Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Health and Medical Research Institute, National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Ibaraki, Japan.
Int J Nanomedicine. 2021 Jan 14;16:359-370. doi: 10.2147/IJN.S292105. eCollection 2021.
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.
金纳米粒子（AuNPs）是中能光子治疗（如高剂量率（HDR）近距离放射治疗中的γ射线）的候选放射增敏剂。然而，对于临床应用来说，需要高浓度的 AuNP 才能达到足够的剂量增强。在这里，我们研究了正（+）电荷 AuNP 对 192Ir γ 射线诱导的质粒 DNA 损伤的放射增敏作用，并将其与负（-）电荷 AuNP 进行了比较。
我们观察了在低浓度 AuNPs 存在下 DNA 断裂和活性氧（ROS）的产生。用 192Ir γ 射线通过 HDR 近距离放射治疗辐照暴露于 64ng/mL AuNPs 的 pBR322 质粒 DNA。通过观察质粒的形态变化来检测 DNA 断裂，并通过琼脂糖凝胶电泳进行定量。用对 ROS 敏感的荧光探针测量 AuNPs 产生的 ROS。比较正（+）和负（-）电荷 AuNP 的效果，研究表面电荷对剂量增强的影响。
与细胞实验和蒙特卡罗模拟实验中使用的浓度相比，较低浓度的+AuNPs 产生单链断裂（SSBs）和双链断裂（DSBs），从而促进了相当水平的放射增敏作用。+AuNPs 的剂量增强因子（DEF）对于 SSBs 为 1.3±0.2，对于 DSBs 为 1.5±0.4。+AuNPs 增强质粒 DNA 损伤的能力归因于 ROS 生成的增强。虽然 -AuNPs 产生了相似的 ROS 水平，但它们并没有导致明显的 DNA 损伤。因此，使用低浓度的 +AuNPs 进行剂量增强可能是通过 DNA 结合或增加 DNA 周围的局部+AuNP 浓度来实现的。
与 -AuNPs 相比，低浓度的 +AuNPs 表现出更强的放射增敏作用。在 HDR 近距离放射治疗中结合 192Ir γ 射线和 +AuNPs 是提高临床疗效的一种候选方法。开发针对癌细胞的 +AuNPs 将允许更广泛地将其应用于 HDR 近距离放射治疗。
