vestnik-bio-msuВестник Московского университета. Серия 16. БиологияVestnik Moskovskogo universiteta. Seriya 16. Biologiya0137-0952Lomonosov Moscow State University, School of Biology10.55959/MSU0137-0952-16-78-4-8vestnik-bio-msu-1244Research ArticleОРИГИНАЛЬНОЕ ИССЛЕДОВАНИЕRESEARCH ARTICLEОлигорибонуклеотид-содержащие нанокомплексы на основе наночастиц аминопропилсиланола как эффективные ингибиторы репликации вируса гриппа АOligoribonucleotide-containing nanocomplexes based on aminopropylsilanol nanoparticles as effective inhibitors of influenza A virus replicationhttps://orcid.org/0000-0002-7108-9036РепковаМ. Н.RepkovaM. N.

Репкова Марина Николаевна – канд. хим. наук, науч. сотр. ИХБФМ СО РАН

Institute of Chemical Biology and Fundamental Medicine, Siberian Brunch of Russian Academy of Sciences

repk56@mail.ruhttps://orcid.org/0000-0001-8164-4091МазурковО. Ю.MazurkovO. Yu.

Мазурков Олег Юрьевич – канд. биол. наук, науч. сотр. ГНЦ ВБ «Вектор»

mazurkov_oleg@mail.ruhttps://orcid.org/0000-0001-9554-4462ФилипповаЕ. И.FilippovaE. I.

Филиппова Екатерина Игоревна – канд. биол. наук, науч. сотр. ГНЦ ВБ «Вектор»

filippova.ekaterina.89@gmail.comПроценкоМ. А.ProcenkoM. A.

Проценко Мария Анатольевна – канд. биол. наук, ст. науч. сотр. ГНЦ ВБ «Вектор»

mpbioteh@mail.ruhttps://orcid.org/0000-0002-1896-2684МазурковаН. А.MazurkovaN. A.

Мазуркова Наталья Алексеевна – докт. биол. наук, зав. лаб. ГНЦ ВБ «Вектор»

mazurkova@vector.nsc.ruhttps://orcid.org/0000-0002-2958-2580ЧелобановБ. П.ChelobanovB. P.

Челобанов Борис Павлович – канд. биол. наук, ст. науч. сотр. ИХБФМ СО РАН

Institute of Chemical Biology and Fundamental Medicine, Siberian Brunch of Russian Academy of Sciences

boris.p.chelobanov@gmail.comhttps://orcid.org/0000-0003-2423-3805ЛевинаА. С.LevinaA. S.

Левина Ася Сауловна – канд. хим. наук, ст. науч. сотр. ИХБФМ СО РАН

Institute of Chemical Biology and Fundamental Medicine, Siberian Brunch of Russian Academy of Sciences

asl1032@yandex.ruhttps://orcid.org/0000-0002-9579-9972ЗарытоваВ. Ф.ZarytovaV. F.

Левина Ася Сауловна – канд. хим. наук, ст. науч. сотр. ИХБФМ СО РАН

 

Institute of Chemical Biology and Fundamental Medicine, Siberian Brunch of Russian Academy of Sciences

zarytova@niboch.nsc.ruИнститут химической биологии и фундаментальной медициныРоссияInstitute of Chemical Biology and Fundamental MedicineRussian FederationГосударственный научный центр вирусологии и биотехнологии «Вектор»РоссияState Research Center of Virology and Biotechnology “Vector”Russian Federation202327022024784267272Copyright © Репкова М.Н., Мазурков О.Ю., Филиппова Е.И., Проценко М.А., Мазуркова Н.А., Челобанов Б.П., Левина А.С., Зарытова В.Ф., 20232023Репкова М.Н., Мазурков О.Ю., Филиппова Е.И., Проценко М.А., Мазуркова Н.А., Челобанов Б.П., Левина А.С., Зарытова В.Ф.Repkova M.N., Mazurkov O.Y., Filippova E.I., Procenko M.A., Mazurkova N.A., Chelobanov B.P., Levina A.S., Zarytova V.F.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestnik-bio-msu.elpub.ru/jour/article/view/1244

