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

Abstract

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.