Article Commentary on "Microdosimetric and radiobiological effects of gold nanoparticles at therapeutic radiation energies" [T.M. Gray et al., IJRB 2023, 99(2), 308-317].

In the recently published article by T.M. Gray et al. "Microdosimetric and radiobiological effects of gold nanoparticles at therapeutic radiation energies" (IJRB 2023, 99(2), 308-317) results of Monte Carlo simulations and radiobiological assays on the dosimetric effects of gold nanoparticles were presented. This commentary points out that the results of the two parts of the study are in contradiction and that the predicted magnitude of dose enhancement and its dependence on the shape of the nanoparticle appear implausible. In particular, the simulations were performed for a lower mass fraction of gold than used in the experiments, and average dose enhancement factors between 2.7 and 8 were predicted (depending on incident radiation and nanoparticle shape). Such dose enhancement would result in orders of magnitude reduction in cell survival. In contrast, only a moderate reduction of cell survival was observed in the radiobiological assays. Furthermore, given the results reported for the average dose enhancement, the reported local dose values appear to be orders of magnitude too low. Finally, a simple geometric consideration shows that the setup used in the microscopic simulations led to a bias in the results that could explain the higher dose enhancement found for cubic compared to spherical nanoparticles.In the second part of this commentary, literature data are used to estimate an upper bound for the dose enhancement factor and the order of magnitude for the local dose around the gold nanoparticles. The upper bound for the dose enhancement is about 1.0055 for the spherical 30-nm gold nanoparticle under consideration irradiated with a 6 MV linac spectrum in the chosen simulation setup. The estimated local dose per photon is on the order of 10 -5 Gy instead of 10 -25 Gy as reported by Gray et al. An analysis of the chord length distributions through the cubic and spherical nanoparticles from a nearby point source (as used by Gray et al.) shows that there is a bias of about 21% in favor of the cubic shape, which explains most of the reported higher dose enhancement found by Gray et al. for the cubic nanoparticle. In addition, a re-analysis of the cell survival data from Gray et al. is performed. This includes uncertainty assessment showing that the deviations between the survival curves for different gold concentration are much smaller than the uncertainties.