The synergistic radiosensitizing effect of tirapazamine-conjugated gold nanoparticles on human hepatoma HepG2 cells under X-ray irradiation

Xi Liu,1–4 Yan Liu,1–4 Pengcheng Zhang,1–4 Xiaodong Jin,1–3 Xiaogang Zheng,1–4 Fei Ye,1–4 Weiqiang Chen,1–3 Qiang Li1–3 1Institute of Modern Physics, 2Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese...

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Autores principales: Liu X, Liu Y, Zhang P, Jin X, Zheng X, Ye F, Chen W, Li Q
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Publicado: Dove Medical Press 2016
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spelling oai:doaj.org-article:04e081637f274b519080812d5434a3122021-12-02T04:03:04ZThe synergistic radiosensitizing effect of tirapazamine-conjugated gold nanoparticles on human hepatoma HepG2 cells under X-ray irradiation1178-2013https://doaj.org/article/04e081637f274b519080812d5434a3122016-07-01T00:00:00Zhttps://www.dovepress.com/the-synergistic-radiosensitizing-effect-of-tirapazamine-conjugated-gol-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xi Liu,1–4 Yan Liu,1–4 Pengcheng Zhang,1–4 Xiaodong Jin,1–3 Xiaogang Zheng,1–4 Fei Ye,1–4 Weiqiang Chen,1–3 Qiang Li1–3 1Institute of Modern Physics, 2Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, 3Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou, 4School of Life Science, University of Chinese Academy of Sciences, Beijing, People’s Republic of China Abstract: Reductive drug-functionalized gold nanoparticles (AuNPs) have been proposed to enhance the damage of X-rays to cells through improving hydroxyl radical production by secondary electrons. In this work, polyethylene glycol-capped AuNPs were conjugated with tirapazamine (TPZ) moiety, and then thioctyl TPZ (TPZs)-modified AuNPs (TPZs-AuNPs) were synthesized. The TPZs-AuNPs were characterized by transmission electron microscopy, ultraviolet-visible spectra, dynamic light scattering, and inductively coupled plasma mass spectrometry to have a size of 16.6±2.1 nm in diameter and a TPZs/AuNPs ratio of ~700:1. In contrast with PEGylated AuNPs, the as-synthesized TPZs-AuNPs exhibited 20% increment in hydroxyl radical production in water at 2.0 Gy, and 19% increase in sensitizer enhancement ratio at 10% survival fraction for human hepatoma HepG2 cells under X-ray irradiation. The production of reactive oxygen species in HepG2 cells exposed to X-rays in vitro demonstrated a synergistic radiosensitizing effect of AuNPs and TPZ moiety. Thus, the reductive drug-conjugated TPZs-AuNPs as a kind of AuNP radiosensitizer with low gold loading provide a new strategy for enhancing the efficacy of radiation therapy. Keywords: AuNPs, radiation enhancement, synergistic effect, human hepatoma cells, hydroxyl radical productionLiu XLiu YZhang PJin XZheng XYe FChen WLi QDove Medical Pressarticlegold nanoparticles (AuNPs)radiation enhancementsynergistic effecthuman hepatoma cellshydroxyl radical productionMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 3517-3531 (2016)
institution DOAJ
collection DOAJ
language EN
topic gold nanoparticles (AuNPs)
radiation enhancement
synergistic effect
human hepatoma cells
hydroxyl radical production
Medicine (General)
R5-920
spellingShingle gold nanoparticles (AuNPs)
radiation enhancement
synergistic effect
human hepatoma cells
hydroxyl radical production
Medicine (General)
R5-920
Liu X
Liu Y
Zhang P
Jin X
Zheng X
Ye F
Chen W
Li Q
The synergistic radiosensitizing effect of tirapazamine-conjugated gold nanoparticles on human hepatoma HepG2 cells under X-ray irradiation
description Xi Liu,1–4 Yan Liu,1–4 Pengcheng Zhang,1–4 Xiaodong Jin,1–3 Xiaogang Zheng,1–4 Fei Ye,1–4 Weiqiang Chen,1–3 Qiang Li1–3 1Institute of Modern Physics, 2Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, 3Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou, 4School of Life Science, University of Chinese Academy of Sciences, Beijing, People’s Republic of China Abstract: Reductive drug-functionalized gold nanoparticles (AuNPs) have been proposed to enhance the damage of X-rays to cells through improving hydroxyl radical production by secondary electrons. In this work, polyethylene glycol-capped AuNPs were conjugated with tirapazamine (TPZ) moiety, and then thioctyl TPZ (TPZs)-modified AuNPs (TPZs-AuNPs) were synthesized. The TPZs-AuNPs were characterized by transmission electron microscopy, ultraviolet-visible spectra, dynamic light scattering, and inductively coupled plasma mass spectrometry to have a size of 16.6±2.1 nm in diameter and a TPZs/AuNPs ratio of ~700:1. In contrast with PEGylated AuNPs, the as-synthesized TPZs-AuNPs exhibited 20% increment in hydroxyl radical production in water at 2.0 Gy, and 19% increase in sensitizer enhancement ratio at 10% survival fraction for human hepatoma HepG2 cells under X-ray irradiation. The production of reactive oxygen species in HepG2 cells exposed to X-rays in vitro demonstrated a synergistic radiosensitizing effect of AuNPs and TPZ moiety. Thus, the reductive drug-conjugated TPZs-AuNPs as a kind of AuNP radiosensitizer with low gold loading provide a new strategy for enhancing the efficacy of radiation therapy. Keywords: AuNPs, radiation enhancement, synergistic effect, human hepatoma cells, hydroxyl radical production
format article
author Liu X
Liu Y
Zhang P
Jin X
Zheng X
Ye F
Chen W
Li Q
author_facet Liu X
Liu Y
Zhang P
Jin X
Zheng X
Ye F
Chen W
Li Q
author_sort Liu X
title The synergistic radiosensitizing effect of tirapazamine-conjugated gold nanoparticles on human hepatoma HepG2 cells under X-ray irradiation
title_short The synergistic radiosensitizing effect of tirapazamine-conjugated gold nanoparticles on human hepatoma HepG2 cells under X-ray irradiation
title_full The synergistic radiosensitizing effect of tirapazamine-conjugated gold nanoparticles on human hepatoma HepG2 cells under X-ray irradiation
title_fullStr The synergistic radiosensitizing effect of tirapazamine-conjugated gold nanoparticles on human hepatoma HepG2 cells under X-ray irradiation
title_full_unstemmed The synergistic radiosensitizing effect of tirapazamine-conjugated gold nanoparticles on human hepatoma HepG2 cells under X-ray irradiation
title_sort synergistic radiosensitizing effect of tirapazamine-conjugated gold nanoparticles on human hepatoma hepg2 cells under x-ray irradiation
publisher Dove Medical Press
publishDate 2016
url https://doaj.org/article/04e081637f274b519080812d5434a312
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