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

Antiviral activity of TiO 2 · 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 (TiO 2 · PL). It was shown that TiO 2 · PL · DNA 1 /PNA 1 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 (TC 50 ) and 50% effective inhibitory concentration (IC 50 ) of the TiO 2 · PL · DNA 1 /PNA 1 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 TiO 2 · PL · DNA 1 /PNA 1 nanobiocomposite defined as the TC 50 /IC 50 ratio, was calculated to be more than 400. Thus, TiO 2 · 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.