Reactive oxygen species-based measurement of the dependence of the Coulomb nanoradiator effect on proton energy and atomic Z value

Purpose: The Coulomb nanoradiator (CNR) effect produces the dose enhancement effects from high-Z nanoparticles under irradiation with a high-energy ion beam. To gain insight into the radiation dose and biological significance of the CNR effect, the enhancement of reactive oxygen species (ROS) production from iron oxide or gold NPs (IONs or AuNPs, respectively) in water was investigated using traversing proton beams. Methods and materials: The dependence of nanoradiator-enhanced ROS production on the atomic Z value and proton energy was investigated. Two biologically important ROS species were measured using fluorescent probes specific to (OH)-O-center dot or O-2(center dot-) in a series of water phantoms containing either AuNPs or IONs under irradiation with a 45- or 100-MeV proton beam. Results: The enhanced generation of hydroxyl radicals ((OH)-O-center dot) and superoxide anions (O-2(center dot-)) was determined to be caused by the dependence on the NP concentration and proton energy. The proton-induced Au or iron oxide nanoradiators exhibited different ROS enhancement rates depending on the proton energy, suggesting that the CNR radiation varied. The curve of the superoxide anion production from the Au-nanoradiator showed strong non-linearity, unlike the linear behavior observed for hydroxyl radical production and the X-ray photoelectric nanoradiator. In addition, the 45-MeV proton-induced Au nanoradiator exhibited an ROS enhancement ratio of 8.54/1.50 (O-2(center dot-)/(OH)-O-center dot), similar to that of the 100-KeV X-ray photoelectric Au nanoradiator (7.68/1.46). Conclusions: The ROS-based detection of the CNR effect revealed its dependence on the proton beam energy, dose and atomic Z value and provided insight into the low-linear energy transfer (LET) CNR radiation, suggesting that these factors may influence the therapeutic efficacy via chemical reactivities, transport behaviors, and intracellular oxidative stress.