Purpose: Heat generated by magnetic nanoparticle clusters (MNCs) in an alternating magnetic field (AMF) can be used for hyperthermia cancer treatment. Here, we have synthesised polyacrylic acid-coated MNCs according to previous report, with the ability to increase particle stability in suspension. Radiosensitisation effects of the MNCs under an AMF were investigated in vitro and in vivo.
Materials and methods: MTT assay, flow cytometry, clone formation assay, Western blotting, and a γ-H2AX experiment were used to explore the biocompatibility and radiosensitisation effect of the MNCs and their putative radiosensitisation mechanism. An NCI-H460 mouse xenograft model was used to investigate the anti-tumour effect under an AMF in vivo.
Results: The temperature of MNC fluids at different concentrations (200 μg/mL to 2 mg/mL) increased rapidly. The MNCs were endocytosed by the cells and were found to be biocompatible. Hsp70 and caspase-3 were found to be up-regulated upon MNCs under an AMF, radiation, and combination of both treatments. MNCs under an AMF efficiently radiosensitised both CNE-2 cells and NCI-H460 cells. Finally, the tumour inhibition rate after treatment with MNCs under an AMF and radiation was significantly higher than that after either treatment alone. The mechanism of radiosensitisation putatively involves inhibition of DNA repair and induction of apoptosis.
Conclusions: The MNC fluids under an AMF enhanced the radiosensitivity of tumour cells both in vitro and in vivo.
Keywords: Biocompatibility; magnetic nanoparticle clusters; radiosensitisation.