Composites of Peptide Nucleic Acids with Titanium Dioxide Nanoparticles. IV+. Antiviral Activity of Nanocomposites Containing DNA/PNA Duplexes

Abstract

Antiviral activity of TiO2 · PL · DNA/PNA nanobiocomposites was studied on the MDCK cell culture infected with influenza A virus (subtype H3N2). PNA fragment in nanocomposites as a DNA/PNA heteroduplex is electrostatically bound to titanium dioxide nanoparticles precovered with polylysine (TiO2 · PL). It was shown that TiO2 · PL · DNA1/PNA1 nanobiocomposit bearing PNA1 fragment targeted to the 3'-end of the noncoding region of segment 5 of viral RNA specifically inhibited the virus reproduction with the efficiency of 99.8%. It was determined that the 50% cytotoxic concentration (TC50) of the TiO2 · PL · DNA1/PNA1 nanocomposite is more than 1200 mg/mL. And 50% effective inhibitory concentration (IC50) is less than 0.003 mg/mL. Based on these data, the selectivity index (SI) for TiO2 · PL · DNA1/PNA1 nanobiocomposite defined as the ratio TC50/LC50, is more than 400. Thus TiO2 · PL · DNA/PNA nanobiocomposites can not only penatrate through cell membrane, but and are able to exhibit a high specific antisense activity, without causing toxic effects on the living cells.