Yogo Katsunori, Misawa Masaki, Shimizu Hidetoshi, Kitagawa Tomoki, Hirayama Ryoichi, Ishiyama Hiromichi, Yasuda Hiroshi, Kametaka Satoshi, Takami Seiichi
Graduate School of Medicine, Nagoya University, 1-1-20 Daiko-minami, Higashi-ku, Nagoya 461-8673, Japan.
Health and Medical Research Institute, National Institute of Advanced Industrial Science & Technology (AIST), 1-2-1 Namiki, Tsukuba 305-8564, Japan.
Nanomaterials (Basel). 2022 Feb 25;12(5):771. doi: 10.3390/nano12050771.
Gold nanoparticles (AuNPs) can be used with megavolt (MV) X-rays to exert radiosensitization effects, as demonstrated in cell survival assays and mouse experiments. However, the detailed mechanisms are not clear; besides physical dose enhancement, several chemical and biological processes have been proposed. Reducing the AuNP concentration while achieving sufficient enhancement is necessary for the clinical application of AuNPs. Here, we used positively charged (+) AuNPs to determine the radiosensitization effects of AuNPs combined with MV X-rays on DNA damage in vitro. We examined the effect of low concentrations of AuNPs on DNA damage and reactive oxygen species (ROS) generation. DNA damage was promoted by 1.4 nm +AuNP with dose enhancement factors of 1.4 ± 0.2 for single-strand breaks and 1.2 ± 0.1 for double-strand breaks. +AuNPs combined with MV X-rays induced radiosensitization at the DNA level, indicating that the effects were physical and/or chemical. Although -AuNPs induced similar ROS levels, they did not cause considerable DNA damage. Thus, dose enhancement by low concentrations of +AuNPs may have occurred with the increase in the local +AuNP concentration around DNA or via DNA binding. +AuNPs showed stronger radiosensitization effects than -AuNPs. Combining +AuNPs with MV X-rays in radiation therapy may improve clinical outcomes.
金纳米颗粒（AuNPs）可与兆伏（MV）X射线联合使用以发挥放射增敏作用，这在细胞存活试验和小鼠实验中得到了证实。然而，具体机制尚不清楚；除了物理剂量增强外，还提出了几种化学和生物学过程。在实现足够增强效果的同时降低AuNP浓度对于AuNPs的临床应用是必要的。在此，我们使用带正电荷（+）的AuNPs来确定AuNPs与MV X射线联合对体外DNA损伤的放射增敏作用。我们研究了低浓度AuNPs对DNA损伤和活性氧（ROS）生成的影响。1.4 nm的+AuNP促进了DNA损伤，单链断裂的剂量增强因子为1.4±0.2，双链断裂的剂量增强因子为1.2±0.1。+AuNPs与MV X射线联合在DNA水平诱导了放射增敏作用，表明其作用是物理和/或化学性质的。尽管 -AuNPs诱导了相似的ROS水平，但它们并未造成显著的DNA损伤。因此，低浓度+AuNPs的剂量增强可能是由于DNA周围局部+AuNP浓度的增加或通过与DNA结合而发生的。+AuNPs显示出比 -AuNPs更强的放射增敏作用。在放射治疗中将+AuNPs与MV X射线联合使用可能会改善临床疗效。
