Energy Dependence of Gold Nanoparticle Radiosensitization in Plasmid DNA

Abstract

Gold nanoparticles (GNPs) are of considerable interest for use as a radiosensitizer, because of their biocompatibility and their ability to increase dose deposited because of their high mass energy absorption coefficient. Their sensitizing properties have been verified experimentally, but a discrepancy between the experimental results and theoretical predictions suggests that the sensitizing effect does not depend solely on gold’s superior absorption of energetic photons. This work presents the results of three sets of experiments that independently mapped out the energy dependence of the radiosensitizing effects of GNPs on plasmid DNA suspended in water. Incident photon energy was varied from 11.8 to 80 keV through the use of monochromatic synchrotron and broadband X-rays. These results depart significantly from the theoretical predictions in two ways: First, the sensitization is significantly larger than would be predicted; second, it does not vary with energy as would be predicted from energy absorption coefficients. These results clearly demonstrate that the effects of GNP-enhanced therapies cannot be predicted by considering additional dose alone and that a greater understanding of the processes involved is necessary for the development of future therapeutics.

Optimal energy for cell radiosensitivity enhancement by gold nanoparticles using synchrotron-based monoenergetic photon beams

“…McMahon et al also suggest that there is reduced radiosensitization in the megavoltage range of energy compared with the kilovoltage range of energy, but the reduction is not as great as that predicted theoretically. 19 Variation in biological processes may contribute to the level of radiosensitization in the megavoltage range of energy, as indicated in the literature. 4,17 The data indicate significant changes in the alpha value, while minimal variations are observed in the beta parameter.…”

“…15,18 However, McMahon et al point out that the difference between kV and mV results is less than 2% and biological factors need to be considered. 19 Supported by a local effect model, McMahon et al suggest that dose enhancement at higher energy levels can be achieved via production of high LET (linear energy transfer) secondary charged particles from the primary interaction of photons with nanoparticles. 19 Experimental work by the same group on the energy dependence of gold nanoparticle radiosensitization yielded results that departed significantly from the theoretical calculations, suggesting that the process of radiosensitization is complex and depends on various factors.…”

“…19 Supported by a local effect model, McMahon et al suggest that dose enhancement at higher energy levels can be achieved via production of high LET (linear energy transfer) secondary charged particles from the primary interaction of photons with nanoparticles. 19 Experimental work by the same group on the energy dependence of gold nanoparticle radiosensitization yielded results that departed significantly from the theoretical calculations, suggesting that the process of radiosensitization is complex and depends on various factors. Recently, a stochastic model of radiation dose enhancement has been described, representing the interactions of incident photons with aggregates of nanoparticles in cells.…”

“…For example, McMahon et al investigated the optimal energy for gold nanoparticles by using plasmid DNA and gamma H2AX foci to observe the DNA damage. 4,19,23 It is very important to understand every part of the cellular effects and interaction with gold nanoparticles; however, the quantifying dose enhancement or radiosensitizing effect essentially arises from the total damage effects of the biological system. Therefore, more multiparametric approaches to measurement that take into account all the biological damage contributing to the radiosensitization effects must be carried out.…”

Nanomaterials: Impact on Cells and Cell Organelles

“…Associated with this process is a massive increase in the local dose (e.g. from a few Gy to 100,000 Gy) [ 7 ].…”