On the Equivalence of the Biological Effect Induced by Irradiation of Clusters of Heavy Atom Nanoparticles and Homogeneous Heavy Atom-Water Mixtures.
On the Equivalence of the Biological Effect Induced by Irradiation of Clusters of Heavy Atom Nanoparticles and Homogeneous Heavy Atom-Water Mixtures.
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DOI：
10.3390/cancers13092034
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发表时间：
2021-04-23
期刊：
影响因子：
5.2
通讯作者：
Currell FJ
中科院分区：
文献类型：
--
作者：
Villagomez-Bernabe B;Ramos-Méndez J;Currell FJ
纳米粒子在放射治疗中的应用已经被广泛研究了十多年，因为它们能够降低肿瘤细胞的存活率，同时减少在健康细胞中的沉积剂量。在Kev范围内，数学模型成功地再现了文献中的实验结果，但在MV能量范围内发现了差异，后者最常用于放射治疗。这项工作的主要发现是证明了在MV能量范围内纳米粒子簇和金水混合物之间的物理介导的细胞损伤分量的等价性，这降低了在真实情况下看到的辐射与纳米粒子簇相互作用的建模的复杂性。建立了一个基于多尺度局部效应模型(LEM)的研究框架，用于研究临床相关条件下纳米金团簇(GNPs)照射对细胞的损伤。将结果与水和金的均匀混合物(MixNP)在类似条件下照射所得的结果进行了比较。为此，用6 mV直线加速器谱对不同尺寸的GNP团簇和混合NPs进行了蒙特卡罗模拟，计算了水中的剂量增强因子。我们的框架对细胞损伤趋势的预测能力进行了检验和讨论。我们发现，在所有簇的大小下，GNPs簇和MixNP簇之间驱动细胞损伤的主要参数的差异小于1.6%。我们的结果首次证明了一种简单的方法，可以通过考虑等效的均质金/水混合物来直观地了解纳米粒子簇的放射生物学效应。此外，GNPs簇和MixNP簇之间在细胞损伤方面的差异可以忽略不计，简化了纳米粒子聚集体的复杂几何形状的建模，并节省了计算资源。
The use of nanoparticles in radiotherapy has been studied widely for over a decade due to their ability to reduce the survival fraction of tumor cells while reducing the doses deposited in healthy cells. Mathematical models were successfully implemented to reproduce experimental results in the literature at the keV range, but discrepancies were found at the MV energy range, the latter range being most used in radiotherapy. The main finding of this work is the demonstration of an equivalence of the physically mediated component of the cell damage between a cluster of nanoparticles and a gold–water mixture in the MV energy range, which reduces the complexity of modeling the interactions of radiation with clusters of nanoparticles seen in real case scenarios. A multiscale local effect model (LEM)-based framework was implemented to study the cell damage caused by the irradiation of clusters of gold nanoparticles (GNPs) under clinically relevant conditions. The results were compared with those obtained by a homogeneous mixture of water and gold (MixNP) irradiated under similar conditions. To that end, Monte Carlo simulations were performed for the irradiation of GNP clusters of different sizes and MixNPs with a 6 MV Linac spectrum to calculate the dose enhancement factor in water. The capabilities of our framework for the prediction of cell damage trends are examined and discussed. We found that the difference of the main parameter driving the cell damage between a cluster of GNPs and the MixNP was less than 1.6% for all cluster sizes. Our results demonstrate for the first time a simple route to intuit the radiobiological effects of clusters of nanoparticles through the consideration of an equivalent homogenous gold/water mixture. Furthermore, the negligible difference on cell damage between a cluster of GNPs and MixNP simplifies the modelling for the complex geometries of nanoparticle aggregations and saves computational resources.
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