Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Nanoscale. 2017 May 11;9(18):5843-5853. doi: 10.1039/c7nr01024a.
The radiosensitization effect of gold nanoparticles (GNPs) has been demonstrated both in vitro and in vivo in radiation therapy. The purpose of this study was to systematically assess the biological effectiveness of GNPs distributed in the extracellular media for realistic cell geometries. TOPAS-nBio simulations were used to determine the nanometre-scale radial dose distributions around the GNPs, which were subsequently used to predict the radiation dose response of cells surrounded by GNPs. MDA-MB-231 human breast cancer cells and F-98 rat glioma cells were used as models to assess different cell geometries by changing (1) the cell shape, (2) the nucleus location within the cell, (3) the size of GNPs, and (4) the photon energy. The results show that the sensitivity enhancement ratio (SER) was increased up to a factor of 1.2 when the location of the nucleus is close to the cell membrane for elliptical-shaped cells. Heat-maps of damage-likelihoods show that most of the lethal events occur in the regions of the nuclei closest to the membrane, potentially causing highly clustered damage patterns. The effect of the GNP size on radiosensitization was limited when the GNPs were located outside the cell. The improved modelling of the cell geometry was shown to be crucial because the dose enhancement caused by GNPs falls off rapidly with distance from the GNPs. We conclude that radiosensitization can be achieved for kV photons even without cellular uptake of GNPs when the nucleus is shifted towards the cell membrane. Furthermore, damage was found to concentrate in a small region of the nucleus in close proximity to the extracellular, GNP-laden region.
金纳米颗粒（GNPs）的放射增敏作用已在体外和体内放射治疗中得到证实。本研究的目的是系统评估分布在细胞外介质中的 GNPs 对实际细胞几何形状的生物学效应。TOPAS-nBio 模拟用于确定 GNPs 周围纳米尺度的径向剂量分布，随后用于预测被 GNPs 包围的细胞的辐射剂量反应。使用 MDA-MB-231 人乳腺癌细胞和 F-98 大鼠神经胶质瘤细胞作为模型，通过改变（1）细胞形状、（2）细胞核在细胞内的位置、（3）GNPs 的大小和（4）光子能量来评估不同的细胞几何形状。结果表明，当核位于靠近细胞膜的位置时，对于椭圆形细胞，敏感性增强比（SER）最高可增加到 1.2 倍。损伤可能性的热点图表明，大多数致命事件发生在与膜最接近的核区域，可能导致高度聚集的损伤模式。当 GNPs 位于细胞外时，GNPs 大小对放射增敏的影响有限。细胞几何形状的改进建模被证明是至关重要的，因为 GNPs 引起的剂量增强随与 GNPs 的距离迅速下降。我们得出结论，即使当核被推向细胞膜时，对于 kV 光子，即使没有 GNPs 的细胞摄取，也可以实现放射增敏。此外，发现损伤集中在靠近细胞外富含 GNPs 的区域的核的小区域中。
