X-ray activated nanoparticles destroy cancer in vitro........mouse models next. Researchers at Kyoto University, Japan have succeeded in destroying human ovarian cancer cells in vitro using silica nanoparticles containing iodine activated by specific wavelengths of X-rays. Instead of producing reactive oxygen species, activation involves the release of electrons that cause tumour DNA double strand breaks which induce apoptosis. The nanoparticles are preferentially taken up by the cancer cells.
"In addition, the nanoparticles have the potential to accumulate in the tumor due to passive as well as active mechanisms. Indeed, in vivo, the high vascularization and porosity of the blood vessel wall lead to preferential accumulation of nanoparticles in the tumor cells compared to healthy cells. This phenomenon, called Enhanced Permeability and Retention effect (EPR effect) has been widely used to target preferentially cancer cells and surface modification can also be performed as an active targeting strategy." Full paper available at:
Iodine containing porous organosilica nanoparticles trigger tumor spheroids destruction upon monochromatic X-ray irradiation: DNA breaks and K-edge energy X-ray
Open Access Published: 14 July 2021
Yuya Higashi, Kotaro Matsumoto, Hiroyuki Saitoh, Ayumi Shiro, Yue Ma, Mathilde Laird, Shanmugavel Chinnathambi, Albane Birault, Tan Le Hoang Doan, Ryo Yasuda, Toshiki Tajima, Tetsuya Kawachi & Fuyuhiko Tamanoi
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.