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

Asya S. Levina, M. Repkova, O.YU. Mazurkov, E. V. Makarevich, N. A. Mazurkova, V. F. Zarytova
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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.
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由二氧化钛纳米颗粒、反义寡核苷酸和光活性基团组成的纳米复合材料,可作为有效作用于核酸的制剂
相关性。对模型系统的研究证实了反义寡核苷酸(包括含有光活性基团的寡核苷酸)对核酸修饰的有效性。然而,由于缺乏成功的细胞传递方法,这一策略尚未得到广泛应用。开发能够作用于细胞中目标核酸的有效制剂是一项紧迫的任务。这项工作的目的是制造由二氧化钛纳米粒子、反义寡核苷酸和光活性基团组成的纳米复合材料,并以抑制甲型流感病毒在细胞系统中的复制为例,研究它们对靶核酸的作用。材料与方法工作中使用了甲型/Aichi/2/68(A/H3N2)流感病毒、对氮基四氟苯甲酸的 N-琥珀酰亚胺醚、TiO2 纳米粒子和寡脱氧核苷酸。在感染了 A/H3N2 病毒的 MDCK 细胞上研究了所提出的纳米复合材料的抗病毒活性。结果与讨论。独特的纳米复合材料由三种功能成分组成,即二氧化钛纳米粒子、反义寡核苷酸和具有光活性的四氟化偶氮酰胺基团。实验证明,纳米复合材料在细胞系统中对甲型流感病毒具有明显的抗病毒特异性作用,其效果超过了不含光活性基团的类似样品。结论所制纳米复合材料的生物活性已通过在细胞系统中高效抑制甲型流感病毒复制的实例得到证实。这些结果表明,利用所提出的药物来影响细胞内的靶核酸具有广阔的前景。
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