Enhancement of Radio-Thermo-Sensitivity of 5-Iodo-2-Deoxyuridine-Loaded Polymeric-Coated Magnetic Nanoparticles Triggers Apoptosis in U87MG Human Glioblastoma Cancer Cell Line.

Abstract

With an emphasis on the radioresistant nature of glioblastoma cells, the aim of the present study was to evaluate the radio-thermo-sensitizing effects of PCL-PEG-coated Superparamagnetic iron oxide nanoparticles (SPIONs) as a carrier of 5-iodo-2-deoxyuridine (IUdR) in monolayer culture of U87MG human glioma cell line. Following monolayer culture of U87MG cells, nanoparticle uptake was assessed using Prussian blue staining and ICP-OES method. The U87MG cells were treated with an appropriate concentration of free IUdR and PCL-PEG-coated SPIONs (MNPs) loaded with IUdR (IUdR/MNPs) for 24 h, subjected to hyperthermia (water bath and alternating magnetic field (AMF)) at 43°C, and exposed to X-ray (2 Gy, 6 MV). The combined effects of hyperthermia with or without magnetic nanoparticles on radiosensitivity of the U87MG cells were evaluated using colony formation assay (CFA) and Flowcytometry. Prussian blue staining and ICP-OES showed that the nanoparticles were able to enter the cells. The results also indicated that IUdR/MNPs combined with X-ray radiation and hyperthermia significantly decreased the colony formation ability of monolayer cells (1.11, 1.41 fold) and increased the percentage of apoptotic (2.47, 4.1 fold) and necrotic cells (12.28, 29.34 fold), when compared to IUdR combined with X-ray and hyperthermia or IUdR/MNPs + X-ray. MTT results revealed that the presence of IUdR/MNPs significantly increased the toxicity of AMF hyperthermia compared to the water bath method. Our study showed that SPIONs/PCL-PEG, as a carrier of IUdR, can enhance the cytotoxic effects of radiotherapy and hyperthermia and act as a radio-thermo-sensitizing agent. The online version contains supplementary material available at 10.1007/s12195-021-00675-y.