Наночастицы диоксида титана или аминопропилсиланола являются эффективными средствами доставки олигодезоксирибонуклеотидов и дезоксирибозимов в клетки с целью их воздействия на нуклеиновые кислоты-мишени. В данной работе предложенный принцип доставки осуществлен в отношении олигорибонуклеотидов (ORN). Показано, что полученные ORN-содержащие нанокомплексы (Si~NH2▪ORN) на основе наночастиц аминопропилсиланола (Si~NH2) проникают в эукариотические клетки. Эти нанокомплексы исследованы в качестве агентов для подавления репликации вируса гриппа А в клеточной системе. Показано, что ORN в составе нанокомплекса, направленные на (+)РНК и (–)РНК 5-го сегмента вируса гриппа А, понижают титр вируса соответственно на 99,7% и 98,4%. Таким образом, олигорибонуклеотиды в составе нанокомплексов (Si~NH2▪ORN) эффективно ингибируют репликацию вируса гриппа А.

Titanium dioxide or aminopropylsilanol nanoparticles were shown to be effective vehicles for delivering oligodeoxyribonucleotides and deoxyribozymes to cells to affect target nucleic acids. In this paper, the proposed principle of the delivery has been implemented in relation to oligoribonucleotides (ORN), components of short interfering RNAs (siRNAs). It has been shown that the obtained ORN-containing nanocomplexes (Si~NH2▪ORN) based on aminopropylsilanol nanoparticles penetrate eukaryotic cells. These nanocomplexes have been investigated as agents for suppressing the replication of influenza A virus (IAV) in the cellular system. It has been shown that the ORN strands targeted to (+)RNA and (–)RNA of the IAV 5th segment reduces the titer of the virus by 99.7% and 98.4%, respectively. Thus, oligoribonucleotides in the Si~NH2▪ORN nanocomplexes effectively inhibit the replication of the influenza A virus.

