Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.
Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Manchester, UK.
Nanoscale. 2017 Nov 30;9(46):18413-18422. doi: 10.1039/c7nr07310k.
Gold nanoparticles have been proven as potential radiosensitizer when combined with protons. Initially the radiosensitization effect was attributed to the physical interactions of radiation with the gold and the production of secondary electrons that induce DNA damage. However, emerging data challenge this hypothesis, supporting the existence of alternative or supplementary radiosensitization mechanisms. In this work we incorporate a realistic cell model with detailed DNA geometry and a realistic gold nanoparticle biodistribution based on experimental data. The DNA single and double strand breaks, and damage complexity are counted under various scenarios of different gold nanoparticle size, biodistribution and concentration, and proton energy. The locality of the effect, i.e. the existence of higher damage at a location close to the gold distribution, is also addressed by investigating the DNA damage at a chromosomal territory. In all the cases we do not observe any significant increase in the single/double strand break yield or damage complexity in the presence of gold nanoparticles under proton irradiation; nor there is a locality to the effect. Our results show for the first time that the physical interactions of protons with the gold nanoparticles should not be considered directly responsible for the observed radiosensitization effect. The model used only accounts for DNA damage from direct interactions, whilst considering the indirect effect, and it is possible the radiosensitization effect to be due to other physical effects, although we consider that possibility unlikely. Our conclusion suggests that other mechanisms might have greater contribution to the radiosensitization effect and further investigation should be conducted.
金纳米颗粒已被证明在与质子结合时是一种潜在的放射增敏剂。最初，放射增敏作用归因于辐射与金的物理相互作用以及产生诱导 DNA 损伤的次级电子。然而，新出现的数据挑战了这一假设，支持存在替代或补充的放射增敏机制。在这项工作中，我们结合了具有详细 DNA 几何形状的现实细胞模型和基于实验数据的现实金纳米颗粒生物分布。在不同金纳米颗粒尺寸、生物分布和浓度以及质子能量的各种情况下，计算了 DNA 的单链和双链断裂以及损伤复杂性。通过研究染色体区域的 DNA 损伤，还解决了效应的局部性，即靠近金分布的位置存在更高损伤的存在。在所有情况下，我们在质子辐照下金纳米颗粒存在的情况下均未观察到单/双链断裂产率或损伤复杂性的任何显着增加；也没有局部效应。我们的结果首次表明，质子与金纳米颗粒的物理相互作用不应被直接视为观察到的放射增敏作用的直接原因。所使用的模型仅考虑了直接相互作用的 DNA 损伤，同时考虑了间接效应，并且放射增敏作用可能归因于其他物理效应，尽管我们认为这种可能性不大。我们的结论表明，其他机制可能对放射增敏作用有更大的贡献，应进行进一步的研究。
