Monte Carlo Modeling of Reactive Oxygen Species Generation In Gold Nanoparticle-Enhanced Flash Radiotherapy
Abstract
Purpose
To investigate the combined effects of gold nanoparticles (GNPs) and ultrahigh dose rate (UHDR) electron beams on reactive oxygen species (ROS) generation under FLASH radiotherapy conditions using Monte Carlo (MC) simulations.
Methods
Geant4-DNA MC simulations were performed to model a spherical water phantom (10 µm diameter) embedded with a single GNP of varying sizes (5, 10, 50, and 100 nm diameter). Incident electron beams with energies of 100 keV and 1 MeV were simulated at ultra-high dose rates (UHDRs) of 60, 100, and 150 Gy/s. ROS yields, including H₃O⁺, OH•, H₂O₂, OH⁻, and H• radicals, were quantified at 10 ns post-irradiation. The yield enhancement factor (YEF) was calculated as the ratio of ROS generated with GNPs to that with water nanoparticles under identical conditions.
Results
Simulations revealed a strong dependence of ROS yield on GNP size, electron energy, and dose rate. For 1 MeV electrons, YEF increased with decreasing GNP size. At 60 Gy/s, the maximum YEF reached ~1.25 at 30 nm from a 5 nm GNP. Increasing UHDR from 60 to 150 Gy/s reduced YEF for small GNPs. For 100 keV electrons, YEF values were lower overall. Across all conditions, YEF declined sharply between 10 nm and 100 nm GNP sizes, indicating self-absorption and reduced secondary electron escape in larger particles. These findings highlight the fact that nanoparticle size and beam energy are dominant factors in optimizing radiosensitization under FLASH conditions.
Conclusion
This study demonstrates that nanoparticle size and beam parameters critically influence ROS generation during FLASH irradiation. Small GNPs under lower UHDR and higher electron energy conditions significantly enhance ROS yield, suggesting a potential strategy to optimize radiosensitization while preserving the normal tissue-sparing benefits of FLASH-RT. These findings provide a useful computational basis for designing nanoparticle-enhanced FLASH therapies and guide future experimental validation.