of γH2AX foci in human cervical adenocarcinoma (HeLa) cells without X-ray exposure (Figure 6)
Summary
The current standard multimodal treatment of most cancers consists in the surgical excision of the tumor and a combination of radiotherapy and chemotherapy [1]. In order to minimize systemic adverse effects, targeted therapies involving nanoparticle-based systems have been proposed [2]. In this context, the use of iron oxide nanoparticles (IONP). Is a promising approach to improve the impact of conventional chemo- and radiotherapy in treating cancer. These nanoparticles have been clinically employed in imaging [3,4] and hyperthermia treatment [5,6] of different cancers
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