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

Antiviral activity of TiO2 center dot PL center dot 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 center dot PL). It was shown that TiO2 center dot PL center dot 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 (TC50) and 50% effective inhibitory concentration (IC50) of the TiO2 center dot PL center dot DNA(1)/PNA(1) nanocomposite were evaluated to be more than 1200 mu g/mL and less than 3 mu g/mL, respectively. Based on these data, the selectivity index (SI) for TiO2 center dot PL center dot DNA(1)/PNA(1) nanobiocomposite defined as the TC50/IC50 ratio, was calculated to be more than 400. Thus, TiO2 center dot PL center dot 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.