najoNanosystems: Physics, Chemistry, MathematicsНаносистемы: физика, химия, математика2220-80542305-7971Университет ИТМО10.17586/2220-8054-2022-13-3-308-313najo-242Research ArticleСтатьиCeO2-calcein nanoconjugate protective action against H2O2-induced oxidative stress in vitroChukavinN. N.chukavinnik@gmail.comPopovA. L.antonpopovleonid@gmail.comShcherbakovA. B.ceroform@gmail.comIvanovaO. S.runetta05@mail.ruFilippovaA. D.IvanovV. K.van@igic.ras.ruInstitute of Theoretical and Experimental Biophysics; Moscow Region State UniversityRussian FederationInstitute of Theoretical and Experimental BiophysicsRussian FederationZabolotny Institute of Microbiology and VirologyRussian FederationKurnakov Institute of General and Inorganic ChemistryRussian Federation202206062025133308313Copyright © Chukavin N.N., Popov A.L., Shcherbakov A.B., Ivanova O.S., Filippova A.D., Ivanov V.K., 20252025Chukavin N.N., Popov A.L., Shcherbakov A.B., Ivanova O.S., Filippova A.D., Ivanov V.K.Chukavin N.N., Popov A.L., Shcherbakov A.B., Ivanova O.S., Filippova A.D., 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/242

We studied cerium oxide-calcein nanoconjugate, which is capable of providing intracellular detection and simultaneous inactivation of reactive oxygen species (ROS). The synthesized nanoconjugate is easily uptaken by human mesenchymal stem cells (MSCs) and demonstrates antioxidant properties, protecting cells from H2O2-induced oxidative stress in vitro. Cerium oxide-calcein nanoconjugate neutralizes hydrogen peroxide, meanwhile releasing brightly fluorescent calcein from its surface, which is easily detected by fluorimeter or fluorescent microscope. This nanoconjugate is biocompatible and non-toxic to MSCs in concentrations below 2 mM. Such a theranostic agent can be considered as a promising tool for tracking the redox status of human MSCs in vivo.

