Nanocomposites consisting of titanium dioxide nanoparticles, antisense oligonucleotides, and photoactive groups as agents for effective action on nucleic acids

Relevance. Studies on model systems have confirmed the effectiveness of antisense oligonucleotides, including those that contain photoactive groups, for the modification of nucleic acids. However, this strategy has not yet found wide application due to the lack of successful methods for the cellular...

Full description

Bibliographic Details
Main Authors: Asya S. Levina, Marina N. Repkova, Oleg Y. Mazurkov, Elena V. Makarevich, Natalya A. Mazurkova, Valentina F. Zarytova
Format: Article
Language:Russian
Published: Central Research Institute for Epidemiology 2024-03-01
Series:Журнал микробиологии, эпидемиологии и иммунобиологии
Subjects:
Online Access:https://microbiol.crie.ru/jour/article/viewFile/17775/1409
_version_ 1797257157620531200
author Asya S. Levina
Marina N. Repkova
Oleg Y. Mazurkov
Elena V. Makarevich
Natalya A. Mazurkova
Valentina F. Zarytova
author_facet Asya S. Levina
Marina N. Repkova
Oleg Y. Mazurkov
Elena V. Makarevich
Natalya A. Mazurkova
Valentina F. Zarytova
author_sort Asya S. Levina
collection DOAJ
description Relevance. Studies on model systems have confirmed the effectiveness of antisense oligonucleotides, including those that contain photoactive groups, for the modification of nucleic acids. However, this strategy has not yet found wide application due to the lack of successful methods for the cellular delivery. The development of effective preparations capable of acting on target nucleic acids in cells is an urgent task. The objective of the work is to create nanocomposites consisting of TiO2 nanoparticles, antisense oligonucleotides, and photoactive groups and to study their effect on target nucleic acids by the example of inhibition of influenza A virus replication in the cellular system. Materials and methods. Influenza virus A/Aichi/2/68 (A/H3N2), N-succinimide ether of p-azidotetrafluorobenzoic acid, TiO2 nanoparticles, and oligodeoxyribonucleotides have been used in the work. The antiviral activity of the proposed nanocomposites has been studied on the MDCK cells infected with the A/H3N2 virus. Results and discussion. Unique nanocomposites have been created, which consist of three functional components, i.e., titanium dioxide nanoparticles, antisense oligonucleotides, and the photoactive tetrafluoroarylazide group, respectively, providing penetration into cells, selective interaction with target nucleic acids, and photomodification of the targets. A significant antiviral site-specific action of the nanocomposites has been demonstrated against the influenza A virus in the cellular system, which exceeds the effect of the analogous samples that contain no photoactive groups. Conclusion. The biological activity of the created nanocomposites has been demonstrated by the example of highly effective suppression of influenza A virus replication in the cellular system. The results indicate the prospects of using the proposed drugs to affect target nucleic acids inside cells.
first_indexed 2024-04-24T22:33:11Z
format Article
id doaj.art-f25b4af22a2c41089734f6a6c3a2b404
institution Directory Open Access Journal
issn 0372-9311
2686-7613
language Russian
last_indexed 2024-04-24T22:33:11Z
publishDate 2024-03-01
publisher Central Research Institute for Epidemiology
record_format Article
series Журнал микробиологии, эпидемиологии и иммунобиологии
spelling doaj.art-f25b4af22a2c41089734f6a6c3a2b4042024-03-19T14:53:29ZrusCentral Research Institute for EpidemiologyЖурнал микробиологии, эпидемиологии и иммунобиологии0372-93112686-76132024-03-01101112713210.36233/0372-9311-4562737Nanocomposites consisting of titanium dioxide nanoparticles, antisense oligonucleotides, and photoactive groups as agents for effective action on nucleic acidsAsya S. Levina0https://orcid.org/0000-0003-2423-3805Marina N. Repkova1https://orcid.org/0000-0002-7108-9036Oleg Y. Mazurkov2https://orcid.org/0000-0001-8164-4091Elena V. Makarevich3https://orcid.org/0000-0002-5146-8979Natalya A. Mazurkova4https://orcid.org/0000-0002-1896-2684Valentina F. Zarytova5https://orcid.org/0000-0002-9579-9972Institute of Chemical Biology and Fundamental MedicineInstitute of Chemical Biology and Fundamental MedicineState Research Center of Virology and Biotechnology “Vector"State Research Center of Virology and Biotechnology “Vector"State Research Center of Virology and Biotechnology “Vector"Institute of Chemical Biology and Fundamental MedicineRelevance. Studies on model systems have