Gold nanoparticle (AuNP) radiosensitization represents a novel approach to enhance the effectiveness of ionizing radiation. Its efficiency varies widely with photon source energy and AuNP size, concentration, and intracellular localization. In this Monte Carlo study we explored the effects of those parameters to define the optimal clinical use of AuNPs. Photon sources included (103)Pd and (125)I brachytherapy seeds; (169)Yb, (192)Ir high dose rate sources, and external beam sources 300 kVp and 6 MV. AuNP sizes were 1.9, 5, 30, and 100 nm. We observed a 10(3) increase in the rate of photoelectric absorption using (125)I compared to 6 MV. For a (125)I source, to double the dose requires concentrations of 5.33-6.26 mg g(-1) of Au or 7.10 × 10(4) 30 nm AuNPs per tumor cell. For 6 MV, concentrations of 1560-1760 mg g(-1) or 2.17 × 10(7) 30 nm AuNPs per cell are needed, which is not clinically achievable. Examining the proportion of energy transferred to escaping particles or internally absorbed in the nanoparticle suggests two clinical strategies: the first uses photon energies below the k-edge and takes advantage of the extremely localized Auger cascade. It requires small AuNPs conjugated to tumor targeted moieties and nuclear localizing sequences. The second, using photon sources above the k-edge, requires a higher gold concentration in the tumor region. In this approach, energy deposited by photoelectrons is the main contribution to radiosensitization; AuNP size and cellular localization are less relevant.

Radiosensitization using gold nanoparticles (AuNPs) has been shown to vary widely with cell line, irradiation energy, AuNP size, concentration and intracellular localization. We developed a Monte Carlo-based AuNP radiosensitization predictive model (ARP), which takes into account the detailed energy deposition at the nano-scale. This model was compared to experimental cell survival and macroscopic dose enhancement predictions. PC-3 prostate cancer cell survival was characterized after irradiation using a 300 kVp photon source with and without AuNPs present in the cell culture media. Detailed Monte Carlo simulations were conducted, producing individual tracks of photoelectric products escaping AuNPs and energy deposition was scored in nano-scale voxels in a model cell nucleus. Cell survival in our predictive model was calculated by integrating the radiation induced lethal event density over the nucleus volume. Experimental AuNP radiosensitization was observed with a sensitizer enhancement ratio (SER) of 1.21 ± 0.13. SERs estimated using the ARP model and the macroscopic enhancement model were 1.20 ± 0.12 and 1.07 ± 0.10 respectively. In the hypothetical case of AuNPs localized within the nucleus, the ARP model predicted a SER of 1.29 ± 0.13, demonstrating the influence of AuNP intracellular localization on radiosensitization.