najoNanosystems: Physics, Chemistry, MathematicsНаносистемы: физика, химия, математика2220-80542305-7971Университет ИТМО10.17586/2220-8054-2019-10-5-564-572najo-1226Research ArticleCHEMISTRY AND MATERIALS SCIENCEХИМИЯ И НАУКА О МАТЕРИАЛАХCerium oxide nanoparticles provide radioprotective effects upon X-ray irradiation by modulation of gene expressionPopovaN. R.

Pushchino, Moscow region, 142290

nellipopovaran@gmail.comShekunovaT. O.

Moscow, 119991

taisia.shekunova@yandex.ruPopovA. L.

Pushchino, Moscow region, 142290

antonpopovleonid@gmail.comSeleznevaI. I.

Pushchino, Moscow region, 142290

selezneva_i@mail.ruIvanovV. K.

Moscow, 119991

van@igic.ras.ruInstitute of Theoretical and Experimental Biophysics, Russian Academy of SciencesRussian FederationKurnakov Institute of General and Inorganic Chemistry, Russian Academy of SciencesRussian Federation201923082025105564572Copyright © Popova N.R., Shekunova T.O., Popov A.L., Selezneva I.I., Ivanov V.K., 20252025Popova N.R., Shekunova T.O., Popov A.L., Selezneva I.I., Ivanov V.K.Popova N.R., Shekunova T.O., Popov A.L., Selezneva I.I., Ivanov V.K.This work is licensed under a Creative Commons Attribution 4.0 License.https://nanojournal.ifmo.ru/jour/article/view/1226

Nanocrystalline cerium dioxide is known as a unique redox active nanomaterial. Cerium dioxide is considered as the basis for future biomedical preparations, including radioprotectors. In the framework of this study, we synthesized citrate-stabilized CeO2 nanoparticles and carried out a comprehensive in vitro assessment of their radioprotective properties on a NCTC L929 murine fibroblast culture. It was shown that CeO2 nanoparticles ensure the survival of murine fibroblasts, even after high-dose X-ray irradiation, reducing the number of dead cells in the culture and modulating the mRNA level of the key antioxidant enzymes – superoxide dismutase 1 (SOD1) and superoxide dismutase 2 (SOD2). The results obtained confirm the potential for studying the properties of CeO2 nanoparticles as basic materials for designing new efficient and safe preparations for protection against ionizing radiation.

