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Quantitative Characterization of Free Radical Generation under Ir-192 Photon Irradiation for Gold Nanoparticle Mediated Radiation Therapy

Xie, Kanru
http://rave.ohiolink.edu/etdc/view?acc_num=mco1607005935210887

Abstract Details

2020, Master of Science in Biomedical Sciences (MSBS), University of Toledo, Biomedical Sciences (Medical Physics: Radiation Oncology).
In this study we investigate the primary mechanism responsible for the tumoricidal effect of high-energy photon irradiation in the presence of gold nanoparticles (GNP) in aqueous media. Multiple recent in vivo and in vitro studies demonstrated that the biological effect of cell irradiation is greatly enhanced in the presence of gold nanoparticles. The mechanism of the enhancement, however, is not very clear yet. Based on classical radiobiology, cell killing caused by ionizing radiation is due to DNA double strand breaks. For photons about two thirds are facilitated by water radiolysis creating reactive oxygen species (ROS), such as hydroxyl free radicals; another one third is from direct physical interactions of DNA molecule with radiation. As the physical dose enhancement due to presence of GNP in practically achievable concentrations is almost negligible under higher energy photon sources, we believe the effect is caused by an increase in generation of ROS at the GNP surface, acting as a catalyst. A novel approach to quantify the ROS generation through fluorescence spectroscopy is developed and validated in this study. Due to the short average life of ROS their detection requires use of chemical agents (“sensor”) capable of binding to ROS immediately upon their formation. Anthracene salt (anthracene-9,10-dipropionic acid disodium) is used as such fluorescent sensor molecule that selectively reacts with ROS. Samples of GNP solution and de-ionized (DI) water mixed with the sensor are irradiated under Ir-192 clinical high-dose rate (HDR) brachytherapy treatment source, having average photon energy of ~380keV. NaCl is added to samples after irradiation to segregate the nanoparticles and minimize their possible effect on the sample content after irradiation and before fluorescence analysis. The intensity of 430nm fluorescence spectroscopy peak is used to quantify the ROS generation. Our result shows that the radiation induced ROS generation could be doubled, reaching up to 110% enhancement, in presence of GNP. In parallel, we simulate the experimental setup using a Monte Carlo radiation transport package MCNP5 to evaluate the dose deposited from physical photon interaction processes. Proper geometries and materials of the experiment are modeled, in which GNP is created by repeated lattice structure method. Tracking the energy deposition in aqueous volume we found no difference beyond statistical uncertainty between GNP group and water only group. For practically achievable low GNP concentration levels increase in physical dose deposition plays almost no role at radiation therapy energy range, even for the lower photon energy range of the Ir-192 HDR source. We conclude from this study that free radical generation by water radiolysis can be quantitatively characterized by fluorescence spectroscopy. Cell killing enhancement in irradiated aqueous media due to the presence of GNP is vastly dominated by free radical production increase, mediating the biological response.
Diana Shvydka, PhD (Committee Chair)
E. Ishmael Parsai, PhD (Committee Member)
Nicholas Sperling, PhD (Committee Member)
93 p.
Health Sciences; Nanoscience; Physics; Radiation
gold nanoparticle, radiation therapy, free radical

Recommended Citations

Citations

  • Xie, K. (2020). Quantitative Characterization of Free Radical Generation under Ir-192 Photon Irradiation for Gold Nanoparticle Mediated Radiation Therapy [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1607005935210887

    APA Style (7th edition)

  • Xie, Kanru. Quantitative Characterization of Free Radical Generation under Ir-192 Photon Irradiation for Gold Nanoparticle Mediated Radiation Therapy. 2020. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1607005935210887.

    MLA Style (8th edition)

  • Xie, Kanru. "Quantitative Characterization of Free Radical Generation under Ir-192 Photon Irradiation for Gold Nanoparticle Mediated Radiation Therapy." Master's thesis, University of Toledo, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=mco1607005935210887

    Chicago Manual of Style (17th edition)

mco1607005935210887
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This open access ETD is published by University of Toledo Health Science Campus and OhioLINK.