Influence of gold nanoparticles embedded in water on nanodosimetry for keV photon irradiation

Abstract

Purpose: For the past two decades, high-Z nanoparticles have been of high interest to improve the therapeutic outcomes of radiation therapy, especially for low-energy x-rays. Monte Carlo (MC) simulations have been used to evaluate the boost of dose deposition induced by Auger electrons near the nanoparticle surface, by calculating average energy deposition at the nanoscale. In this study, we propose to go beyond average quantities and quantify the stochastic nature of energy deposition at such a scale. We present results of probability density of the specific energy (restricted to ionization, excitation and electron attachment events) in cylindrical nanotargets of height and radius set at 10 nm. This quantity was evaluated for nanotargets located within 200 nm around 5-50 nm gold nanoparticles (GNPs), for 20-90 keV photon irradiation.

Methods: This nanodosimetry study was based on the MC simulation MDM that allows tracking of electrons down to thermalization energy. We introduced a new quantity, namely the probability enhancement ratio (PER), by estimating the probability of imparting to nanotargets a restricted specific energy larger than a threshold $z_0$ (1, 10, and 20 kGy), normalized to the probability for pure water. The PER was calculated as a function of the distance between the nanotarget and the GNP surface. The threshold values were chosen in light of the biophysical model NanOx that predicts cell survival by calculating local lethal events based on the restricted specific energy and an effective local lethal function. $z_0$ then represents a threshold above which the nanotarget damages induce efficiently cell death.

Results: Our calculations showed that the PER varied a lot with the GNP radius, the photon energy, $z_0$ and the distance of the GNP to the nanotarget. The highest PER was 95 when the nanotarget was located at 5 nm from the GNP surface, for a photon energy of 20 keV, a threshold of 20 kGy, and a GNP radius of 50 nm. This enhancement dramatically decreased with increasing GNP-nanotarget distances as it went below 1.5 for distances larger than 200 nm.

Conclusions: The PER seems better adapted than the mean dose deposition to describe the formation of biological damages. The significant increase of the PER within 200 nm around the GNP suggests that severe damages could occur for biological nanotargets located near the GNP. These calculations will be used as an input of the biophysical model NanOx to convert PER into estimation of radiation-induced cell death enhanced by GNPs.

Keywords: Auger electrons; gold nanoparticle; irradiation; nanodosimetry; radiosensitization; radiotherapy.