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.

Coulomb nanoradiator-mediated, site-specific thrombolytic proton treatment with a traversing pristine Bragg peak

“…This ICD process is a common phenomenon34353637 and a direct source of LEEs that may cause radiation damage either directly or via additional ROS production3839404142. Because the atoms in mid/high-Z nanoparticle species are present in typical van der Waals-bonded cluster environments, electron emissions from proton-irradiated IONs occur via both Auger cascades at the directly ionized iron atoms and ICD paths at nearby neutral iron atoms17. The enhancement of the Shirley background in the electron yield from the ION films demonstrated that more LEEs could potentially be produced from the Fe-Fe ICD-present Fe 3 O 4 nanoparticles via the ICD process than by Fe-Fe ICD-absent FeCl 3 .…”

“…The CNR effect is defined as the production of burst emissions of fluorescent X-rays and low-energy electrons (LEEs) via Auger cascades and interatomic/intermolecular Coulomb decay (ICD) paths1314 from mid/high-Z nanoparticles under irradiation by a high-energy ion beam15161718.…”

<p>Ultra-small gadolinium oxide nanocrystal sensitization of non-small-cell lung cancer cells toward X-ray irradiation by promoting cytostatic autophagy</p>

“…Core-inner-valence ionization of GONs can de-excite electrons via potent Gd-Gd interatomic de-excitation processes. 22 Previous studies have revealed the physical or chemical mechanisms of the dose enhancement effects of GONs, but no biological mechanism for GONs has been determined yet. The radiosensitizing biomechanism of GONs under X-ray irradiation remains unclear.…”

Synergistic Effects of Arsenite on Radiosensitization of Glioblastoma Cells

“…Though effects of some metal-related elements on radio-sensitivity have been reported (33)(34)(35), gadolinium (Gd), a metal-related element, has also been reported to have radiosensitizing effects similar to arsenite. Gd mediates the radiosensitizing effect via ROS that is generated from the metal surface, and the characteristics of the radiosensitivity may be similar to those of arsenite (36,37). A phase I clinical trial of combination therapy of arsenite and radiation for patients with solid tumors has been completed, and the safety of arsenite as a clinical drug was proven (38,39).…”