Non-agglomerated oligonucleotide-containing nanocomposites based on titanium dioxide nanoparticles

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Abstract

Stability and monodispersity are important properties of nanoparticles and nanocomposites that ensure the reliability of their application in biological systems and the reproducibility of results. The preparation of non-agglomerated oligonucleotide-containing nanocomposites based on anatase titanium dioxide nanoparticles (Ans~ODN) is the aim of this work. The immobilization of oligodeoxynucleotides on TiO2 nanoparticles has been studied by the dynamic light scattering and transmission electron microscopy. The antiviral activity of the synthesized samples has been performed on VERO cells infected with herpes simplex virus of the first type. The effect of NaCl on the agglomeration of nanoparticles and nanocomposites in aqueous solutions has been studied. The presence of NaCl leads to agglomeration of nanoparticles and nanocomposites. It has been shown that nanocomposites are formed in an aqueous solution in the absence of NaCl. A comparison of the biological activity of nanocomposites prepared in water and saline solution has been carried out with an example of inhibition of replication of the herpes simplex virus of the first type in the cell culture. The studied nanocomposite, regardless of the preparation method (in water or 0.9% NaCl), inhibited virus replication by 4.5 orders of magnitude when used 1 day after preparation. After 10 days of storage, the activity of the sample prepared in saline solution was two orders of magnitude lower than that of the active sample prepared in water. We have developed the method for the preparation of non-agglomerated oligonucleotide-containing nanocomposites based on anatase nanoparticles and demonstrated their potential use for the study of their biological activity. Unlike nanocomposites prepared in the presence of salt, which lose their efficacy during storage, nanocomposites that are not prone to agglomeration can be obtained in water for future use.

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About the authors

M. N. Repkova

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

Email: asl1032@yandex.ru
Russian Federation, prosp. Lavrent’eva 8, Novosibirsk, 630090

O. Y. Mazurkov

FBRI State Research Center of Virology and Biotechnology “Vector”

Email: asl1032@yandex.ru
Russian Federation, Koltsovo, Novosibirsk region, 630559

E. I. Filippova

FBRI State Research Center of Virology and Biotechnology “Vector”

Email: asl1032@yandex.ru
Russian Federation, Koltsovo, Novosibirsk region, 630559

N. A. Mazurkova

FBRI State Research Center of Virology and Biotechnology “Vector”

Email: asl1032@yandex.ru
Russian Federation, Koltsovo, Novosibirsk region, 630559

Yu. E. Poletaeva

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

Email: asl1032@yandex.ru
Russian Federation, prosp. Lavrent’eva 8, Novosibirsk, 630090

E. I. Ryabchikova

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

Email: asl1032@yandex.ru
Russian Federation, prosp. Lavrent’eva 8, Novosibirsk, 630090

B. F. Zarytova

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

Email: asl1032@yandex.ru
Russian Federation, prosp. Lavrent’eva 8, Novosibirsk, 630090

A. S. Levina

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

Author for correspondence.
Email: asl1032@yandex.ru
Russian Federation, prosp. Lavrent’eva 8, Novosibirsk, 630090

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2. Fig. 1. Scheme of formation of Ans/PL-ODN nanocomposites.

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3. Fig. 2. Particle size distribution according to DLS data 1–2 h (a) and 3 months (b) after sample preparation. 1 – Ans, 2 – Ans/PL, 3 – Ans/PL-ODN. Concentration of particles and nanocomposites – 0.1 mg/ml based on Ans.

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4. Fig. 3. Ultrastructure of Ans, Ans/PL, and Ans/PL•ODN nanoparticle suspensions obtained by TEM: (a) – aqueous suspension of Ans nanoparticles. Inset – particles of medium electron density, rounded electron-dense particle is shown by arrow; (b) and (c) – aqueous suspensions of Ans/PL and Ans/PL•ODN nanoparticles. Cavities of closed rounded profiles are shown by asterisks. Areas of dense arrangement of nanoparticles are highlighted by circles; (d) – suspension of Ans nanoparticles in 0.9% NaCl solution. Inset shows enlarged area of ​​accumulation, “glued” particles are visible; (d) and (e) – suspensions of Ans/PL and Ans/PL•ODN nanoparticles. Sorption of suspension on mesh. Length of scale bars is 100 nm.

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