Kim Chloe Doen, Chow James C L
Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1X6, Canada.
Department of Radiation Oncology, University of Toronto, Toronto, ON M5T 1P5, Canada.
Nanomaterials (Basel). 2025 Aug 23;15(17):1303. doi: 10.3390/nano15171303.
Ultrahigh dose rate (UHDR) radiotherapy, also known as FLASH radiotherapy (FLASH-RT), has shown potential for increasing tumor control while sparing normal tissue. In parallel, gold nanoparticles (GNPs) have been extensively explored as radiosensitizers due to their high atomic number and ability to enhance the generation of reactive oxygen species (ROS) through water radiolysis. In this study, we investigate the synergistic effects of UHDR electron beams and GNP-mediated radiosensitization using Monte Carlo (MC) simulations based on the Geant4-DNA code. A spherical water phantom with embedded GNPs of varying sizes (5-100 nm) was irradiated using pulsed electron beams (100 keV and 1 MeV) at dose rates of 60, 100, and 150 Gy/s. The chemical yield of ROS near the GNPs was quantified and compared to an equivalent water nanoparticle model, and the yield enhancement factor (YEF) was used to evaluate radiosensitization. Results demonstrated that YEF increased with smaller GNP sizes and at lower UHDR, particularly for 1 MeV electrons. A maximum YEF of 1.25 was observed at 30 nm from the GNP surface for 5 nm particles at 60 Gy/s. The elevated ROS concentration near GNPs under FLASH conditions is expected to intensify DNA damage, especially double-strand breaks, due to increased hydroxyl radical interactions within nanometric distances of critical biomolecular targets. These findings highlight the significance of nanoparticle size and beam parameters in optimizing ROS production for FLASH-RT. The results provide a computational basis for future experimental investigations into the combined use of GNPs and UHDR beams in nanoparticle-enhanced radiotherapy.
超高剂量率（UHDR）放射治疗，也称为FLASH放射治疗（FLASH-RT），已显示出在增加肿瘤控制的同时保护正常组织的潜力。与此同时，金纳米颗粒（GNP）因其高原子序数以及通过水辐射分解增强活性氧（ROS）生成的能力，已被广泛研究作为放射增敏剂。在本研究中，我们使用基于Geant4-DNA代码的蒙特卡罗（MC）模拟，研究了UHDR电子束与GNP介导的放射增敏的协同效应。使用脉冲电子束（100 keV和1 MeV）以60、100和150 Gy/s的剂量率照射嵌入不同尺寸（5-100 nm）GNP的球形水体模。对GNP附近ROS的化学产率进行了量化，并与等效的水纳米颗粒模型进行了比较，产率增强因子（YEF）用于评估放射增敏作用。结果表明，YEF随着GNP尺寸减小和UHDR降低而增加，特别是对于1 MeV电子。在60 Gy/s下，5 nm颗粒在距GNP表面30 nm处观察到最大YEF为1.25。在FLASH条件下，GNP附近升高的ROS浓度预计会加剧DNA损伤，尤其是双链断裂，这是由于关键生物分子靶点纳米距离内的羟基自由基相互作用增加所致。这些发现突出了纳米颗粒尺寸和束参数在优化FLASH-RT的ROS产生中的重要性。这些结果为未来关于在纳米颗粒增强放射治疗中联合使用GNP和UHDR束的实验研究提供了计算基础。
