Effect of Gold Nanoparticle Radiosensitization on Plasmid DNA Damage Induced by High-Dose-Rate Brachytherapy.
Effect of Gold Nanoparticle Radiosensitization on Plasmid DNA Damage Induced by High-Dose-Rate Brachytherapy.
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DOI：
10.2147/ijn.s292105
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发表时间：
2021
影响因子：
8
通讯作者：
Yasuda H
中科院分区：
文献类型：
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作者：
Yogo K;Misawa M;Shimizu M;Shimizu H;Kitagawa T;Hirayama R;Ishiyama H;Furukawa T;Yasuda H
金纳米粒子（AuNPs）是用于中等能量光子治疗的候选放射增敏剂，例如高剂量率（HDR）近距离放射治疗中的γ射线辐射。然而，需要高AuNP浓度以用于临床应用的足够剂量增强。在这里，我们研究了带正（+）电荷的AuNP对192 Ir γ射线诱导的质粒DNA损伤的放射增敏作用，并将其与带负（-）电荷的AuNP进行了比较。我们观察到DNA断裂和活性氧（ROS）的产生在低浓度的金纳米粒子的存在下。将pBR 322质粒DNA暴露于64 ng/mL AuNPs，通过HDR近距离放射治疗用192 Ir γ射线照射。通过观察质粒形式的变化检测DNA断裂，并通过琼脂糖凝胶电泳定量。用对ROS敏感的荧光探针测量由AuNPs产生的ROS。比较带正（+）和负（-）电荷的AuNP的效果以研究表面电荷对剂量增强的效果。较低浓度的+AuNP通过产生单链断裂（SSB）和双链断裂（DSB）而促进了与细胞测定和蒙特卡罗模拟实验中使用的那些相当的放射增敏水平。+ AuNP的剂量增强因子（DEF）对于SSB为1.3 ± 0.2，对于DSB为1.5 ± 0.4。+ AuNP增强质粒DNA损伤的能力是由于增强的ROS产生。虽然-AuNP产生类似的活性氧水平，但它们并没有造成显着的DNA损伤。因此，使用低浓度的+AuNP的剂量增强可能通过DNA结合或增加DNA周围的局部+AuNP浓度而发生。与−AuNPs相比，低浓度的+AuNPs表现出更强的放射增敏作用。在HDR近距离放射治疗中将+AuNPs与192 Ir γ射线组合是改善临床结果的候选方法。癌细胞特异性+AuNP的未来开发将允许其更广泛地应用于HDR近距离放射治疗。
Gold nanoparticles (AuNPs) are candidate radiosensitizers for medium-energy photon treatment, such as γ-ray radiation in high-dose-rate (HDR) brachytherapy. However, high AuNP concentrations are required for sufficient dose enhancement for clinical applications. Here, we investigated the effect of positively (+) charged AuNP radiosensitization of plasmid DNA damage induced by 192Ir γ-rays, and compared it with that of negatively (−) charged AuNPs. We observed DNA breaks and reactive oxygen species (ROS) generation in the presence of AuNPs at low concentrations. pBR322 plasmid DNA exposed to 64 ng/mL AuNPs was irradiated with 192Ir γ-rays via HDR brachytherapy. DNA breaks were detected by observing the changes in the form of the plasmid and quantified by agarose gel electrophoresis. The ROS generated by the AuNPs were measured with the fluorescent probe sensitive to ROS. The effects of positively (+) and negatively (−) charged AuNPs were compared to study the effect of surface charge on dose enhancement. +AuNPs at lower concentrations promoted a comparable level of radiosensitization by producing both single-stranded breaks (SSBs) and double-stranded breaks (DSBs) than those used in cell assays and Monte Carlo simulation experiments. The dose enhancement factor (DEF) for +AuNPs was 1.3 ± 0.2 for SSBs and 1.5 ± 0.4 for DSBs. The ability of +AuNPs to augment plasmid DNA damage is due to enhanced ROS generation. While −AuNPs generated similar ROS levels, they did not cause significant DNA damage. Thus, dose enhancement using low concentrations of +AuNPs presumably occurred via DNA binding or increasing local +AuNP concentration around the DNA. +AuNPs at low concentrations displayed stronger radiosensitization compared to −AuNPs. Combining +AuNPs with 192Ir γ-rays in HDR brachytherapy is a candidate method for improving clinical outcomes. Future development of cancer cell-specific +AuNPs would allow their wider application for HDR brachytherapy.