Dose enhancement effects to the nucleus and mitochondria from gold nanoparticles in the cytosol.
Dose enhancement effects to the nucleus and mitochondria from gold nanoparticles in the cytosol.
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DOI：
10.1088/0031-9155/61/16/5993
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发表时间：
2016-08-21
影响因子：
3.5
通讯作者：
Kuncic Z
中科院分区：
文献类型：
--
作者：
McNamara AL;Kam WW;Scales N;McMahon SJ;Bennett JW;Byrne HL;Schuemann J;Paganetti H;Banati R;Kuncic Z
金纳米粒子（GNP）已显示出作为放射治疗剂量增强剂的潜力。由于基因组的损伤会影响细胞的活力，因此通常认为GNP必须定位在细胞核内。然而，在实践中，GNP倾向于定位在细胞质中，但似乎仍对细胞具有剂量增强作用。这种效应是否可以归因于应激诱导的生物学机制或对核外细胞靶点的物理损伤仍不清楚。然而，越来越多的证据表明，细胞对辐射的反应也可能受到辐射不直接作用于细胞核时引起的间接过程的影响。考虑到它在细胞中的许多重要功能作用，它可能是一个有效的核外辐射靶点。为了更准确地预测辐射在不同细胞器中的物理效应，我们测量了整个人类淋巴细胞JURKAT细胞以及两个独立的细胞器的全部化学成分;细胞核和细胞核。实验测量发现，所有三种生物材料都具有相似的电离能量~ 70 eV，大大低于液态水的电离能量~ 78 eV。10 - 50千电子伏的入射光子的蒙特卡罗模拟显示，更高的能量沉积和电离数的细胞和细胞器材料相比，液态水。在每种材料中加入1%质量分数的金，当对所有入射光子能量进行平均时，能量沉积增加了约1.8倍。对真实区室化细胞的模拟表明，细胞质中金的存在增加了线粒体体积中的能量沉积，而不是核体积中的能量沉积。我们发现这是由于光电子的能量的亚微米离域，使得线粒体成为定位于细胞质的GNP的潜在可行的间接辐射靶。
Gold nanoparticles (GNPs) have shown potential as dose enhancers for radiation therapy. Since damage to the genome affects the viability of a cell, it is generally assumed that GNPs have to localise within the cell nucleus. In practice, however, GNPs tend to localise in the cytoplasm yet still appear to have a dose enhancing effect on the cell. Whether this effect can be attributed to stress-induced biological mechanisms or to physical damage to extra-nuclear cellular targets is still unclear. There is however growing evidence to suggest that the cellular response to radiation can also be influenced by indirect processes induced when the nucleus is not directly targeted by radiation. The mitochondrion in particular may be an effective extra-nuclear radiation target given its many important functional roles in the cell. To more accurately predict the physical effect of radiation within different cell organelles, we measured the full chemical composition of a whole human lymphocytic JURKAT cell as well as two separate organelles; the cell nucleus and the mitochondrion. The experimental measurements found that all three biological materials had similar ionisation energies ~ 70 eV, substantially lower than that of liquid water ~ 78 eV. Monte Carlo simulations for 10 – 50 keV incident photons showed higher energy deposition and ionisation numbers in the cell and organelle materials compared to liquid water. Adding a 1% mass fraction of gold to each material increased the energy deposition by a factor of ~ 1.8 when averaged over all incident photon energies. Simulations of a realistic compartmentalised cell show that the presence of gold in the cytosol increases the energy deposition in the mitochondrial volume more than within the nuclear volume. We find this is due to sub-micron delocalisation of energy by photoelectrons, making the mitochondria a potentially viable indirect radiation target for GNPs that localise to the cytosol.