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

Abstract

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 or 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) and superoxide anions () 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 ( / •OH), 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.

Keywords:

• Coulomb nanoradiator
• ROS
• gold nanoparticle
• iron oxide nanoparticle
• proton irradiation
• fluorescent probe
• dose enhancement

Acknowledgements

The authors thank M. H. Jung of KOMAC, Kyungju, for his help during the irradiation session.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Notes on contributors

Seung-Jun Seo, PhD in Biomedical Engineering from Catholic University, gained a wide range of research experience in synchrotron X-ray imaging and Coulomb nanoradiator therapy. His main areas of expertise are design of targeted high-Z nanoparticle, ROS-based nanoradiator dosimetry, diffraction-based SR X-ray imaging and nanoradiator therapy for brain tumor and retinal disease.

Jae-Kun Jeon currently performs graduate work as a PhD candidate at Catholic University of Daegu. He gained wide experience in nanoradiator study for dosimetry and clinical application using animal model and synthesis of nanoparticles. He is extensively involved in the development of Coulomb nanoradiator therapy for vascular diseases.

Sung-Mi Han obtained her PhD degree in anatomy from the Catholic University of Daegu. She is currently a researcher supporting the University center of Optometry and advanced optical engineering. She had strong experience in synchrotron X-ray nanoscopic imaging study and therapeutic development using Coulomb nanoradiator.

Jong-Ki Kim studied Astronomy and Physics at SNU/KAIST, and PhD in Biophysics from SUNY/Buffalo. He established concept of Coulomb nanoradiator using traversing ion beam. Currently, his main research interests are detection of Interatomic/Intermolecular coulomb decay electron emission in high-Z nanoparticles, and supervising the development of CNR therapy.

Additional information

Funding

This work was performed with financial support from the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology [2013 M2B2B1075774 and 2015 M2A2A7A1045270].