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Composites of peptide nucleic acids with titanium dioxide nanoparticles. IV. Antiviral activity of nanocomposites containing DNA/PNA duplexes

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Abstract

Antiviral activity of TiO2 · PL · DNA/PNA nanobiocomposites was studied on the MDCK cell culture infected with influenza A virus (H3N2 subtype). A PNA fragment in nanocomposites was electrostatically bound in the form of a DNA/PNA heteroduplex to titanium dioxide nanoparticles precovered with polylysine (TiO2 · PL). It was shown that TiO2 · PL · DNA1/PNA1 nanobiocomposite bearing the PNA1 fragment targeted to the 3′-end of the noncoding region of segment 5 of viral RNA specifically inhibited the virus reproduction with an efficiency of 99.8%. The 50% cytotoxic concentration (TC50) and 50% effective inhibitory concentration (IC50) of the TiO2 · PL · DNA1/PNA1 nanocomposite were evaluated to be more than 1200 μg/mL and less than 3 μg/mL, respectively. Based on these data, the selectivity index (SI) for TiO2 · PL · DNA1/PNA1 nanobiocomposite defined as the TC50/IC50 ratio, was calculated to be more than 400. Thus, TiO2 · PL · DNA/PNA nanobiocomposites were shown to not only penetrate through cell membranes, but exhibit a high specific antisense activity without toxic effects on the living cells.

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Abbreviations

TC50 :

50% cytotoxic concentration

IC50 :

50% effective concentration

NI:

neutralization index as the difference of logarithms of the virus titer in the absence (control) and the presence (sample) of the nanocomposites

PL:

poly-L-lysine

SI:

selectivity index as the ratio of TC50 to IC50

vRNA:

viral RNA

mRNA:

messenger RNA complementary to vRNA

cRNA:

replication copy of vRNA

PNA:

peptide nucleic acid

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Authors and Affiliations

  1. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of RAS, pr. Lavrent’eva 8, Novosibirsk, 630090, Russia

    R. N. Amirkhanov, N. V. Amirkhanov & V. F. Zarytova

  2. Novosibirsk State University, ul. Pirogova 2, Novosibirsk, 630090, Russia

    R. N. Amirkhanov

  3. FBRI State Research Center of Virology and Biotechnology “Vector”, Koltsovo, Novosibirsk oblast, Russia

    N. A. Mazurkova

Authors
  1. R. N. Amirkhanov
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  2. N. A. Mazurkova
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  3. N. V. Amirkhanov
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  4. V. F. Zarytova
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Corresponding author

Correspondence to V. F. Zarytova.

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Original Russian Text © R.N. Amirkhanov, N.A. Mazurkova, N.V. Amirkhanov, V.F. Zarytova, 2015, published in Bioorganicheskaya Khimiya, 2015, Vol. 41, No. 2, pp. 162–169.

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Amirkhanov, R.N., Mazurkova, N.A., Amirkhanov, N.V. et al. Composites of peptide nucleic acids with titanium dioxide nanoparticles. IV. Antiviral activity of nanocomposites containing DNA/PNA duplexes. Russ J Bioorg Chem 41, 140–146 (2015). https://doi.org/10.1134/S1068162015020028

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  • DOI: https://doi.org/10.1134/S1068162015020028

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