cerium oxidecalceinbioimagingcell uptakeoxidative stresstheranosticsReferencesShcherbakov A.B., Reukov V., et al. CeO2 nanoparticle-containing polymers for biomedical applications: A review. Polymers, 2021, 13 (6), 924.Shcherbakov A.B., Reukov V., et al. CeO2 nanoparticle-containing polymers for biomedical applications: A review. Polymers, 2021, 13 (6), 924.Dhall A., Self W. Cerium Oxide Nanoparticles: A Brief Review of Their Synthesis Methods and Biomedical Applications. Antioxidants, 2018, 7 (8), 97.Dhall A., Self W. Cerium Oxide Nanoparticles: A Brief Review of Their Synthesis Methods and Biomedical Applications. Antioxidants, 2018, 7 (8), 97.Rajeshkumar S., Naik P. Synthesis and biomedical applications of Cerium oxide nanoparticles - A Review. Biotechnol. Rep. (Amst), 2017, 17, P. 1-5.Rajeshkumar S., Naik P. Synthesis and biomedical applications of Cerium oxide nanoparticles - A Review. Biotechnol. Rep. (Amst), 2017, 17, P. 1-5.Lord M.S., Berret J.F., et al. Redox Active Cerium Oxide Nanoparticles: Current Status and Burning Issues. Small, 2021, 17 (51), e2102342.Lord M.S., Berret J.F., et al. Redox Active Cerium Oxide Nanoparticles: Current Status and Burning Issues. Small, 2021, 17 (51), e2102342.Chai W.F., Tang K.S. Protective potential of cerium oxide nanoparticles in diabetes mellitus. J. Trace Elem. Med. Biol., 2021, 66, 126742.Chai W.F., Tang K.S. Protective potential of cerium oxide nanoparticles in diabetes mellitus. J. Trace Elem. Med. Biol., 2021, 66, 126742.Gao Y., Chen K., Ma J.L., Gao F. Cerium oxide nanoparticles in cancer. Onco Targets Ther., 2014, 7, P. 835-840.Gao Y., Chen K., Ma J.L., Gao F. Cerium oxide nanoparticles in cancer. Onco Targets Ther., 2014, 7, P. 835-840.Hu X., Zhao P., Lu Y., Liu Y. ROS-Based Nanoparticles for Atherosclerosis Treatment. Materials, 2021, 14 (22), 6921.Hu X., Zhao P., Lu Y., Liu Y. ROS-Based Nanoparticles for Atherosclerosis Treatment. Materials, 2021, 14 (22), 6921.Pirmohamed T., Dowding J.M., et al. Nanoceria exhibit redox state-dependent catalase mimetic activity. Chem.Commun., 2010, 46 (16), P. 2736-2738.Pirmohamed T., Dowding J.M., et al. Nanoceria exhibit redox state-dependent catalase mimetic activity. Chem.Commun., 2010, 46 (16), P. 2736-2738.Heckert E.G., Karakoti A.S., Seal S., Self W.T. 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., Seal S., Self W.T. The role of cerium redox state in the SOD mimetic activity of nanoceria. Biomaterials, 2008, 29 (18), P. 2705-2709.Asati A., Santra S., et al. Oxidase-like activity of polymer-coated cerium oxide nanoparticles. Angew Chem.Int. Ed. Engl., 2009, 48 (13), P. 2308-2312.Asati A., Santra S., et al. Oxidase-like activity of polymer-coated cerium oxide nanoparticles. Angew Chem.Int. Ed. Engl., 2009, 48 (13), P. 2308-2312.Xu C., Qu X. Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Mater., 2014, 6, e90.Xu C., Qu X. Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Mater., 2014, 6, e90.Dhall A., Burns A., et al. Characterizing the phosphatase mimetic activity of cerium oxide nanoparticles and distinguishing its active site from that for catalase mimetic activity using anionic inhibitors Environ. Sci.: Nano, 2017, 4, P. 1742-1749.Dhall A., Burns A., et al. Characterizing the phosphatase mimetic activity of cerium oxide nanoparticles and distinguishing its active site from that for catalase mimetic activity using anionic inhibitors Environ. Sci.: Nano, 2017, 4, P. 1742-1749.Dar M.A., Gul R., et al. Size-Dependent Effect of Nanoceria on Their Antibacterial Activity Towards Escherichia coli. Science of Advanced Materials, 2017, 9 (7), P. 1248-1253.Dar M.A., Gul R., et al. Size-Dependent Effect of Nanoceria on Their Antibacterial Activity Towards Escherichia coli. Science of Advanced Materials, 2017, 9 (7), P. 1248-1253.Alpaslan E., Yazici H., et al. pH-Dependent Activity of Dextran-Coated Cerium Oxide Nanoparticles on Pr ohibiting Osteosarcoma Cell Proliferation. ACS Biomater. Sci. Eng., 2015, 1 (11), P. 1096-1103.Alpaslan E., Yazici H., et al. pH-Dependent Activity of Dextran-Coated Cerium Oxide Nanoparticles on Pr ohibiting Osteosarcoma Cell Proliferation. ACS Biomater. Sci. Eng., 2015, 1 (11), P. 1096-1103.Popov A., Abakumov M., et al. Biocompatible dextran-coated gadolinium-doped cerium oxide nanoparticles as MRI contrast agents with high T1 relaxivity and selective cytotoxicity to cancer cells. J. Mater. Chem. B, 2021, 9, P. 6586-6599.Popov A., Abakumov M., et al. Biocompatible dextran-coated gadolinium-doped cerium oxide nanoparticles as MRI contrast agents with high T1 relaxivity and selective cytotoxicity to cancer cells. J. Mater. Chem. B, 2021, 9, P. 6586-6599.Kalashnikova I., Chung S.J., et al. Ceria-based nanotheranostic agent for rheumatoid arthritis. Theranostics, 2020, 10 (26), P. 11863-11880.Kalashnikova I., Chung S.J., et al. Ceria-based nanotheranostic agent for rheumatoid arthritis. Theranostics, 2020, 10 (26), P. 11863-11880.Zholobak N.M., Shcherbakov A.B., et al. Direct monitoring of the interaction between ROS and cerium dioxide nanoparticles in living cells. RSC Adv., 2014, 4, P. 51703-51710.Zholobak N.M., Shcherbakov A.B., et al. Direct monitoring of the interaction between ROS and cerium dioxide nanoparticles in living cells. RSC Adv., 2014, 4, P. 51703-51710.Popov A.L., Zaichkina S.I., et al. Radioprotective effects of ultra-small citrate-stabilized cerium oxide nanoparticles. RSC Advances, 2016, 6, P. 106141-106149.Popov A.L., Zaichkina S.I., et al. Radioprotective effects of ultra-small citrate-stabilized cerium oxide nanoparticles. RSC Advances, 2016, 6, P. 106141-106149.Xiang J., Li J., et al. Cerium Oxide Nanoparticle Modi ed Scaffold Interface Enhances Vascularization of Bone Grafts by Activating Calcium Channel of Mesenchymal Stem Cells. ACS Appl. Mater.Interfaces, 2016, 8 (7), P. 4489-4499.Xiang J., Li J., et al. Cerium Oxide Nanoparticle Modi ed Scaffold Interface Enhances Vascularization of Bone Grafts by Activating Calcium Channel of Mesenchymal Stem Cells. ACS Appl. Mater.Interfaces, 2016, 8 (7), P. 4489-4499.Zuo L., Feng Q., et al. Therapeutic effect on experimental acute cerebral infarction is enhanced after nanoceria labeling of human umbilical cord mesenchymal stem cells. Ther. Adv. Neurol. Disord, 2019, 12, 1756286419859725.Zuo L., Feng Q., et al. Therapeutic effect on experimental acute cerebral infarction is enhanced after nanoceria labeling of human umbilical cord mesenchymal stem cells. Ther. Adv. Neurol. Disord, 2019, 12, 1756286419859725.Hollo´ Z., Homolya L., Davis C.W., Sarkadi B. Calcein accumulation as a uorometric functional assay of the multidrug transporter. Biochim. Biophys. Acta, 1994, 1191 (2), P. 384-388.Hollo´ Z., Homolya L., Davis C.W., Sarkadi B. Calcein accumulation as a uorometric functional assay of the multidrug transporter. Biochim. Biophys. Acta, 1994, 1191 (2), P. 384-388.Whittemore E.R., Loo D.T., Watt J.A., Cotman C.W. A detailed analysis of hydrogen peroxide-induced cell death in primary neuronal culture. Neuroscience, 1995, 67 (4), P. 921-932.Whittemore E.R., Loo D.T., Watt J.A., Cotman C.W. A detailed analysis of hydrogen peroxide-induced cell death in primary neuronal culture. Neuroscience, 1995, 67 (4), P. 921-932.Fang X., Zhang X., Li H. Oxidative stress and mitochondrial membrane potential are involved in the cytotoxicity of per uorododecanoic acid to neurons. Toxicol. Ind. Health, 2020, 36 (11), P. 892-897.Fang X., Zhang X., Li H. Oxidative stress and mitochondrial membrane potential are involved in the cytotoxicity of per uorododecanoic acid to neurons. Toxicol. Ind. Health, 2020, 36 (11), P. 892-897.

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