Physical, chemical and biological modelling of the radiosensitizing effect of high-Z nanoparticles

International audienceBackground: In radiotherapy, the use of radiosensitizers aims at amplifying the destructive effects of the dose in the tumor. High-Z nanoparticles have shown promising radiosensitizing properties that may originate from early physical and chemical mechanisms. A local amplification of the energy deposition inside nanotargets such as DNA, in addition to a boost of free radicals could be responsible for an increase of cell death. While it has been studied for over a decade, the understanding of such effects remains under investigation.Goal: As experimental results appear sometimes contradictory, modelling may help to better understand and quantify these early mechanisms and their impacts on cell survival.Methods: We developed Monte Carlo simulations (MCS) which track secondary electrons down to low energy both in water (meV) and gold (eV). These MCS were used to calculate the two following quantities, for an irradiated volume of water containing nanoparticles:(1) the statistical distribution of energy deposition in nanotargets, and the impact of nanoparticles on this distribution, with regard to the distance of the nanotarget to the nanoparticle surface.(2) the boost of free-radical production induced by nanoparticles, both at macro- and nanoscale.We emphasize that the time for such calculations would be prohibitive (>500 centuries on a PC) without several numerical optimizations. These two results were used in the biophysical model NanOx, originally developed to predict biological dose in hadrontherapy, to quantify the effect of nanoparticles in terms of cell death.Results: The effect of gold nanoparticles on these 3 quantities will be presented for irradiation with 20-90 keV photons, various nanoparticle sizes and concentrations.Conclusion: Nanoparticles increased the probability of energy deposition in nanotargets, especially for high energy deposition, within