najoNanosystems: Physics, Chemistry, MathematicsНаносистемы: физика, химия, математика2220-80542305-7971Университет ИТМО10.17586/2220-8054-2020-11-3-324-332najo-429Research ArticleCHEMISTRY AND MATERIALS SCIENCEХИМИЯ И НАУКА О МАТЕРИАЛАХCeO2 nanoparticles as free radical regulators in biological systemsSozarukovaM. M.s_madinam@bk.ruProskurninaE. V.

Moskvorechie St, 1, Moscow, 115522

proskurnina@gmail.comBaranchikovA. E.a.baranchikov@yandex.ruIvanovV. K.van@igic.ras.ruKurnakov Institute of General and Inorganic Chemistry, Russian Academy of SciencesRussian FederationResearch Centre for Medical GeneticsRussian Federation202030072025113324–332Copyright © Sozarukova M.M., Proskurnina E.V., Baranchikov A.E., Ivanov V.K., 20252025Sozarukova M.M., Proskurnina E.V., Baranchikov A.E., Ivanov V.K.Sozarukova M.M., Proskurnina E.V., Baranchikov A.E., Ivanov V.K.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://nanojournal.ifmo.ru/jour/article/view/429

Cerium dioxide nanoparticles possess unique physical and chemical properties, among which the enzyme-like activity is of particular interest. In particular, they are able to perform the functions of pro- and antioxidant enzymes, such as superoxide dismutase (SOD), catalase, and peroxidase. Due to the advantages associated with pH and temperature stability and low cost, CeO2 nanoparticles can be considered as promising mimetics of these enzymes. In this paper, the antioxidant activity of a citrate-stabilized colloidal suspension of CeO2 nanoparticles has been studied using chemiluminometry in model systems generating superoxide anion radical and hydrogen peroxide. In the lucigenin/xanthine/xanthine oxidase system, generating a superoxide anion radical, CeO2 nanoparticles exhibit antioxidant properties increasing upon conjugation with SOD. When interacting with hydrogen peroxide, CeO2 nanoparticles exhibit peroxidase-like activity. In the combined ROS generating system, lucigenin/Co(II)/H2O2, CeO2 nanoparticles demonstrated prooxidant activity.

cerium dioxide nanoparticlessuperoxide anion radicalhydrogen peroxidenanozymessuperoxide dismutaseperoxidasechemiluminescenceThis work was supported by the Russian Science Foundation (project No. 19-13-00416).ReferencesYadav N., Patel V., Singh S. Cerium Oxide-Based Nanozymes in Biology and Medicine. Springer Proceedings in Physics, 2018, 236, P. 193– 213.Yadav N., Patel V., Singh S. Cerium Oxide-Based Nanozymes in Biology and Medicine. Springer Proceedings in Physics, 2018, 236, P. 193– 213.Gao L., Zhuang J., et al. Intrinsic peroxidase-like activity of ferromagnetic nanoparticles. Nat. Nanotechnol., 2007, 2 (9), P. 577–583.Gao L., Zhuang J., et al. Intrinsic peroxidase-like activity of ferromagnetic nanoparticles. Nat. Nanotechnol., 2007, 2 (9), P. 577–583.Chen T.M., Tian X.M., et al. Nanodiamonds as pH-switchable oxidation and reduction catalysts with enzyme-like activities for immunoassay and antioxidant applications. Nanoscale, 2017, 9 (40), P. 15673–15684.Chen T.M., Tian X.M., et al. Nanodiamonds as pH-switchable oxidation and reduction catalysts with enzyme-like activities for immunoassay and antioxidant applications. Nanoscale, 