Yuya Higashi1, Kotaro Matsumoto1, Hiroyuki Saitoh2, Ayumi Shiro2, Yue Ma1, Mathilde Laird1, Shanmugavel Chinnathambi1, Albane Birault1, Tan Le Hoang Doan3, Ryo Yasuda2, Toshiki Tajima4, Tetsuya Kawachi2, Fuyuhiko Tamanoi5. 1. Institute for Integrated Cell-Material Sciences, Institute for Advanced Study, Kyoto University, Kyoto, Japan. 2. Kansai Photon Science Institute, Quantum Beam Science Research Directorate, National Institutes for Quantum and Radiological Science and Technology, Hyogo, Japan. 3. Center for Innovative Materials and Architectures, Vietnam National University-Ho Chi Minh City, Ho Chi Minh City, Vietnam. 4. Department of Physics and Astronomy, University of California, Irvine, CA, USA. 5. Institute for Integrated Cell-Material Sciences, Institute for Advanced Study, Kyoto University, Kyoto, Japan. tamanoi.fuyuhiko.2c@kyoto-u.ac.jp.
Abstract
X-ray irradiation of high Z elements causes photoelectric effects that include the release of Auger electrons that can induce localized DNA breaks. We have previously established a tumor spheroid-based assay that used gadolinium containing mesoporous silica nanoparticles and synchrotron-generated monochromatic X-rays. In this work, we focused on iodine and synthesized iodine-containing porous organosilica (IPO) nanoparticles. IPO were loaded onto tumor spheroids and the spheroids were irradiated with 33.2 keV monochromatic X-ray. After incubation in CO2 incubator, destruction of tumor spheroids was observed which was accompanied by apoptosis induction, as determined by the TUNEL assay. By employing the γH2AX assay, we detected double strand DNA cleavages immediately after the irradiation. These results suggest that IPO first generate double strand DNA breaks upon X-ray irradiation followed by apoptosis induction of cancer cells. Use of three different monochromatic X-rays having energy levels of 33.0, 33.2 and 33.4 keV as well as X-rays with 0.1 keV energy intervals showed that the optimum effect of all three events (spheroid destruction, apoptosis induction and generation of double strand DNA breaks) occurred with a 33.2 keV monochromatic X-ray. These results uncover the preferential effect of K-edge energy X-ray for tumor spheroid destruction mediated by iodine containing nanoparticles.
X-ray irradiation of high Z elements causes photoelectric effects that include the release of Auger electrons that can induce localized DNA breaks. We have previously establisn>an class="Chemical">hed a tumor spheroid-based assay that used gadolinium containing mesoporous silica nanoparticles and synchrotron-generated monochromatic X-rays. In this work, we focused on iodine and synthesized iodine-containing porous organosilica (IPO) nanoparticles. IPO were loaded onto tumor spheroids and the spheroids were irradiated with 33.2 keV monochromatic X-ray. After incubation in CO2 incubator, destruction of tumor spheroids was observed which was accompanied by apoptosis induction, as determined by the TUNEL assay. By employing the γH2AX assay, we detected double strand DNA cleavages immediately after the irradiation. These results suggest that IPO first generate double strand DNA breaks upon X-ray irradiation followed by apoptosis induction of cancer cells. Use of three different monochromatic X-rays having energy levels of 33.0, 33.2 and 33.4 keV as well as X-rays with 0.1 keV energy intervals showed that the optimum effect of all three events (spheroid destruction, apoptosis induction and generation of double strand DNA breaks) occurred with a 33.2 keV monochromatic X-ray. These results uncover the preferential effect of K-edge energy X-ray for tumor spheroid destruction mediated by iodine containing nanoparticles.
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