Multi-scale Monte Carlo simulations of gold nanoparticle-induced DNA damages for kilovoltage X-ray irradiation in a xenograft mouse model using TOPAS-nBio
Multi-scale Monte Carlo simulations of gold nanoparticle-induced DNA damages for kilovoltage X-ray irradiation in a xenograft mouse model using TOPAS-nBio
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DOI：
10.1186/s12645-021-00099-3
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发表时间：
2021-12-01
影响因子：
5.7
通讯作者：
Multhoff, Gabriele
中科院分区：
文献类型：
--
作者：
Klapproth, Alexander P.;Schuemann, Jan;Multhoff, Gabriele
背景：金纳米颗粒（AuNPs）被认为是一种有前途的药物，以增加肿瘤细胞的放射敏感性。然而，金纳米粒子的辐射增强效应的生物机制仍然没有很好地理解。我们在TOPAS-nBio中提出了一个多尺度Monte Carlo模拟框架，以研究小鼠肿瘤模型中由于AuNPs的存在而导致的DNA损伤的增加。方法：将肿瘤置于体素小鼠模型内，并用100-kVp或200-kVp X射线束照射。采用相空间将粒子从宏观（体素）尺度转移到微观尺度，微观尺度由包括详细的小鼠DNA模型的细胞几何结构组成。在存在和不存在具有由金层包围的Fe 2 O3核的混合纳米颗粒（AuFeNPs）的情况下计算放射增敏效应。为了模拟DNA损伤，即使是非常小的能量轨道，Geant 4-DNA物理和化学模型在微观尺度上使用。结果：AuFeNP诱导的剂量和DNA链断裂的增强已经建立了不同的情况下。产生的化学自由基，包括羟基分子，这被认为是负责通过化学反应的DNA损伤，被发现显着增加。我们进一步观察到200 kVp X射线束的结果对肿瘤内细胞位置的依赖性。结论：我们的多尺度方法允许研究辐射诱导的细胞物理和化学效应。我们发现，相对小浓度的AuFeNPs引起的细胞放射增敏作用可能增加。我们的新方法允许在每个模拟步骤中单独调整参数，因此可用于研究AuFeNPs或AuNPs在活细胞中的放射增敏作用的其他研究。
Background: Gold nanoparticles (AuNPs) are considered as promising agents to increase the radiosensitivity of tumor cells. However, the biological mechanisms of radiation enhancement effects of AuNPs are still not well understood. We present a multi-scale Monte Carlo simulation framework within TOPAS-nBio to investigate the increase of DNA damage due to the presence of AuNPs in mouse tumor models. Methods: A tumor was placed inside a voxel mouse model and irradiated with either 100-kVp or 200-kVp X-ray beams. Phase spaces were employed to transfer particles from the macroscopic (voxel) scale to the microscopic scale, which consists of a cell geometry including a detailed mouse DNA model. Radiosensitizing effects were calculated in the presence and absence of hybrid nanoparticles with a Fe2O3 core surrounded by a gold layer (AuFeNPs). To simulate DNA damage even for very small energy tracks, Geant4-DNA physics and chemistry models were used on microscopic scale. Results: An AuFeNP-induced enhancement of both dose and DNA strand breaks has been established for different scenarios. Produced chemical radicals including hydroxyl molecules, which were assumed to be responsible for DNA damage through chemical reactions, were found to be significantly increased. We further observed a dependency of the results on the location of the cells within the tumor for 200-kVp X-ray beams. Conclusion: Our multi-scale approach allows to study irradiation-induced physical and chemical effects on cells. We showed a potential increase in cell radiosensitization caused by relatively small concentrations of AuFeNPs. Our new methodology allows the individual adjustment of parameters in each simulation step and therefore can be used for other studies investigating the radiosensitizing effects of AuFeNPs or AuNPs in living cells.