2017, 9 (40), P. 15673–15684.Cho S., Shin H.Y., Kim M.I. Nanohybrids consisting of magnetic nanoparticles and gold nanoclusters as effective peroxidase mimics and their application for colorimetric detection of glucose. Biointerphases, 2017, 12 (1), P. 01A401–01A407.Cho S., Shin H.Y., Kim M.I. Nanohybrids consisting of magnetic nanoparticles and gold nanoclusters as effective peroxidase mimics and their application for colorimetric detection of glucose. Biointerphases, 2017, 12 (1), P. 01A401–01A407.Vinothkumar G., Lalitha A.I., Suresh Babu K. Cerium Phosphate-Cerium Oxide Heterogeneous Composite Nanozymes with Enhanced Peroxidase-Like Biomimetic Activity for Glucose and Hydrogen Peroxide Sensing. Inorg. Chem., 2019, 58 (1), P. 349–358.Vinothkumar G., Lalitha A.I., Suresh Babu K. Cerium Phosphate-Cerium Oxide Heterogeneous Composite Nanozymes with Enhanced Peroxidase-Like Biomimetic Activity for Glucose and Hydrogen Peroxide Sensing. Inorg. Chem., 2019, 58 (1), P. 349–358.Naito Y., Yoshikawa T. Molecular and cellular mechanisms involved in Helicobacter pylori-induced inflammation and oxidative stress. Free Radic. Biol. Med., 2002, 33 (3), P. 323–336.Naito Y., Yoshikawa T. Molecular and cellular mechanisms involved in Helicobacter pylori-induced inflammation and oxidative stress. Free Radic. Biol. Med., 2002, 33 (3), P. 323–336.Sies H., Cadenas E. Oxidative stress: damage to intact cells and organs. Philos. Trans. R. Soc. Lond. B Biol. Sci., 1985, 311 (1152), P. 617–631.Sies H., Cadenas E. Oxidative stress: damage to intact cells and organs. Philos. Trans. R. Soc. Lond. B Biol. Sci., 1985, 311 (1152), P. 617–631.Yildirimer L., Thanh N.T., et al. Toxicology and clinical potential of nanoparticles. Nano Today, 2011, 6 (6), P. 585–607.Yildirimer L., Thanh N.T., et al. Toxicology and clinical potential of nanoparticles. Nano Today, 2011, 6 (6), P. 585–607.Ganguly R., Singh A.K., et al. Nanotechnology in Modern Animal Biotechnology. Elsevier, 2019, 178 p.Ganguly R., Singh A.K., et al. Nanotechnology in Modern Animal Biotechnology. Elsevier, 2019, 178 p.Ivanov V.K., Polezhaeva O.S., Tret’yakov Yu.D. Nanocrystalline ceria: Synthesis, structure-sensitive properties, and promising applications. Russ. J. Gen. Chem., 2010, 80, P. 604–617.Ivanov V.K., Polezhaeva O.S., Tret’yakov Yu.D. Nanocrystalline ceria: Synthesis, structure-sensitive properties, and promising applications. Russ. J. Gen. Chem., 2010, 80, P. 604–617.Grulke E., Reed K., et al. Nanoceria: factors affecting its pro- and anti-oxidant properties. Environ. Sci. Nano, 2014, 1, P. 429–444.Grulke E., Reed K., et al. Nanoceria: factors affecting its pro- and anti-oxidant properties. Environ. Sci. Nano, 2014, 1, P. 429–444.Popov A.L., Popova N.R., et al. Cerium oxide nanoparticles stimulate proliferation of primary mouse embryonic fibroblasts in vitro. Mater. Sci. Eng. C, 2016, 68, P. 406–413.Popov A.L., Popova N.R., et al. Cerium oxide nanoparticles stimulate proliferation of primary mouse embryonic fibroblasts in vitro. Mater. Sci. Eng. C, 2016, 68, P. 406–413.