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Purpose  To introduce the heterogeneous multiscale (Het MS ) model for Monte Carlo simulations of gold nanoparticle dose‐enhanced radiation therapy ( GNPT ), a model characterized by its varying levels of detail on different length scales within a single phantom; to apply the Het MS  model in two different scenarios relevant for  GNPT  and to compare computed results with others published.    Methods  The Het MS  model is implemented using an extended version of the  EGS nrc user‐code egs_chamber; the extended code is tested and verified via comparisons with recently published data from independent  GNP  simulations. Two distinct scenarios for the Het MS  model are then considered: (a) monoenergetic photon beams (20 keV to 1 MeV) incident on a cylinder (1 cm radius, 3 cm length); (b) isotropic point source (brachytherapy source spectra) at the center of a 2.5 cm radius sphere with gold nanoparticles ( GNP s) diffusing outwards from the center. Dose enhancement factors ( DEF s) are compared for different source energies, depths in phantom, gold concentrations,  GNP  sizes, and modeling assumptions, as well as with independently published values. Simulation efficiencies are investigated.    Results  The Het MS MC  simulations account for the competing effects of photon fluence perturbation (due to gold in the scatter media) coupled with enhanced local energy deposition (due to modeling discrete  GNP s within subvolumes).  DEF s are most sensitive to these effects for the lower source energies, varying with distance from the source;  DEF s below unity (i.e., dose decreases, not enhancements) can occur at energies relevant for brachytherapy. For example, in the cylinder scenario, the 20 keV photon source has a  DEF  of 3.1 near the phantom's surface, decreasing to less than unity by 0.7 cm depth (for 20 mg/g). Compared to discrete modeling of  GNP s throughout the gold‐containing (treatment) volume, efficiencies are enhanced by up to a factor of 122 with the Het MS  approach. For the spherical phantom,  DEF s vary with time for diffusion, radionuclide, and radius;  DEF s differ considerably from those computed using a widely applied analytic approach.    Conclusions  By combining geometric models of varying complexity on different length scales within a single simulation, the Het MS  model can effectively account for both macroscopic and microscopic effects which must both be considered for accurate computation of energy deposition and  DEF s for  GNPT . Efficiency gains with the Het MS  approach enable diverse calculations which would otherwise be prohibitively long. The Het MS  model may be extended to diverse scenarios relevant for  GNPT , providing further avenues for research and development.

Heterogeneous multiscale Monte Carlo simulations for gold nanoparticle radiosensitization