олигорибонуклеотидынаночастицы аминопропилсиланолананокомплексыдоставка в клеткивирус гриппа Апротивовирусная активностьoligoribonucleotidesaminopropylsilanol nanoparticlesnanocomplexescell deliveryinfluenza A virusantiviral activityИсследование выполнено при финансовой поддержке Российского научного фонда (проект № 23-25-00230)The research was funded by Russian Foundation for Basic Research, project number 23-25-00230ReferencesChernikov I.V., Vlassov V.V., Chernolovskaya E.L. Current development of siRNA bioconjugates: from research to the clinic. Front. Pharmacol. 2019;10:444.Chernikov I.V., Vlassov V.V., Chernolovskaya E.L. Current development of siRNA bioconjugates: from research to the clinic. Front. Pharmacol. 2019;10:444.Fabrega C., Aviñó A., Navarro N., Jorge A.F., Grijalvo S., Eritja R. Lipid and peptide-oligonucleotide conjugates for therapeutic purposes: from simple hybrids to complex multifunctional assemblies. Pharmaceutics 2023;15(2):320.Fabrega C., Aviñó A., Navarro N., Jorge A.F., Grijalvo S., Eritja R. Lipid and peptide-oligonucleotide conjugates for therapeutic purposes: from simple hybrids to complex multifunctional assemblies. Pharmaceutics 2023;15(2):320.Lim S.A., Cox A., Tung M., Chung E.J. Clinical progress of nanomedicine-based RNA therapies. Bioact. Mater. 2022;12:203–213.Lim S.A., Cox A., Tung M., Chung E.J. Clinical progress of nanomedicine-based RNA therapies. Bioact. Mater. 2022;12:203–213.Kanasty R., Dorkin J.R., Vegas A., Anderson D. Delivery materials for siRNA therapeutics. Nat. Mater. 2013;12(11):967–977.Kanasty R., Dorkin J.R., Vegas A., Anderson D. Delivery materials for siRNA therapeutics. Nat. Mater. 2013;12(11):967–977.Juliano RL. The delivery of therapeutic oligonucleotides. Nucleic Acids Res. 2016;44(14):6518–6548.Juliano RL. The delivery of therapeutic oligonucleotides. Nucleic Acids Res. 2016;44(14):6518–6548.Levina A.S., Repkova M.N., Shikina N.V., Ismagilov Z.R., Yashnik S.A., Semenov D.V., Savinovskaya Y.I., Mazurkova N.A., Pyshnaya I.A., Zarytova V.F. Non-agglomerated silicon-organic nanoparticles and their nanocomplexes with oligonucleotides: synthesis and properties. Beilstein J. Nanotechnol. 2018;9:2516–2525.Levina A.S., Repkova M.N., Shikina N.V., Ismagilov Z.R., Yashnik S.A., Semenov D.V., Savinovskaya Y.I., Mazurkova N.A., Pyshnaya I.A., Zarytova V.F. Non-agglomerated silicon-organic nanoparticles and their nanocomplexes with oligonucleotides: synthesis and properties. Beilstein J. Nanotechnol. 2018;9:2516–2525.Levina A.S., Repkova M.N., Klimov L.O., Ryazanova M.A., Markel A.L., Zarytova V.F. Antisense oligonucleotides immobilized on silicon-organic nanoparticles as a tool for prolonged correction of hypertensive states. Bull. Exp. Biol. Med. 2019;167(1):116–119.Levina A.S., Repkova M.N., Klimov L.O., Ryazanova M.A., Markel A.L., Zarytova V.F. Antisense oligonucleotides immobilized on silicon-organic nanoparticles as a tool for prolonged correction of hypertensive states. Bull. Exp. Biol. Med. 2019;167(1):116–119.Levina A., Repkova M., Kupryushkin M., Seryapina A., Shevelev O., Pyshnyi D., Zarytova V. In vivo hypotensive effect of aminosilanol-based nanocomposites bearing antisense oligonucleotides. J. Drug Deliv. Sci. Technol. 2022;75:103612.Levina A., Repkova M., Kupryushkin M., Seryapina A., Shevelev O., Pyshnyi D., Zarytova V. In vivo hypotensive effect of aminosilanol-based nanocomposites bearing antisense oligonucleotides. J. Drug Deliv. Sci. Technol. 2022;75:103612.Osano E., Kishi J., Takahashi Y. Phagocytosis of titanium particles and necrosis in TNF-alpha-resistant mouse sarcoma L929 cells. Toxicol. In Vitro. 2003;17(1):41–47.Osano E., Kishi J., Takahashi Y. Phagocytosis of titanium particles and necrosis in TNF-alpha-resistant mouse sarcoma L929 cells. Toxicol. In Vitro. 2003;17(1):41–47.Levina A.S., Ismagilov Z.R, Repkova M.N., Shikina N.V., Baiborodin S.I., Shatskaia N.V., Zagrebel'nyĭ S.N., Zarytova V.F. TiO2-DNA nanocomposites capable of penetrating into cells. Russian J. Bioorg. Chem. 2013;39(1):77–86.Levina A.S., Ismagilov Z.R, Repkova M.N., Shikina N.V., Baiborodin S.I., Shatskaia N.V., Zagrebel'nyĭ S.N., Zarytova V.F. TiO2-DNA nanocomposites capable of penetrating into cells. Russian J. Bioorg. Chem. 2013;39(1):77–86.Repkova M., Levina A., Chelobanov B., Ismagilov Z., Shatskaya N., Baiborodin S., Filippova E., Mazurkova N., Zarytova V. Efficient inhibition of influenza A viral replication in cells by deoxyribozymes delivered by nanocomposites. Int. J. Antimicrob. Agents. 