confirmed the effectiveness of antisense oligonucleotides, including those that contain photoactive groups, for the modification of nucleic acids. However, this strategy has not yet found wide application due to the lack of successful methods for the cellular delivery. The development of effective preparations capable of acting on target nucleic acids in cells is an urgent task. The objective of the work is to create nanocomposites consisting of TiO2 nanoparticles, antisense oligonucleotides, and photoactive groups and to study their effect on target nucleic acids by the example of inhibition of influenza A virus replication in the cellular system. Materials and methods. Influenza virus A/Aichi/2/68 (A/H3N2), N-succinimide ether of p-azidotetrafluorobenzoic acid, TiO2 nanoparticles, and oligodeoxyribonucleotides have been used in the work. The antiviral activity of the proposed nanocomposites has been studied on the MDCK cells infected with the A/H3N2 virus. Results and discussion. Unique nanocomposites have been created, which consist of three functional components, i.e., titanium dioxide nanoparticles, antisense oligonucleotides, and the photoactive tetrafluoroarylazide group, respectively, providing penetration into cells, selective interaction with target nucleic acids, and photomodification of the targets. A significant antiviral site-specific action of the nanocomposites has been demonstrated against the influenza A virus in the cellular system, which exceeds the effect of the analogous samples that contain no photoactive groups. Conclusion. The biological activity of the created nanocomposites has been demonstrated by the example of highly effective suppression of influenza A virus replication in the cellular system. The results indicate the prospects of using the proposed drugs to affect target nucleic acids inside cells.https://microbiol.crie.ru/jour/article/viewFile/17775/1409tio2 nanoparticlesnanocompositesoligonucleotidesphotoactive groupsantiviral activity
spellingShingle Asya S. Levina
Marina N. Repkova
Oleg Y. Mazurkov
Elena V. Makarevich
Natalya A. Mazurkova
Valentina F. Zarytova
Nanocomposites consisting of titanium dioxide nanoparticles, antisense oligonucleotides, and photoactive groups as agents for effective action on nucleic acids
Журнал микробиологии, эпидемиологии и иммунобиологии
tio2 nanoparticles
nanocomposites
oligonucleotides
photoactive groups
antiviral activity
title Nanocomposites consisting of titanium dioxide nanoparticles, antisense oligonucleotides, and photoactive groups as agents for effective action on nucleic acids
title_full Nanocomposites consisting of titanium dioxide nanoparticles, antisense oligonucleotides, and photoactive groups as agents for effective action on nucleic acids
title_fullStr Nanocomposites consisting of titanium dioxide nanoparticles, antisense oligonucleotides, and photoactive groups as agents for effective action on nucleic acids
title_full_unstemmed Nanocomposites consisting of titanium dioxide nanoparticles, antisense oligonucleotides, and photoactive groups as agents for effective action on nucleic acids
title_short Nanocomposites consisting of titanium dioxide nanoparticles, antisense oligonucleotides, and photoactive groups as agents for effective action on nucleic acids
title_sort nanocomposites consisting of titanium dioxide nanoparticles antisense oligonucleotides and photoactive groups as agents for effective action on nucleic acids
topic tio2 nanoparticles
nanocomposites
oligonucleotides
photoactive groups
antiviral activity
url https://microbiol.crie.ru/jour/article/viewFile/17775/1409
work_keys_str_mv AT asyaslevina nanocompositesconsistingoftitaniumdioxidenanoparticlesantisenseoligonucleotidesandphotoactivegroupsasagentsforeffectiveactiononnucleicacids
AT marinanrepkova nanocompositesconsistingoftitaniumdioxidenanoparticlesantisenseoligonucleotidesandphotoactivegroupsasagentsforeffectiveactiononnucleicacids
AT olegymazurkov nanocompositesconsistingoftitaniumdioxidenanoparticlesantisenseoligonucleotidesandphotoactivegroupsasagentsforeffectiveactiononnucleicacids
AT elenavmakarevich nanocompositesconsistingoftitaniumdioxidenanoparticlesantisenseoligonucleotidesandphotoactivegroupsasagentsforeffectiveactiononnucleicacids
AT natalyaamazurkova nanocompositesconsistingoftitaniumdioxidenanoparticlesantisenseoligonucleotidesandphotoactivegroupsasagentsforeffectiveactiononnucleicacids
AT valentinafzarytova nanocompositesconsistingoftitaniumdioxidenanoparticlesantisenseoligonucleotidesandphotoactivegroupsasagentsforeffectiveactiononnucleicacids