title: Enhanced production of reactive oxygen species by gadolinium oxide nanoparticles under core-inner-shell excitation by proton or monochromatic X-ray irradiation: implication of the contribution from the interatomic de-excitation-mediated nanoradiator effect to dose enhancement.
abstract: Core-inner-valence ionization of high-Z nanoparticle atomic clusters can de-excite electrons through various interatomic de-excitation processes, thereby leading to the ionization of both directly exposed atoms and adjacent neutral atoms within the nanoparticles, and to an enhancement in photon-electron emission, which is termed the nanoradiator effect. To investigate the nanoradiator-mediated dose enhancement in the radio-sensitizing of high-Z nanoparticles, the production of reactive oxygen species (ROS) was measured in a gadolinium oxide nanoparticle (Gd-oxide NP) solution under core-inner-valence excitation of Gd with either 50 keV monochromatic synchrotron X-rays or 45 MeV protons. This measurement was compared with either a radiation-only control or a gadolinium-chelate magnetic resonance imaging contrast agent solution containing equal amounts of gadolinium as the separate atomic species in which Gd-Gd interatomic de-excitations are absent. Ionization excitations followed by ROS measurements were performed on nanoparticle-loaded cells or aqueous solutions. Both photoexcitation and proton impact produced a dose-dependent enhancement in the production of ROS by a range of factors from 1.6 to 1.94 compared with the radiation-only control. Enhanced production of ROS, by a factor of 1.83, was observed from Gd-oxide NP atomic clusters compared with the Gd-chelate molecule, with a Gd concentration of 48 μg/mL in the core-level photon excitation, or by a factor of 1.82 under a Gd concentration of 12 μg/mL for the proton impact at 10 Gy (p < 0.02). The enhanced production of ROS in the irradiated nanoparticles suggests the potential for additional therapeutic dose enhancements in radiation treatment via the potent Gd-Gd interatomic de-excitation-driven nanoradiator effect.
authors.affiliation: Biomedical Engineering and Radiology, School of Medicine, Catholic University of Daegu, Daegu, Korea.
authors.forename: Seung-Jun
authors.initials: SJ
authors.lastname: Seo
authors.affiliation: Anatomy, School of Medicine, Catholic University of Daegu, Daegu, Korea.
authors.forename: Sung-Mi
authors.initials: SM
authors.lastname: Han
authors.affiliation: Neurosurgery, School of Medicine, Catholic University of Daegu, Daegu, Korea.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Cho
authors.affiliation: High Energy Accelerator Research Organization (KEK), Photon Factory, Tsukuba, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Hyodo
authors.affiliation: Department of Neurosurgery, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Alexander
authors.initials: A
authors.lastname: Zaboronok
authors.affiliation: Shanghai Synchrotron Radiation Facility, Shanghai, China.
authors.forename: He
authors.initials: H
authors.lastname: You
authors.affiliation: Particle Therapy Cancer Research Institute, University of Oxford, Oxford, UK.
authors.forename: Ken
authors.initials: K
authors.lastname: Peach
authors.affiliation: Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford, UK.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hill
authors.affiliation: Biomedical Engineering and Radiology, School of Medicine, Catholic University of Daegu, Daegu, Korea. jkkim@cu.ac.kr.
authors.forename: Jong-Ki
authors.initials: JK
authors.lastname: Kim
mesh_terms: D003287:Contrast Media / Q000737:chemistry / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005682:Gadolinium / Q000737:chemistry* / Q000528:radiation effects*; D018499:Linear Energy Transfer / Q000528:radiation effects; D008422:Materials Testing; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000528:radiation effects* / Q000648:ultrastructure; D011522:Protons; D011829:Radiation Dosage; D017382:Reactive Oxygen Species / Q000138:chemical synthesis* / Q000528:radiation effects*; D012542:Scattering, Radiation; D014965:X-Rays
chemical_list: D003287:Contrast Media; D011522:Protons; D017382:Reactive Oxygen Species; C030581:gadolinium oxide; D005682:Gadolinium
keywords: Inner-shell ionization; Interatomic de-excitation; Low-energy electrons; Nanoparticle atomic clusters; Nanoradiator effect; Radiosensitization; Reactive oxygen species