2017;49(6):703–708.Repkova M., Levina A., Chelobanov B., Ismagilov Z., Shatskaya N., Baiborodin S., Filippova E., Mazurkova N., Zarytova V. Efficient inhibition of influenza A viral replication in cells by deoxyribozymes delivered by nanocomposites. Int. J. Antimicrob. Agents. 2017;49(6):703–708.Li N., Yang H., Yu Z., Li Y., Pan W., Wang H., Tang B. Nuclear-targeted siRNA delivery for long-term gene silencing. Chem. Sci. 2017;8(4):2816–2822.Li N., Yang H., Yu Z., Li Y., Pan W., Wang H., Tang B. Nuclear-targeted siRNA delivery for long-term gene silencing. Chem. Sci. 2017;8(4):2816–2822.Ge Q., Pastey M., Kobasa D., Puthavathana P., Lupfer C., Bestwick R.K., Iversen P.L., Chen J., Stein D.A. Inhibition of multiple subtypes of influenza A virus in cell cultures with morpholino oligomers. Antimicrob. Agents Chemother. 2006;50(11):3724–3733.Ge Q., Pastey M., Kobasa D., Puthavathana P., Lupfer C., Bestwick R.K., Iversen P.L., Chen J., Stein D.A. Inhibition of multiple subtypes of influenza A virus in cell cultures with morpholino oligomers. Antimicrob. Agents Chemother. 2006;50(11):3724–3733.Zhang T., Wang T., Zhao P., Liang M., Gao Y., Yang S., Qin C., Wang C., Xia X. Antisense oligonucleotides targeting the RNA binding region of the NP gene inhibit replication of highly pathogenic avian influenza virus H5N. Int. Immunopharmacol. 2011;11(12):2057–2061.Zhang T., Wang T., Zhao P., Liang M., Gao Y., Yang S., Qin C., Wang C., Xia X. Antisense oligonucleotides targeting the RNA binding region of the NP gene inhibit replication of highly pathogenic avian influenza virus H5N. Int. Immunopharmacol. 2011;11(12):2057–2061.Stoppani E., Bassi I., Dotti S., Lizier M., Ferrari M., Lucchini F. Expression of a single siRNA against a conserved region of NP gene strongly inhibits in vitro replication of different influenza A virus strains of avian and swine origin. Antiviral Res. 2015;120:16–22.Stoppani E., Bassi I., Dotti S., Lizier M., Ferrari M., Lucchini F. Expression of a single siRNA against a conserved region of NP gene strongly inhibits in vitro replication of different influenza A virus strains of avian and swine origin. Antiviral Res. 2015;120:16–22.Liu Y., Lou C., Yang H., Shi M., Miyoshi H. Silica nanoparticles as promising drug/gene delivery carriers and fluorescent nano-probes: recent advances. Curr. Cancer Drug Targets 2011;11(2):156–163.Liu Y., Lou C., Yang H., Shi M., Miyoshi H. Silica nanoparticles as promising drug/gene delivery carriers and fluorescent nano-probes: recent advances. Curr. Cancer Drug Targets 2011;11(2):156–163.Liberman A., Mendez N., Trogler W.C., Kummel A.C. Synthesis and surface functionalization of silica nanoparticles for nanomedicine. Surf. Sci. Rep. 2014;69(2–3):132–158.Liberman A., Mendez N., Trogler W.C., Kummel A.C. Synthesis and surface functionalization of silica nanoparticles for nanomedicine. Surf. Sci. Rep. 2014;69(2–3):132–158.Cheang T.Y., Tang B., Xu A.W., Chang G.Q., Hu Z.J., He W.L., Xing Z.H., Xu J.B., Wang M., Wang S.M. Promising plasmid DNA vector based on APTES-modified silica nanoparticles. Int. J. Nanomedicine 2012;7:1061–1067.Cheang T.Y., Tang B., Xu A.W., Chang G.Q., Hu Z.J., He W.L., Xing Z.H., Xu J.B., Wang M., Wang S.M. Promising plasmid DNA vector based on APTES-modified silica nanoparticles. Int. J. Nanomedicine 2012;7:1061–1067.Mahajan S.D., Law W.C., Aalinkeel R., Reynolds J.L., Nair B.B., Sykes D.E., Yong K.T., Roy I., Prasad P.N., Schwartz S.A. Anti-HIV-1 nanotherapeutics: promises and challenges for the future. Int. J. Nanomed. 2012;7:5301–5314.Mahajan S.D., Law W.C., Aalinkeel R., Reynolds J.L., Nair B.B., Sykes D.E., Yong K.T., Roy I., Prasad P.N., Schwartz S.A. Anti-HIV-1 nanotherapeutics: promises and challenges for the future. Int. J. Nanomed. 2012;7:5301–5314.Chen G., Roy I., Yang C., Prasad P.N. Nanochemistry and nanomedicine for nanoparticle-based diagnostics and therapy. Chem. Rev. 2016;116(5):2826–2885.Chen G., Roy I., Yang C., Prasad P.N. Nanochemistry and nanomedicine for nanoparticle-based diagnostics and therapy. Chem. Rev. 2016;116(5):2826–2885.

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