Séminaire Jeunes Docteurs du GDR MI2B du 12 avril 2021
Title: Physical, chemical and biological modelling for gold nanoparticle-enhanced radiation therapy: towards a better understanding and optimization of the radiosensitizing effect
In radiation therapy, high-Z nanoparticles such as gold nanoparticles (GNPs) have shown particularly promising radiosensitizing properties. At an early stage, an increase in dose deposition and free radical production throughout the tumor (photoelectric effect) and at sub-cellular scale (Auger cascade) might be responsible for part of the effect for low-energy X-rays. In this work, these early mechanisms are investigated with simulation tools to better quantify them and understand their impact on cell survival.
This work was based on Monte Carlo (MC) models developed to track electrons down to low energy both in water (meV) and gold (eV). In particular, the accuracy of electron transport in gold was assessed by comparing the MC predictions with experimental data in the literature.
Once validated, the MC simulation was used to quantify the energy deposited in nanotargets located near the GNP, which correlates with the probability to generate damages. These nanodosimetry results showed a significant increase of the probability of having an energy deposition in the nanotarget larger than a threshold, within 200 nm around the GNP. This suggests that GNPs may be particularly efficient at destroying biological nanotargets in its vicinity.
The MC simulation was then used to quantify chemical effects. At the macroscale, the increase of free radical production for a concentration of GNPs was calculated. Such increase correlated well with the increase of dose deposition at the macro-scale.
Finally, MC results were used together with the biophysical model NanOx to predict cell survival in presence of GNPs. NanOx was originally developed to calculate the biological dose in hadrontherapy. The Local Effect Model (LEM), currently the main biophysical model implemented for GNP-enhanced radiation therapy, was also used to calculate cell survival and to compare NanOx and LEM predictions. For a simple system where GNPs were homogeneously distributed in the cell, the increase of cell death with the biophysical model NanOx was purely due to the increase of the macroscopic dose. No increased biological effectiveness due to Auger electrons was obtained, which comes in contradiction with the LEM predictions.
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