Dependence of gold nanoparticle radiosensitization on cell geometry

Abstract

The radiosensitization effect of gold nanoparticles (GNPs) has been demonstrated both in vitro and in vivo in radiation therapy. The purpose of this study was to systematically assess the biological effectiveness of GNPs distributed in the extracellular media for realistic cell geometries. TOPAS-nBio simulations were used to determine the nanometre-scale radial dose distributions around the GNPs, which were subsequently used to predict the radiation dose response of cells surrounded by GNPs. MDA-MB-231 human breast cancer cells and F-98 rat glioma cells were used as models to assess different cell geometries by changing 1) the cell shape, 2) the nucleus location within the cell, 3) the size of GNPs, and 4) the photon energy. The results show that the sensitivity enhancement ratio (SER) was increased up to a factor of 1.2 when the location of the nucleus is close to the cell membrane for elliptical-shaped cells. Heat-maps of damage-likelihoods show that most of the lethal events occur in the regions of the nuclei closest to the membrane, potentially causing highly clustered damage patterns. The effect of the GNP size on radiosensitization was limited when the GNPs were located outside the cell. The improved modelling of the cell geometry was shown to be crucial because the dose enhancement caused by GNPs falls off rapidly with distance from the GNPs. We conclude that radiosensitization can be achieved for kV photons even without cellular uptake of GNPs when the nucleus is shifted towards the cell membrane. Furthermore, damage was found to concentrate in a small region of the nucleus in close proximity to the extracellular, GNP-laden region.

Comparison of gadolinium nanoparticles and molecular contrast agents for radiation therapy‐enhancement

“…The overall biological effect may be due to cumulative damage on the entire cell (nucleus, membrane and cytoplasm organelles). In a recent publication, Sung et al . have evaluated the influence of the cell shape and nucleus location on dose enhancement produced by AuNPs (2% Au in mass, distributed on the membrane of cells).…”

“…We used a compartmentalized cell model, that consists of a single spherical cell of 10 μ m diameter (the mean diameter of F98 cells was estimated from the fluoroscopy images, see Fig. ) with a 7.5 nm thick membrane and a 4 μ m diameter spherical and centered nucleus.…”

Biodistribution of gold nanoparticles in BBN-induced muscle-invasive bladder cancer in mice

“…For 100 keV electrons, irradiation should result in ranges of tens of microns, but on average the ejected electrons travel much shorter distances -limiting most damage to cells that have either incorporated the gold or are coated by the gold. 18 Importantly, with the amounts of gold that can be delivered to tumors, the overall tumor dose can be increased significantly by a factor of 2-4 times. Administration of AuNPs prior to radiation has been shown to retard tumor growth.…”

Pinhole X-ray fluorescence imaging of gadolinium and gold nanoparticles using polychromatic X-rays: a Monte Carlo study

“…[22][23][24] The low-energy electrons emitted from AuNPs locally deposit their energies in close proximity, which results in physical radiation dose enhancement effect. [22][23][24][25] In addition, the effects of…”