Gold Nanoparticles Enhancing Generation of ROS for Cs-137 Radiotherapy

Abstract

Radiotherapy is an important modality for the treatment of cancer, e.g., X-ray, Cs-137 γ-ray (peak energy: 662 keV). An important therapy pathway of radiation is to generate the double strand breaks of DNA to prohibit the proliferation of cancer cells. In addition, the excessive amount of reactive oxygen species (ROS) is induced to damage the organelles, which can cause cellular apoptosis or necrosis. Gold nanoparticles (GNPs) have been proven potential as a radiosensitizer due to the high biocompatibility, the low cytotoxicity and the high-Z property (Z = 79) of gold. The latter property may allow GNPs to induce more secondary electrons for generating ROS in cells as irradiated by high-energy photons. In this paper, the radiobiological effects on A431 cells with uptake of 55-nm GNPs were studied to investigate the GNPs-enhanced production of ROS on these cells as irradiated by Cs-137 γ-ray. The fluorescence-labeling image of laser scanning confocal microscopy (LSCM) shows the excessive expression of ROS in these GNPs-uptake cells after irradiation. And then, the follow-up disruption of cytoskeletons and dysfunction of mitochondria caused by the induced ROS are observed. From the curves of cell survival fraction versus the radiation dose, the radiosensitization enhancement factor of GNPs is 1.29 at a survival fraction of 30%. This demonstrates that the tumoricidal efficacy of Cs-137 radiation can be significantly raised by GNPs. Because of facilitating the production of excessive ROS to damage tumor cells, GNPs are proven to be a prospective radiosensitizer for radiotherapy, particularly for the treatment of certain radioresistant tumor cells. Through this pathway, the tumoricidal efficacy of radiotherapy can be raised.