title: DNA damage enhancement from gold nanoparticles for clinical MV photon beams.
abstract: In this study, we quantify the relative damage enhancement due to the presence of gold nanoparticles (GNP) in vitro in a clinical 6 MV beam for various delivery parameters and depths. It is expected that depths and delivery modes that produce a larger proportions of low-energy photons will have a larger effect on the cell samples containing GNP. HeLa cells with and without 50 nm GNP were irradiated at depths of 1.5, 5, 10, 15 and 20 cm. Conventional beams with square aperture sizes 5, 10 and 15 cm at isocenter, and flattening filter free (FFF) beams were used. Relative DNA damage enhancement with GNP was evaluated by γ-H2AX staining. Statistically significant increases in DNA damage with GNP, compared to the absence of GNP, were observed for all depths and delivery modes. Relative to the shallowest depth, damage enhancement was observed to increase as a function of increasing depth for all deliveries. For the conventional (open field) delivery, DNA damage enhancement with GNP was seen to increase as a function of field size. For FFF delivery, a substantial increase in enhancement was found relative to the conventional field delivery. The measured relative DNA damage enhancement validates the theoretically predicted trends as a function of depth and delivery mode for clinical MV photon beams. The results of this study open new possibilities for the clinical development of gold nanoparticle-aided radiation therapy.
authors.affiliation: Department of Radiation Oncology, Division of Medical Physics and Biophysics, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA. rberbeco@lroc.harvard.edu
authors.forename: Ross I
authors.initials: RI
authors.lastname: Berbeco
authors.forename: Houari
authors.initials: H
authors.lastname: Korideck
authors.forename: Wilfred
authors.initials: W
authors.lastname: Ngwa
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
authors.forename: Janki
authors.initials: J
authors.lastname: Patel
authors.forename: Srinivas
authors.initials: S
authors.lastname: Sridhar
authors.forename: Sarah
authors.initials: S
authors.lastname: Johnson
authors.forename: Brendan D
authors.initials: BD
authors.lastname: Price
authors.forename: Alec
authors.initials: A
authors.lastname: Kimmelman
authors.forename: G Mike
authors.initials: GM
authors.lastname: Makrigiorgos
mesh_terms: D004249:DNA Damage; D006046:Gold / Q000737:chemistry* / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D053768:Metal Nanoparticles; D017785:Photons / Q000627:therapeutic use*
chemical_list: D006046:Gold