cerium oxide nanoparticlesradioprotectioncytotoxicityX-rayionizing radiationfibroblastsReferencesYounis A., Chu D., Li S. Cerium Oxide Nanostructures and their Applications. Intech. Open, 2016, 3, P. 53–68.Younis A., Chu D., Li S. Cerium Oxide Nanostructures and their Applications. Intech. Open, 2016, 3, P. 53–68.Shcherbakov A.B., Zholobak N., Ivanov V.K. Biological, biomedical and pharmaceutical applications of cerium oxide. In: Metal Oxides Series: Cerium Oxide (CeO2): Synthesis, Properties and Applications. Publisher: Elsevier, Amsterdam, 2019, P. 279–358.Shcherbakov A.B., Zholobak N., Ivanov V.K. Biological, biomedical and pharmaceutical applications of cerium oxide. In: Metal Oxides Series: Cerium Oxide (CeO2): Synthesis, Properties and Applications. Publisher: Elsevier, Amsterdam, 2019, P. 279–358.Zholobak N.M., Ivanov V.K., et al. UV-shielding property, photocatalytic activity and photocytotoxicity of ceria colloid solutions. J. Photochem. Photobiolog. B: Biology, 2011, 102, P. 32–38.Zholobak N.M., Ivanov V.K., et al. UV-shielding property, photocatalytic activity and photocytotoxicity of ceria colloid solutions. J. Photochem. Photobiolog. B: Biology, 2011, 102, P. 32–38.Popov A.L., Shcherbakov A.B., et al. Cerium dioxide nanoparticles as third-generation enzymes (Nanozymes). Nanosystems: Physics, Chemistry, Mathematics, 2017, 8 (6), P. 760–781.Popov A.L., Shcherbakov A.B., et al. Cerium dioxide nanoparticles as third-generation enzymes (Nanozymes). Nanosystems: Physics, Chemistry, Mathematics, 2017, 8 (6), P. 760–781.Popov A.L., Zaichkina S.I., et al. Radioprotective effects of ultra-small citrate-stabilized cerium oxide nanoparticles in vitro and in vivo. RSC Adv., 2016, 6, P. 106141–106149.Popov A.L., Zaichkina S.I., et al. Radioprotective effects of ultra-small citrate-stabilized cerium oxide nanoparticles in vitro and in vivo. RSC Adv., 2016, 6, P. 106141–106149.Caputo F., Giovannetti A., et al. Cerium oxide nanoparticles re-establish cell integrity checkpoints and apoptosis competence in irradiated HaCat cells via novel redox-independent activity. Front Pharmacol., 2018, 9, 1183.Caputo F., Giovannetti A., et al. Cerium oxide nanoparticles re-establish cell integrity checkpoints and apoptosis competence in irradiated HaCat cells via novel redox-independent activity. Front Pharmacol., 2018, 9, 1183.Wason M.S., Lu H., et al. Cerium oxide nanoparticles sensitize pancreatic cancer to radiation therapy through oxidative activation of the JNK apoptotic pathway. Cancers (Basel), 2018, 10 (9), 303.Wason M.S., Lu H., et al. Cerium oxide nanoparticles sensitize pancreatic cancer to radiation therapy through oxidative activation of the JNK apoptotic pathway. Cancers (Basel), 2018, 10 (9), 303.Xu P-T., Maidment B.W., et al. Cerium oxide nanoparticles: A potential medical countermeasure to mitigate radiation-induced lung injury in CBA/J Mice. Radiat. Res., 2016, 185, P. 516–526.Xu P-T., Maidment B.W., et al. Cerium oxide nanoparticles: A potential medical countermeasure to mitigate radiation-induced lung injury in CBA/J Mice. Radiat. Res., 2016, 185, P. 516–526.Zal Z., Ghasemi A., et al. Radioprotective effect of cerium oxide nanoparticles against genotoxicity induced by ionizing radiation on human lymphocytes. Curr. Radiopharm., 2018, 11 (2), P. 109–115.Zal Z., Ghasemi A., et al. Radioprotective effect of cerium oxide nanoparticles against genotoxicity induced by ionizing radiation on human lymphocytes. Curr. Radiopharm., 2018, 11 (2), P. 109–115.Colon J., Herrera L., et al. Protection from radiation-induced pneumonitis using cerium oxide nanoparticles. Nanomedicine, 2009, 5 (2), P. 225–231.Colon J., Herrera L., et al. Protection from radiation-induced pneumonitis using cerium oxide nanoparticles. Nanomedicine, 2009, 5 (2), P. 225–231.Colon J., Hsieh N., et al. Cerium oxide nanoparticles protect gastrointestinal epithelium from radiation-induced damage by reduction of reactive oxygen species and upregulation of superoxide dismutase 2. Nanomedicine, 2010, 6 (5), P. 698–705.Colon J., Hsieh N., et al. Cerium oxide nanoparticles protect gastrointestinal epithelium from radiation-induced damage by reduction of reactive oxygen species and upregulation of superoxide dismutase 2. Nanomedicine, 2010, 6 (5), P. 698–705.Madero-Visbal R.A., Alvarado B.E., et al. Harnessing nanoparticles to improve toxicity after head and neck radiation. Nanomedicine, 2012, 8 (7), P. 1223–1231.Madero-Visbal R.A., Alvarado B.E., et al. Harnessing nanoparticles to improve toxicity after head and neck radiation. Nanomedicine, 2012, 8 (7), P. 1223–1231.Tarnuzzer R.W., Colon J., Patil S., Seal S. Vacancy engineered ceria nanostructures for protection from radiation-induced cellular damage. Nano Lett., 2005, 5 (12), P. 2573–2577.Tarnuzzer R.W., Colon J., Patil S., Seal S. Vacancy engineered ceria nanostructures for protection from radiation-induced cellular damage. Nano Lett., 2005, 5 (12), P. 2573–2577.Briggs A., Corde S., et al. Cerium oxide nanoparticles: influence of the high-Z component revealed on radioresistant 9L cell survival under X-ray irradiation. Nanomedicine, 2013, 9 (7), P. 1098–1105.Briggs A., Corde S., et al. Cerium oxide nanoparticles: influence of the high-Z component revealed on radioresistant 9L cell survival under X-ray irradiation. Nanomedicine, 2013, 9 (7), P. 1098–1105.Ivanov V.K., Polezhaeva O.S., et al. Synthesis and thermal stability of nanocrystalline ceria sols stabilized by citric and polyacrylic acids. Russ. J. Inorg. Chem., 2010, 55 (3), P. 328–332.Ivanov V.K., Polezhaeva O.S., et al. Synthesis and thermal stability of nanocrystalline ceria sols stabilized by citric and polyacrylic acids. Russ. J. Inorg. Chem., 2010, 55 (3), P. 328–332.Zholobak N.M., Shcherbakov A.B., et al. Panthenol-stabilized cerium dioxide nanoparticles for cosmeceutic formulations against ROSinduced and UV-induced damage. J. Photochem. Photobiol. B, 2014, 130, P. 102–108.Zholobak N.M., Shcherbakov A.B., et al. Panthenol-stabilized cerium dioxide nanoparticles for cosmeceutic formulations against ROSinduced and UV-induced damage. J. Photochem. Photobiol. B, 2014, 130, P. 102–108.Ivanova O.S., Shekunova T.O., et al. One-stage synthesis of ceria colloid solutions for biomedical use. Dokl. Chem., 2011, 437 (2), P. 103–106.Ivanova O.S., Shekunova T.O., et al. One-stage synthesis of ceria colloid solutions for biomedical use. Dokl. Chem., 2011, 437 (2), P. 103–106.Stoianov O.O., Ivanov V.K., et al. Determination of cerium(III) and cerium(IV) in nanodisperse ceria by chemical methods. Russ. J. Inorg. Chem., 2014, 59 (2), P. 15–23.Stoianov O.O., Ivanov V.K., et al. Determination of cerium(III) and cerium(IV) in nanodisperse ceria by chemical methods. Russ. J. Inorg. Chem., 2014, 59 (2), P. 15–23.Maksimchuk P.O., Masalov A.A., Malyukin Yu.V. Spectroscopically detected formation of oxygen vacancies in nanocrystalline CeO2x. Journal of nano- and electronic physics, 2013, 5 (1), 01004.Maksimchuk P.O., Masalov A.A., Malyukin Yu.V. Spectroscopically detected formation of oxygen vacancies in nanocrystalline CeO2x. Journal of nano- and electronic physics, 2013, 5 (1), 01004.Maksimchuk P., Masalov A.A. Optically detected effect of size on the oxygen vacancies concentration in cerium oxide nanocrystals. Proceedings of the International Conference Nanomaterials: Applications and Properties, Alushta, 2014, 3 (2), 02NAESF05.Maksimchuk P., Masalov A.A. Optically detected effect of size on the oxygen vacancies concentration in cerium oxide nanocrystals. Proceedings of the International Conference