title: The synergistic radiosensitizing effect of tirapazamine-conjugated gold nanoparticles on human hepatoma HepG2 cells under X-ray irradiation.
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.
authors.affiliation: Institute of Modern Physics; Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences; Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou; School of Life Science, University of Chinese Academy of Sciences, Beijing, People's Republic of China.
authors.forename: Xi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Institute of Modern Physics; Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences; Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou; School of Life Science, University of Chinese Academy of Sciences, Beijing, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Modern Physics; Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences; Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou; School of Life Science, University of Chinese Academy of Sciences, Beijing, People's Republic of China.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Institute of Modern Physics; Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences; Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Jin
authors.affiliation: Institute of Modern Physics; Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences; Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou; School of Life Science, University of Chinese Academy of Sciences, Beijing, People's Republic of China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Institute of Modern Physics; Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences; Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou; School of Life Science, University of Chinese Academy of Sciences, Beijing, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.affiliation: Institute of Modern Physics; Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences; Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Chen
authors.affiliation: Institute of Modern Physics; Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences; Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
mesh_terms: D006046:Gold / Q000737:chemistry; D056945:Hep G2 Cells / Q000187:drug effects / Q000528:radiation effects*; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D011092:Polyethylene Glycols / Q000737:chemistry; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D000077704:Tirapazamine; D014227:Triazines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D059016:Tumor Microenvironment / Q000187:drug effects; D014965:X-Rays
chemical_list: D011838:Radiation-Sensitizing Agents; D014227:Triazines; D000077704:Tirapazamine; D017665:Hydroxyl Radical; D011092:Polyethylene Glycols; D006046:Gold
keywords: AuNPs; human hepatoma cells; hydroxyl radical production; radiation enhancement; synergistic effect