title: Evaluation of cytotoxicity and radiation enhancement using 1.9 nm gold particles: potential application for cancer therapy.
abstract: High atomic number (Z) materials such as gold preferentially absorb kilovoltage x-rays compared to soft tissue and may be used to achieve local dose enhancement in tumours during treatment with ionizing radiation. Gold nanoparticles have been demonstrated as radiation dose enhancing agents in vivo and in vitro. In the present study, we used multiple endpoints to characterize the cellular cytotoxic response of a range of cell lines to 1.9 nm gold particles and measured dose modifying effects following transient exposure at low concentrations. Gold nanoparticles caused significant levels of cell type specific cytotoxicity, apoptosis and increased oxidative stress. When used as dose modifying agents, dose enhancement factors varied between the cell lines investigated with the highest enhancement being 1.9 in AGO-1522B cells at a nanoparticle concentration of 100 microg ml(-1). This study shows exposure to 1.9 nm gold particles to induce a range of cell line specific responses including decreased clonogenic survival, increased apoptosis and induction of DNA damage which may be mediated through the production of reactive oxygen species. This is the first study involving 1.9 nm nanometre sized particles to report multiple cellular responses which impact on the radiation dose modifying effect. The findings highlight the need for extensive characterization of responses to gold nanoparticles when assessing dose enhancing potential in cancer therapy.
authors.affiliation: Radiation Biology Group, Centre for Cancer Research and Cell Biology, Queen's University Belfast, BT9 7BL, UK. k.butterworth@qub.ac.uk
authors.forename: K T
authors.initials: KT
authors.lastname: Butterworth
authors.forename: J A
authors.initials: JA
authors.lastname: Coulter
authors.forename: S
authors.initials: S
authors.lastname: Jain
authors.forename: J
authors.initials: J
authors.lastname: Forker
authors.forename: S J
authors.initials: SJ
authors.lastname: McMahon
authors.forename: G
authors.initials: G
authors.lastname: Schettino
authors.forename: K M
authors.initials: KM
authors.lastname: Prise
authors.forename: F J
authors.initials: FJ
authors.lastname: Currell
authors.forename: D G
authors.initials: DG
authors.lastname: Hirst
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D048708:Cell Growth Processes / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D006046:Gold / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D017711:Nonlinear Dynamics; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D011838:Radiation-Sensitizing Agents; D006046:Gold