Sensitization of glioblastoma cancer cells to radiotherapy and magnetic hyperthermia by targeted temozolomide-loaded magnetite tri-block copolymer nanoparticles as a nanotheranostic agent

Recently, the development of new strategies in the treatment and diagnosis of cancer cells such as thermo-radiation-sensitizer and theranostic agents have received a great deal of attention. In this work, folic acid-conjugated temozolomide-loaded [email protected] nanoparticles (TMZ-MNP-FA NPs) were proposed for use as magnetic resonance imaging (MRI) contrast agents and to enhance the cytotoxic effects of hyperthermia and radiotherapy. Nanoparticles were synthesized by the Nano-precipitation method and their characteristics were determined by dynamic light scattering (DLS), scanning electron microscopy (SEM) and X-ray powder diffraction (XRD). To evaluate the thermo-radio-sensitization effects of NPs, C6 cells were treated with nanoparticles for 24 h and then exposed to 6-MV X-ray radiation. After radiotherapy, the cells were subjected to an alternating magnetic field (AMF) hyperthermia. The therapeutic potential was assessed using clonogenic assay, ROS generation measurement, flow cytometry assay, and qRT-PCR analysis. Also, the diagnostic properties of the nanoparticles were assessed by MRI. MRI scanning indicated that nanoparticles accumulated in C6 cells could be tracked by T2-weighted MR imaging. Colony formation assay proved that TMZ-MNP-FA NPs enhanced the anti-proliferation effects of AMF by 1.94-fold compared to AMF alone (P < 0.0001). Moreover, these NPs improved the radiation effects with a dose enhancement factor of 1.65. All results showed that the combination of carrier-based chemotherapy with hyperthermia and radiotherapy caused a higher anticancer efficacy than single- or two-modality treatments. The nanoparticles advanced in this study can be proposed as the promising theranostic and thermo-radio-sensitizer platform for the diagnosis and tri-modal synergistic cancer therapy.