Radiosensitization Effect of Gold Nanoparticles on Plasmid DNA Damage Induced by Therapeutic MV X-rays
Katsunori Yogo,
Masaki Misawa,
Hidetoshi Shimizu,
Tomoki Kitagawa,
Ryoichi Hirayama,
Hiromichi Ishiyama,
Hiroshi Yasuda,
Satoshi Kametaka,
Seiichi Takami
Affiliations
Katsunori Yogo
Graduate School of Medicine, Nagoya University, 1-1-20 Daiko-minami, Higashi-ku, Nagoya 461-8673, Japan
Masaki Misawa
Health and Medical Research Institute, National Institute of Advanced Industrial Science & Technology (AIST), 1-2-1 Namiki, Tsukuba 305-8564, Japan
Hidetoshi Shimizu
Department of Radiation Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan
Tomoki Kitagawa
Department of Radiation Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan
Ryoichi Hirayama
Institute for Quantum Medical Science (iQMS), National Institutes for Quantum Science and Technology (QST), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan
Hiromichi Ishiyama
Graduate School of Medical Science, Kitasato University, 1-15-1 Kitazato, Minami-ku, Sagamihara 252-0374, Japan
Hiroshi Yasuda
Department of Radiation Biophysics, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan
Satoshi Kametaka
Graduate School of Medicine, Nagoya University, 1-1-20 Daiko-minami, Higashi-ku, Nagoya 461-8673, Japan
Seiichi Takami
Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan
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.