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.Shcherbakov A.B., Zholobak N.M., Spivak N.Ya., Ivanov V.K. Advances and prospects of using nanocrystalline ceria in cancer theranostics. Russ. J. Inorg. Chem., 2014, 59, P. 1556–1575.Shcherbakov A.B., Zholobak N.M., Spivak N.Ya., Ivanov V.K. Advances and prospects of using nanocrystalline ceria in cancer theranostics. Russ. J. Inorg. Chem., 2014, 59, P. 1556–1575.Shcherbakov A.B., Teplonogova M.A., et al. Facile method for fabrication of surfactant-free concentrated CeO2 sols. Mater. Res. Express, 2007, 4 (5), P. 4–14.Shcherbakov A.B., Teplonogova M.A., et al. Facile method for fabrication of surfactant-free concentrated CeO2 sols. Mater. Res. Express, 2007, 4 (5), P. 4–14.Gil D., Rodriguez J., et al. Antioxidant Activity of SOD and Catalase Conjugated with Nanocrystalline Ceria. Bioengineering, 2017, 4 (18), P. 1–9.Gil D., Rodriguez J., et al. Antioxidant Activity of SOD and Catalase Conjugated with Nanocrystalline Ceria. Bioengineering, 2017, 4 (18), P. 1–9.Li Y., He X., et al. Acquired superoxide-scavenging ability of ceria nanoparticles. Angew. Chem. Int. Ed. Engl., 2015, 54 (6), P. 1832–1835.Li Y., He X., et al. Acquired superoxide-scavenging ability of ceria nanoparticles. Angew. Chem. Int. Ed. Engl., 2015, 54 (6), P. 1832–1835.Kuppusamy P., Zweier J.L. Characterization of free radical generation by xanthine oxidase. Evidence for hydroxyl radical generation. J. Biol. Chem., 1989, 264 (17), P. 9880–9884.Kuppusamy P., Zweier J.L. Characterization of free radical generation by xanthine oxidase. Evidence for hydroxyl radical generation. J. Biol. Chem., 1989, 264 (17), P. 9880–9884.Phaniendra A., Jestadi D.B., Periyasamy L. Free radicals: properties, sources, targets, and their implication in various diseases. Indian J. Clin. Biochem., 2015, 30 (1), P. 11–26.Phaniendra A., Jestadi D.B., Periyasamy L. Free radicals: properties, sources, targets, and their implication in various diseases. Indian J. Clin. Biochem., 2015, 30 (1), P. 11–26.Kontos H.A., Wei E.P. et al. Appearance of superoxide anion radical in cerebral extracellular space during increased prostaglandin synthesis in cats. Circ. Res., 1985, 57 (1), P. 142–151.Kontos H.A., Wei E.P. et al. Appearance of superoxide anion radical in cerebral extracellular space during increased prostaglandin synthesis in cats. Circ. Res., 1985, 57 (1), P. 142–151.McIntyre M., Bohr D.F., Dominiczak A.F. Endothelial function in hypertension: the role of superoxide anion. Hypertension, 1999, 34 (4 Pt 1), P. 539–545.McIntyre M., Bohr D.F., Dominiczak A.F. Endothelial function in hypertension: the role of superoxide anion. Hypertension, 1999, 34 (4 Pt 1), P. 539–545.Babior B.M., Lambeth J.D., Nauseef W. The neutrophil NADPH oxidase. Arch. Biochem. Biophys., 2002, 397 (2), P. 342–344.Babior B.M., Lambeth J.D., Nauseef W. The neutrophil NADPH oxidase. Arch. Biochem. Biophys., 2002, 397 (2), P. 342–344.Kawano T., Kagenishi T., et al. Production and removal of superoxide anion radical by artificial metalloenzymes and redox-active metals. Commun. Integr. Biol., 2015, 8 (6), P. e1000710.Kawano T., Kagenishi T., et al. Production and removal of superoxide anion radical by artificial metalloenzymes and redox-active metals. Commun. Integr. Biol., 2015, 8 (6), P. e1000710.Lu J.M., Lin P.H., et al. Chemical and molecular mechanisms of antioxidants: experimental approaches and model systems. J. Cell. Mol. Med., 2010, 14 (4), P. 840–860.Lu J.M., Lin P.H., et al. Chemical and molecular mechanisms of antioxidants: experimental approaches and model systems. J. Cell. Mol. Med., 2010, 14 (4), P. 840–860.Perry J.J., Shin D.S., et al. The structural biochemistry of the superoxide dismutases. Biochim. Biophys. Acta, 2010, 1804 (2), P. 245–262.Perry J.J., Shin D.S., et al. The structural biochemistry of the superoxide dismutases. Biochim. Biophys. Acta, 2010, 1804 (2), P. 245–262.Tarnuzzer R.W., Colon J., et al. Vacancy engineered ceria nanostructures for protection from radiation-induced cellular damage. Nano Lett., 2005, 5 (12), P. 2573–2577.Tarnuzzer R.W., Colon J., et al. Vacancy engineered ceria nanostructures for protection from radiation-induced cellular damage. Nano Lett., 2005, 5 (12), P. 2573–2577.Korsvik C., Patil S., et al. Superoxide dismutase mimetic properties exhibited by vacancy engineered ceria nanoparticles. Chem. Commun. (Camb.), 2007, 10, P. 1056–1058.Korsvik C., Patil S., et al. Superoxide dismutase mimetic properties exhibited by vacancy engineered ceria nanoparticles. Chem. Commun. (Camb.), 2007, 10, P. 1056–1058.Heckert E.G., Karakoti A.S., et al. The role of cerium redox state in the SOD mimetic activity of nanoceria. Biomaterials, 2008, 29 (18), P. 2705–2709.Heckert E.G., Karakoti A.S., et al. The role of cerium redox state in the SOD mimetic activity of nanoceria. Biomaterials, 2008, 29 (18), P. 2705–2709.Karakoti A.S., Singh S., et al. PEGylated nanoceria as radical scavenger with tunable redox chemistry. J. Am. Chem. Soc., 2009, 131 (40), P. 14144–14145.Karakoti A.S., Singh S., et al. PEGylated nanoceria as radical scavenger with tunable redox chemistry. J. Am. Chem. Soc., 2009, 131 (40), P. 14144–14145.Singh V., Singh S., et al. A facile synthesis of PLGA encapsulated cerium oxide nanoparticles: release kinetics and biological activity. Nanoscale, 2012, 4 (8), P. 2597–2605.Singh V., Singh S., et al. A facile synthesis of PLGA encapsulated cerium oxide nanoparticles: release kinetics and biological activity. Nanoscale, 2012, 4 (8), P. 2597–2605.Jiao X., Song H., et al. Well-redispersed ceria nanoparticles: Promising peroxidase mimetics for H2O2 and glucose detection. Analytical Methods, 2012, 4, P. 3261–3267.Jiao X., Song H., et al. Well-redispersed ceria nanoparticles: Promising peroxidase mimetics for H2O2 and glucose detection. Analytical Methods, 2012, 4, P. 3261–3267.Xiaohua L., Zhang Zh., et al. A Chemiluminescence Microarray Based on Catalysis by CeO2 Nanoparticles and Its Application to Determine the Rate of Removal of Hydrogen Peroxide by Human Erythrocytes. Appl. Biochem. Biotechnol., 2013, 171 (1), P. 63–71.Xiaohua L., Zhang Zh., et al. A Chemiluminescence Microarray Based on Catalysis by CeO2 Nanoparticles and Its Application to Determine the Rate of Removal of Hydrogen Peroxide by Human Erythrocytes. Appl. Biochem. Biotechnol., 2013, 171 (1), P. 63–71.Lv C., Di W., et al. Luminescent CePO4:Tb colloids for H2O2 and glucose sensing. Analyst, 2014, 