Purpose: To deliver a novel tool that significantly improves our understanding of radiobiological implications of gold nanoparticle (GNP) under irradiation and evaluating radiosensitization of GNP.
Methods: An integrated spatialtemporal stochastic simulation framework was developed to simulate radiation transport in cell culture and biological responses of cells. A well-posed, self-consistent cell state transition theory was developed to quantify radiation-induced cellular effects, i.e. radiation-induced cell cycle arrest, and radiation-induced cell death. The cell culture irradiation with GNP using 250 kVp x-ray was simulated, and DNA double strand breaks (DSBs) yield of cells were calculated. Then the DSB information was used to quantify the temporal evolution of cell state transition after irradiation mimicking the cell phenotype evolution of cell survival experiment. The temporal cell phase distribution, and cell survival fraction curve with/without GNP were obtained respectively. The radiosensitization of GNP was quantitatively assessed based on cell phase distribution of and cell survival fraction curve cell culture.
Results: A substantial enhancement in DSB yield was observed when there are GNPs in the cell cytoplasm and this effect increases with larger GNPs. The distance of GNP from nucleus has a large impact on the DSB yield from 200nmâ€“10Î¼m from the cell nucleus. The DSB enhancement ratio ranges from 1.6 to 1.1. Cell cycle progression is severely perturbed under irradiation with GNP. Irradiation with GNP reduces the viable cells undergoing cell proliferation, and substantially increases cell death when dose is over 2 Gy. The simulation result showed that the GNP increase death by up to 30% for the 250 kVp x-ray irradiation.
Conclusion: In this study, we performed a theoretical study for developing and implementing a novel theory for quantifying radiosensitization effect of GNP. By having this novel simulation framework, we can build more realistic, and hence more predictive models of radiotherapy combining GNP.
Not Applicable / None Entered.