title: Imaging and radiation effects of gold nanoparticles in tumour cells.
abstract: Gold nanoparticle radiosensitization represents a novel technique in enhancement of ionising radiation dose and its effect on biological systems. Variation between theoretical predictions and experimental measurement is significant enough that the mechanism leading to an increase in cell killing and DNA damage is still not clear. We present the first experimental results that take into account both the measured biodistribution of gold nanoparticles at the cellular level and the range of the product electrons responsible for energy deposition. Combining synchrotron-generated monoenergetic X-rays, intracellular gold particle imaging and DNA damage assays, has enabled a DNA damage model to be generated that includes the production of intermediate electrons. We can therefore show for the first time good agreement between the prediction of biological outcomes from both the Local Effect Model and a DNA damage model with experimentally observed cell killing and DNA damage induction via the combination of X-rays and GNPs. However, the requirement of two distinct models as indicated by this mechanistic study, one for short-term DNA damage and another for cell survival, indicates that, at least for nanoparticle enhancement, it is not safe to equate the lethal lesions invoked in the local effect model with DNA damage events.
authors.affiliation: Centre for Plasma Physics, School of Mathematics and Physics, Queen's University Belfast, Belfast, BT7 1NN, Northern Ireland, UK.
authors.forename: Harold N
authors.initials: HN
authors.lastname: McQuaid
authors.affiliation: Camlin Technologies Ltd. Lisburn, BT28 2EX, N.Ireland, UK.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Muir
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, BT9 7BL, Northern Ireland, UK.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Taggart
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, BT9 7BL, Northern Ireland, UK.|Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: McMahon
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, BT9 7BL, Northern Ireland, UK.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Coulter
authors.affiliation: Northern Ireland Cancer Centre, Belfast Health and Social Care Trust, Belfast, BT9 7AB, UK.
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Hyland
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, BT9 7BL, Northern Ireland, UK.|Northern Ireland Cancer Centre, Belfast Health and Social Care Trust, Belfast, BT9 7AB, UK.
authors.forename: Suneil
authors.initials: S
authors.lastname: Jain
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, BT9 7BL, Northern Ireland, UK.
authors.forename: Karl T
authors.initials: KT
authors.lastname: Butterworth
authors.affiliation: National Physical Laboratory, Hampton Road, Teddington, TW11 0LW, UK.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Schettino
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, BT9 7BL, Northern Ireland, UK.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Prise
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, BT9 7BL, Northern Ireland, UK.
authors.forename: David G
authors.initials: DG
authors.lastname: Hirst
authors.affiliation: Central Laser Facility, Research Complex at Harwell, Science and Technology Facilities Council, Rutherford Appleton Laboratory, Oxfordshire, OX11 0QX, UK.
authors.forename: Stanley W
authors.initials: SW
authors.lastname: Botchway
authors.affiliation: Centre for Plasma Physics, School of Mathematics and Physics, Queen's University Belfast, Belfast, BT7 1NN, Northern Ireland, UK.
authors.forename: Fred J
authors.initials: FJ
authors.lastname: Currell
mesh_terms: D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004249:DNA Damage / Q000528:radiation effects; D006046:Gold; D006801:Humans; D053768:Metal Nanoparticles; D046032:Microscopy, Energy-Filtering Transmission Electron; D057054:Molecular Imaging; D009010:Monte Carlo Method; D011827:Radiation; D011829:Radiation Dosage
chemical_list: D006046:Gold