139 (18), P. 4547–4555.Lv C., Di W., et al. Luminescent CePO4:Tb colloids for H2O2 and glucose sensing. Analyst, 2014, 139 (18), P. 4547–4555.Tanaka S., Kaneti Y.V., et al. Mesoporous Iron Oxide Synthesized Using Poly(styrene-b-acrylic acid-b-ethylene glycol) Block Copolymer Micelles as Templates for Colorimetric and Electrochemical Detection of Glucose. ACS Appl. Mater. Interfaces, 2018, 10 (1), P. 1039–1049.Tanaka S., Kaneti Y.V., et al. Mesoporous Iron Oxide Synthesized Using Poly(styrene-b-acrylic acid-b-ethylene glycol) Block Copolymer Micelles as Templates for Colorimetric and Electrochemical Detection of Glucose. ACS Appl. Mater. Interfaces, 2018, 10 (1), P. 1039–1049.Shiralizadeh Dezfuli A., Ganjali M.R., Norouzi P. Facile sonochemical synthesis and morphology control of CePO(4) nanostructures via an oriented attachment mechanism: application as luminescent probe for selective sensing of Pb2+ ion in aqueous solution. Mater. Sci. Eng. C Mater. Biol. Appl., 2014, 42, P. 774–781.Shiralizadeh Dezfuli A., Ganjali M.R., Norouzi P. Facile sonochemical synthesis and morphology control of CePO(4) nanostructures via an oriented attachment mechanism: application as luminescent probe for selective sensing of Pb2+ ion in aqueous solution. Mater. Sci. Eng. C Mater. Biol. Appl., 2014, 42, P. 774–781.Han K.N., Choi J.S., Kwon J. Gold nanozyme-based paper chip for colorimetric detection of mercury ions. Sci. Rep., 2017, 7 (1), P. 1–7.Han K.N., Choi J.S., Kwon J. Gold nanozyme-based paper chip for colorimetric detection of mercury ions. Sci. Rep., 2017, 7 (1), P. 1–7.Bhattacharjee R., Tanaka S., et al. Porous Nanozymes: Peroxidase-Mimetic Activity of Mesoporous Iron Oxide for Calorimetric and Electrochemical Detection of Global DNA Methylation. J. Mater. Chem. B, 2018, 6, P. 4783–4791.Bhattacharjee R., Tanaka S., et al. Porous Nanozymes: Peroxidase-Mimetic Activity of Mesoporous Iron Oxide for Calorimetric and Electrochemical Detection of Global DNA Methylation. J. Mater. Chem. B, 2018, 6, P. 4783–4791.Maji S.K., Mandal A.K., et al. Cancer Cell Detection and Therapeutics Using Peroxidase-Active Nanohybrid of Gold Nanoparticle-Loaded Mesoporous Silica-Coated Graphene. ACS Appl. Mater. Interfaces, 2015, 7, P. 9807–9816.Maji S.K., Mandal A.K., et al. Cancer Cell Detection and Therapeutics Using Peroxidase-Active Nanohybrid of Gold Nanoparticle-Loaded Mesoporous Silica-Coated Graphene. ACS Appl. Mater. Interfaces, 2015, 7, P. 9807–9816.Ansari A.A., Solanki P.R., Malhotra B.D. Hydrogen peroxide sensor based on horseradish peroxidase immobilized nanostructured cerium oxide film. J. Biotechnol., 2009, 142 (2), P. 179–184.Ansari A.A., Solanki P.R., Malhotra B.D. Hydrogen peroxide sensor based on horseradish peroxidase immobilized nanostructured cerium oxide film. J. Biotechnol., 2009, 142 (2), P. 179–184.Zhidkova T.V., Proskurnina E.V., et al. Determination of superoxide dismutase and SOD-mimetic activities by a chemical system: Co2+/H2O2/lucigenin. Anal. Bioanal. Chem., 2011, 401 (1), P. 381–386.Zhidkova T.V., Proskurnina E.V., et al. Determination of superoxide dismutase and SOD-mimetic activities by a chemical system: