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. 2022 Feb 25;12(5):771.
doi: 10.3390/nano12050771.

Radiosensitization Effect of Gold Nanoparticles on Plasmid DNA Damage Induced by Therapeutic MV X-rays

Katsunori Yogo  1 , Masaki Misawa  2 , Hidetoshi Shimizu  3 , Tomoki Kitagawa  3 , Ryoichi Hirayama  4 , Hiromichi Ishiyama  5 , Hiroshi Yasuda  6 , Satoshi Kametaka  1 , Seiichi Takami  7
Affiliations

Radiosensitization Effect of Gold Nanoparticles on Plasmid DNA Damage Induced by Therapeutic MV X-rays

Katsunori Yogo et al. Nanomaterials (Basel). .

Abstract

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.

Keywords: DNA damage; MV X-rays; gold nanoparticle; positively charged nanoparticle; radiation therapy; radiosensitizer.

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Conflict of interest statement

The authors declare no conflict of interest in this work.

Figures

Figure 1
Figure 1
Illustrations of the dose-enhancement mechanism with low concentrations of positively charged gold nanoparticles (+AuNPs) via +AuNP–DNA binding or increasing the local concentration of +AuNPs around DNA. Positively charged +AuNPs used in combination with 6 MV X-rays increased single- and double-strand breaks in plasmid DNA.
Figure 2
Figure 2
X-ray irradiation setup. (a) Schematic illustration and (b) image of the plastic phantom for the sample holder and X-ray source (gantry of linear accelerator; Linac).
Figure 3
Figure 3
Dose distribution around the sample tube irradiated with 6 MV X-rays. Dose distribution (4 Gy) is presented in the color wash (red) from the side view (a) and the front view (b). Dose distribution was calculated using the treatment planning system.
Figure 4
Figure 4
Scanning transmission electron microscopy (STEM) images of AuNPs: (a) 1.4 nm +AuNPs; (b) 2.0 nm −AuNPs. Scale bar = 10 nm.
Figure 5
Figure 5
Loss of supercoiled plasmid as a function of radiation dose of 6 MV X-rays in the presence of gold nanoparticles (AuNPs).
Figure 6
Figure 6
Increase in linear plasmids as a function of radiation dose of 6 MV X-rays in the presence of gold nanoparticles (AuNPs).
Figure 7
Figure 7
Yields of reactive oxygen species (ROS) as a function of radiation dose of 6 MV X-rays in the presence of gold nanoparticles. ROS yields are evaluated as the fluorescence intensity of the fluorescent probe sensitive to ROS yields.
Figure 8
Figure 8
Light-scattered intensity of +AuNP solution with and without DNA.
See this image and copyright information in PMC

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