Advances in modelling gold nanoparticle radiosensitization using new Geant4-DNA physics models

Abstract

Gold nanoparticles have demonstrated significant radiosensitization of cancer treatment with x-ray radiotherapy. To understand the mechanisms at the basis of nanoparticle radiosensitization, Monte Carlo simulations are used to investigate the dose enhancement, given a certain nanoparticle concentration and distribution in the biological medium. Earlier studies have ordinarily used condensed history physics models to predict nanoscale dose enhancement with nanoparticles. This study uses Geant4-DNA complemented with novel track structure physics models to accurately describe electron interactions in gold and to calculate the dose surrounding gold nanoparticle structures at nanoscale level. The computed dose in silico due to a clinical kilovoltage beam and the presence of gold nanoparticles was related to in vitro brain cancer cell survival using the local effect model. The comparison of the simulation results with radiobiological experimental measurements shows that Geant4-DNA and local effect model can be used to predict cell survival in silico in the case of x-ray kilovoltage beams.

Quantification of gold nanoparticle photon radiosensitization from direct and indirect effects using a complete human genome single cell model based on Geant4

“…45 However, a more homogeneously distribution of GNPs in cells can simulate the average GNP distribution surrounding the nucleus to produce a universal estimate about dose enhancement due to the GNPs. This is an appropriate estimate and the reason why gold shell-like geometries have been adopted to approximate the distribution of GNPs as in the work of McKinnon et al 46 and Engels et al, 7 as well as our previous study. 8 Additionally, small GNPs can be taken by nucleus through nuclear pore in practice.…”

“…However, the radiosensitization mechanism of metallic nanomaterials is not well understood, and the accurate prediction of the related biological effects remains a significant challenge in radiobiology research. A number of theoretical models and Monte Carlo (MC) simulations have made signification contributions to better understand and predict these effects [1][2][3][4][5][6][7][8][9] and have been used to investigate the radiosensitization of GNPs for various geometrical parameters and radiation modalities.…”

Review of the Geant4-DNA Simulation Toolkit for Radiobiological Applications at the Cellular and DNA Level

“…The Geant4-DNA models have been tested and validated against reference data (i.e., NIST, ICRU) and wherever available versus experimental data and other MC simulation studies. Comparisons between the condensed history models of Geant4 and the track-structure models of Geant4-DNA have also been undertaken for particular applications [ 14 , 23 , 59 , 60 , 61 , 62 , 63 ].…”

Radiolabeled Gold Nanoseeds Decorated with Substance P Peptides: Synthesis, Characterization and In Vitro Evaluation in Glioblastoma Cellular Models

“…As an example, Figure S17 shows the source emitting in the nucleus and in the culture medium around the cell. The choice of the above irradiation scenarios (single AuNP and gold shell) is largely supported by many studies present in literature [ 52 , 65 ] The single AuNP model mimics a cluster of AuNPs in the nucleus; whereas, the gold shell around the nucleus mimics a preferential AuNPs distribution among the nucleus and cytoplasm, as reported elsewhere [ 65 ].…”