Co2+/H2O2/lucigenin. Anal. Bioanal. Chem., 2011, 401 (1), P. 381–386.Iketani M., Ohsawa I. Molecular Hydrogen as a Neuroprotective Agent. Curr. Neuropharmacol., 2017, 15 (2), P. 324–331.Iketani M., Ohsawa I. Molecular Hydrogen as a Neuroprotective Agent. Curr. Neuropharmacol., 2017, 15 (2), P. 324–331.Xue Y., Luan Q., et al. Direct Evidence for Hydroxyl Radical Scavenging Activity of Cerium Oxide Nanoparticles. J. Phys. Chem., 2011, 115 (11), P. 4433–4438.Xue Y., Luan Q., et al. Direct Evidence for Hydroxyl Radical Scavenging Activity of Cerium Oxide Nanoparticles. J. Phys. Chem., 2011, 115 (11), P. 4433–4438.Schlick S., Danilczuk M., et al. Scavenging of Hydroxyl Radicals by Ceria Nanoparticles: Effect of Particle Size and Concentration. J. Phys. Chem. C, 2016, 120 (12), P. 6885–6890.Schlick S., Danilczuk M., et al. Scavenging of Hydroxyl Radicals by Ceria Nanoparticles: Effect of Particle Size and Concentration. J. Phys. Chem. C, 2016, 120 (12), P. 6885–6890.Popov A.L., Scherbakov A.B., et al. Cerium dioxide nanoparticles as third-generation enzymes (nanozymes). Nanosystems: Phys. Chem. Math., 2017, 8 (6), P. 760–781.Popov A.L., Scherbakov A.B., et al. Cerium dioxide nanoparticles as third-generation enzymes (nanozymes). Nanosystems: Phys. Chem. Math., 2017, 8 (6), P. 760–781.Linnane A.W., Kios M., Vitetta L. Healthy aging: regulation of the metabolome by cellular redox modulation and prooxidant signaling systems: the essential roles of superoxide anion and hydrogen peroxide. Biogerontology, 2007, 8 (5), P. 445–467.Linnane A.W., Kios M., Vitetta L. Healthy aging: regulation of the metabolome by cellular redox modulation and prooxidant signaling systems: the essential roles of superoxide anion and hydrogen peroxide. Biogerontology, 2007, 8 (5), P. 445–467.Spivak N.Y., Shepel E.A., et al. Ceria Nanoparticles Boost Activity of Aged Murine Oocytes. Nano Biomedicine and Engineering, 2012, 4, P. 188–194.Spivak N.Y., Shepel E.A., et al. Ceria Nanoparticles Boost Activity of Aged Murine Oocytes. Nano Biomedicine and Engineering, 2012, 4, P. 188–194.Courbiere B., Auffan M., et al. Ultrastructural interactions and genotoxicity assay of cerium dioxide nanoparticles on mouse oocytes. Int. J. Mol. Sci., 2013, 14 (11), P. 21613–21628.Courbiere B., Auffan M., et al. Ultrastructural interactions and genotoxicity assay of cerium dioxide nanoparticles on mouse oocytes. Int. J. Mol. Sci., 2013, 14 (11), P. 21613–21628.Smith R.A., Murphy M.P. Mitochondria-targeted antioxidants as therapies. Discov. Med., 2011, 11 (57), P. 106–114.Smith R.A., Murphy M.P. Mitochondria-targeted antioxidants as therapies. Discov. Med., 2011, 11 (57), P. 106–114.Liu Y., Shi J. Antioxidative nanomaterials and biomedical applications. Nano Today, 2019, 27, P. 146–177.Liu Y., Shi J. Antioxidative nanomaterials and biomedical applications. Nano Today, 2019, 27, P. 146–177.Jiang D., Ni D., et al. Nanozyme: new horizons for responsive biomedical applications. Chem. Soc. Rev., 2019, 48 (14), P. 3683–3704.Jiang D., Ni D., et al. Nanozyme: new horizons for responsive biomedical applications. Chem. Soc. Rev., 2019, 48 (14), P. 3683–3704.

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