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

Katsunori Yogo,1 Masaki Misawa,2 Morihito Shimizu,2 Hidetoshi Shimizu,3 Tomoki Kitagawa,3 Ryoichi Hirayama,4 Hiromichi Ishiyama,5 Takako Furukawa,1 Hiroshi Yasuda6 1Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan; 2Health and Medical Research Institute, National Institute of Adva...

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Autores principales:	Yogo K, Misawa M, Shimizu M, Shimizu H, Kitagawa T, Hirayama R, Ishiyama H, Furukawa T, Yasuda H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	gold nanoparticles high-dose-rate brachytherapy dna damage radiosensitization 192ir γ-rays positively charged nanoparticles Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/7db8c86a21d24ddc997f7f2089b79e29
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spelling	oai:doaj.org-article:7db8c86a21d24ddc997f7f2089b79e292021-12-02T14:17:26ZEffect of Gold Nanoparticle Radiosensitization on Plasmid DNA Damage Induced by High-Dose-Rate Brachytherapy1178-2013https://doaj.org/article/7db8c86a21d24ddc997f7f2089b79e292021-01-01T00:00:00Zhttps://www.dovepress.com/effect-of-gold-nanoparticle-radiosensitization-on-plasmid-dna-damage-i-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Katsunori Yogo,1 Masaki Misawa,2 Morihito Shimizu,2 Hidetoshi Shimizu,3 Tomoki Kitagawa,3 Ryoichi Hirayama,4 Hiromichi Ishiyama,5 Takako Furukawa,1 Hiroshi Yasuda6 1Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan; 2Health and Medical Research Institute, National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Ibaraki, Japan; 3Department of Radiation Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan; 4National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba-shi, Chiba, Japan; 5Graduate School of Medical Science, Kitasato University, Sagamihara, Kanagawa, Japan; 6Department of Radiation Biophysics, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, JapanCorrespondence: Katsunori YogoNagoya University Graduate School of Medicine, 1-1-20 Daiko-Minami, Higashi-Ku, Nagoya, Aichi 461-8673, JapanTel +81 52 719 1103Fax +81 52 719 3172Email yogo@met.nagoya-u.ac.jpPurpose: 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: gold nanoparticles, high-dose-rate brachytherapy, DNA damage, radiosensitization, 192Ir γ-rays, positively charged nanoparticlesYogo KMisawa MShimizu MShimizu HKitagawa THirayama RIshiyama HFurukawa TYasuda HDove Medical Pressarticlegold nanoparticleshigh-dose-rate brachytherapydna damageradiosensitization192ir γ-rayspositively charged nanoparticlesMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 359-370 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	gold nanoparticles high-dose-rate brachytherapy dna damage radiosensitization 192ir γ-rays positively charged nanoparticles Medicine (General) R5-920
spellingShingle	gold nanoparticles high-dose-rate brachytherapy dna damage radiosensitization 192ir γ-rays positively charged nanoparticles Medicine (General) R5-920 Yogo K Misawa M Shimizu M Shimizu H Kitagawa T Hirayama R Ishiyama H Furukawa T Yasuda H Effect of Gold Nanoparticle Radiosensitization on Plasmid DNA Damage Induced by High-Dose-Rate Brachytherapy
description	Katsunori Yogo,1 Masaki Misawa,2 Morihito Shimizu,2 Hidetoshi Shimizu,3 Tomoki Kitagawa,3 Ryoichi Hirayama,4 Hiromichi Ishiyama,5 Takako Furukawa,1 Hiroshi Yasuda6 1Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan; 2Health and Medical Research Institute, National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Ibaraki, Japan; 3Department of Radiation Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan; 4National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba-shi, Chiba, Japan; 5Graduate School of Medical Science, Kitasato University, Sagamihara, Kanagawa, Japan; 6Department of Radiation Biophysics, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, JapanCorrespondence: Katsunori YogoNagoya University Graduate School of Medicine, 1-1-20 Daiko-Minami, Higashi-Ku, Nagoya, Aichi 461-8673, JapanTel +81 52 719 1103Fax +81 52 719 3172Email yogo@met.nagoya-u.ac.jpPurpose: 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: gold nanoparticles, high-dose-rate brachytherapy, DNA damage, radiosensitization, 192Ir γ-rays, positively charged nanoparticles
format	article
author	Yogo K Misawa M Shimizu M Shimizu H Kitagawa T Hirayama R Ishiyama H Furukawa T Yasuda H
author_facet	Yogo K Misawa M Shimizu M Shimizu H Kitagawa T Hirayama R Ishiyama H Furukawa T Yasuda H
author_sort	Yogo K
title	Effect of Gold Nanoparticle Radiosensitization on Plasmid DNA Damage Induced by High-Dose-Rate Brachytherapy
title_short	Effect of Gold Nanoparticle Radiosensitization on Plasmid DNA Damage Induced by High-Dose-Rate Brachytherapy
title_full	Effect of Gold Nanoparticle Radiosensitization on Plasmid DNA Damage Induced by High-Dose-Rate Brachytherapy
title_fullStr	Effect of Gold Nanoparticle Radiosensitization on Plasmid DNA Damage Induced by High-Dose-Rate Brachytherapy
title_full_unstemmed	Effect of Gold Nanoparticle Radiosensitization on Plasmid DNA Damage Induced by High-Dose-Rate Brachytherapy
title_sort	effect of gold nanoparticle radiosensitization on plasmid dna damage induced by high-dose-rate brachytherapy
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/7db8c86a21d24ddc997f7f2089b79e29
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Effect of Gold Nanoparticle Radiosensitization on Plasmid DNA Damage Induced by High-Dose-Rate Brachytherapy

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