Nanomaterials: Applications and Properties, Alushta, 2014, 3 (2), 02NAESF05.Le Caër S. Water Radiolysis: Influence of Oxide Surfaces on H2 Production under Ionizing Radiation. Water, 2011, 3, P. 235–253.Le Caër S. Water Radiolysis: Influence of Oxide Surfaces on H2 Production under Ionizing Radiation. Water, 2011, 3, P. 235–253.Espinosa-Diez C., Miguel V., et al. Antioxidant responses and cellular adjustments to oxidative stress. Redox Biol., 2015, 6, P. 183–197.Espinosa-Diez C., Miguel V., et al. Antioxidant responses and cellular adjustments to oxidative stress. Redox Biol., 2015, 6, P. 183–197.Zhao Y., Seefeldt T., et al. Effects of glutathione reductase inhibition on cellular thiol redox state and related systems. Arch. Biochem. Biophys., 2009, 485 (1), P. 56–62.Zhao Y., Seefeldt T., et al. Effects of glutathione reductase inhibition on cellular thiol redox state and related systems. Arch. Biochem. Biophys., 2009, 485 (1), P. 56–62.Couto N.,Wood J., Barber J. The role of glutathione reductase and related enzymes on cellular redox homoeostasis network. Free Radic. Biol. Med., 2016, 95, P. 27–42.Couto N.,Wood J., Barber J. The role of glutathione reductase and related enzymes on cellular redox homoeostasis network. Free Radic. Biol. Med., 2016, 95, P. 27–42.Murley J.S., Kataoka Y., et al. Delayed cytoprotection after enhancement of SOD2 (MnSOD) gene expression in SA-NH mouse sarcoma cells exposed to WR-1065, the active metabolite of amifostine. Radiat. Res., 2002, 158, P. 101–109.Murley J.S., Kataoka Y., et al. Delayed cytoprotection after enhancement of SOD2 (MnSOD) gene expression in SA-NH mouse sarcoma cells exposed to WR-1065, the active metabolite of amifostine. Radiat. Res., 2002, 158, P. 101–109.Wong G.H. Protective roles of cytokines against radiation: induction of mitochondrial MnSOD. Biochim. Biophys. Acta, 1995, 1271, P. 205– 209.Wong G.H. Protective roles of cytokines against radiation: induction of mitochondrial MnSOD. Biochim. Biophys. Acta, 1995, 1271, P. 205– 209.Hirose K., Longo D.L., Oppenheim J.J., Matsushima K. Overexpression of mitochondrial manganese superoxide dismutase promotes the survival of tumor cells exposed to interlukin-1, tumor necrosis factor, selected anticancer drugs, and ionizing radiation. FASEB J., 1993, 7, P. 361–368.Hirose K., Longo D.L., Oppenheim J.J., Matsushima K. Overexpression of mitochondrial manganese superoxide dismutase promotes the survival of tumor cells exposed to interlukin-1, tumor necrosis factor, selected anticancer drugs, and ionizing radiation. FASEB J., 1993, 7, P. 361–368.Sun J., Chen Y., Li M., Ge Z. Role of antioxidant enzymes on ionizing radiation resistance. Free Radic. Biol. Med., 1998, 24, P. 586–593.Sun J., Chen Y., Li M., Ge Z. Role of antioxidant enzymes on ionizing radiation resistance. Free Radic. Biol. Med., 1998, 24, P. 586–593.Motoori S., Majima H.J., et al. Overexpression of mitochondrial manganese superoxide dismutase protects against radiation-induced cell death in the human hepatocellular carcinoma cell. Cancer Research, 2001, 61, P. 5382–5388.Motoori S., Majima H.J., et al. Overexpression of mitochondrial manganese superoxide dismutase protects against radiation-induced cell death in the human hepatocellular carcinoma cell. Cancer Research, 2001, 61, P. 5382–5388.Selvaraj V., Nepal N., et al. Inhibition of MAP kinase/NF-kB mediated signaling and attenuation of lipopolysaccharide induced severe sepsis by cerium oxide nanoparticles. Biomaterials, 2015, 59, P. 160–171.Selvaraj V., Nepal N., et al. Inhibition of MAP kinase/NF-kB mediated signaling and attenuation of lipopolysaccharide induced severe sepsis by cerium oxide nanoparticles. Biomaterials, 2015, 59, P. 160–171.

The authors declare that there are no conflicts of interest present.