Effect of Gold Nanoparticle Radiosensitization on Plasmid DNA Damage Induced by High-Dose-Rate Brachytherapy

Katsunori Yogo; Masaki Misawa; Morihito Shimizu; Hidetoshi Shimizu; Tomoki Kitagawa; Ryoichi Hirayama; Hiromichi Ishiyama; Takako Furukawa; Hiroshi Yasuda

doi:10.2147/IJN.S292105

Effect of Gold Nanoparticle Radiosensitization on Plasmid DNA Damage Induced by High-Dose-Rate Brachytherapy

Int J Nanomedicine. 2021 Jan 14:16:359-370. doi: 10.2147/IJN.S292105. eCollection 2021.

Authors

Katsunori Yogo¹, Masaki Misawa², Morihito Shimizu², Hidetoshi Shimizu³, Tomoki Kitagawa³, Ryoichi Hirayama⁴, Hiromichi Ishiyama⁵, Takako Furukawa¹, Hiroshi Yasuda⁶

Affiliations

¹ Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
² Health and Medical Research Institute, National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Ibaraki, Japan.
³ Department of Radiation Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.
⁴ National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba-shi, Chiba, Japan.
⁵ Graduate School of Medical Science, Kitasato University, Sagamihara, Kanagawa, Japan.
⁶ Department of Radiation Biophysics, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.

Abstract

Purpose: 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.

Methods: 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.

Results: +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.

Conclusion: +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.

Keywords: 192Ir γ-rays; DNA damage; gold nanoparticles; high-dose-rate brachytherapy; positively charged nanoparticles; radiosensitization.

MeSH terms

Brachytherapy*
Computer Simulation
DNA Damage*
Dose-Response Relationship, Radiation
Gamma Rays
Gold / pharmacology*
Humans
Iridium Radioisotopes / chemistry
Metal Nanoparticles / chemistry*
Metal Nanoparticles / ultrastructure
Monte Carlo Method
Plasmids / genetics*
Radiation-Sensitizing Agents / pharmacology*
Radiotherapy Dosage*
Reactive Oxygen Species / metabolism

Substances

Iridium Radioisotopes
Iridium-192
Radiation-Sensitizing Agents
Reactive Oxygen Species
Gold