Imaging and radiation effects of gold nanoparticles in tumour cells.
Imaging and radiation effects of gold nanoparticles in tumour cells.
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DOI：
10.1038/srep19442
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发表时间：
2016-01-20
影响因子：
4.6
通讯作者：
Currell FJ
中科院分区：
文献类型：
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作者：
McQuaid HN;Muir MF;Taggart LE;McMahon SJ;Coulter JA;Hyland WB;Jain S;Butterworth KT;Schettino G;Prise KM;Hirst DG;Botchway SW;Currell FJ
金纳米粒子辐射增敏是一种提高电离辐射剂量及其对生物系统影响的新技术。理论预测和实验测量之间的差异足够大，导致细胞杀伤率和DNA损伤增加的机制仍然不清楚。我们提供了第一个实验结果，该结果同时考虑了在细胞水平上测量的金纳米颗粒的生物分布以及负责能量沉积的产物电子的范围。结合同步加速器产生的单能X射线、细胞内金粒子成像和DNA损伤分析，已经能够产生包括产生中间电子的DNA损伤模型。因此，我们可以第一次展示从局部效应模型和DNA损伤模型预测的生物学结果之间的良好一致性，该模型具有实验观察到的细胞杀伤和通过X射线和GNPs组合诱导的DNA损伤。然而，这项机制研究表明，需要两个不同的模型，一个用于短期DNA损伤，另一个用于细胞存活，这表明，至少对于纳米颗粒增强来说，将局部效应模型中调用的致命损伤与DNA损伤事件等同起来是不安全的。
Gold nanoparticle radiosensitization represents a novel technique in enhancement of ionising radiation dose and its effect on biological systems. Variation between theoretical predictions and experimental measurement is significant enough that the mechanism leading to an increase in cell killing and DNA damage is still not clear. We present the first experimental results that take into account both the measured biodistribution of gold nanoparticles at the cellular level and the range of the product electrons responsible for energy deposition. Combining synchrotron-generated monoenergetic X-rays, intracellular gold particle imaging and DNA damage assays, has enabled a DNA damage model to be generated that includes the production of intermediate electrons. We can therefore show for the first time good agreement between the prediction of biological outcomes from both the Local Effect Model and a DNA damage model with experimentally observed cell killing and DNA damage induction via the combination of X-rays and GNPs. However, the requirement of two distinct models as indicated by this mechanistic study, one for short-term DNA damage and another for cell survival, indicates that, at least for nanoparticle enhancement, it is not safe to equate the lethal lesions invoked in the local effect model with DNA damage events.