Abstract
To investigate the radiosensitization properties of gold nanoparticles (GNPs) and better understand the intricate deoxyribonucleic acid (DNA) damage induction mechanisms involved in GNP-aided radiotherapy, a single cell model with complete human genome based on the Geant4 Monte Carlo toolkit was applied. A Geant4-DNA model was implemented to simulate direct and indirect DNA damage generated in the physical and chemical stages. In the physical stage, a mixed-physics approach was taken by using Geant4-DNA in water and Livermore in gold. Water radiolysis was created posteriorly in the physicochemical and chemical stages to simulate indirect damage from reactions between DNA molecules and OH• radicals. A mono-energetic photon beam (100keV) and two clinical photon sources (250-kVp, 6-MV flattening-filter free) were simulated for modeling the irradiation of a single cell with or without GNPs. In order to study the effects of GNP size on radiosensitization, 15, 30, and 100nm GNPs were simulated. The effects of intracellular distribution were simulated using 90-nm GNPs with different characteristics of distribution within the cell. The time dependence of DNA damage enhancement was also studied with chemistry stage simulation end-time no larger than 10ns. Double strand break (DSB) enhancement due to direct and indirect action was quantified under different scenarios. Under realistic cellular uptake condition, the 100-nm GNPs had the most significant increase in DSBs: 40.9% and 28.5% for 100keV and 250-kVp photon irradiation, respectively. The intracellular localization showed differing levels of radiosensitization with a maximum of 64%, 27%, and 6% DSB enhancements for 100keV, 250-kVp, and 6-MV respectively, when 90-nm GNPs congregate around the nucleus. The results indicate that photon energy, GNP size, and intracellular distribution play an important role in the enhancement of DSB from direct and indirect damage under scenarios close to cell experiments. The radiosensitization effects due to indirect damage are significant and should be considered carefully.
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