Nanoparticle-Mediated Nonviral DNA Delivery for Effective Inhibition of Influenza a Viruses in Cells


Development of new antiviral nucleic acid-primarily based medication and the search for their efficient delivery into cells are an urgent task. We tend to ready the TiO2·PL-DNA and TiO2·PL±DNA nanocomposites bearing DNA fragments immobilized on TiO2 nanoparticles through polylysine linker (PL) with either covalent or ionic bond between PL and DNA, respectively. The proposed nanocomposites will penetrate into cells while not transfection agents. The DNA fragments in both types of the nanocomposites were shown to retain their ability to make complementary complexes. The nanocomposites TiO2·PL-dsDNA and TiO2·PL±dsDNA bearing the double-stranded DNA were additionally synthesized. The proposed nanocomposites were demonstrated to be economical antiviral agents against influenza A virus (IAV) in the MDCK cell culture. The TiO2·PL-DNA and TiO two·PL±DNA nanocomposites bearing the DNA fragments targeted to the 3'-noncoding region of IAV section 5 inhibited virus replication by four and 3 orders of magnitude, respectively. Therefore, the TiO2 ·PL-DNA nanocomposites gave the impression to be more efficient than the TiO2·PL±DNA nanocomposites. The antiviral activity of the nanocomposites can be improved by either increasing their capability for the DNA fragment or using dsDNA. Control samples, i.e., nanoparticles without DNA fragments and vice versa, unbound DNA fragments in the presence of nanoparticles, and nanocomposites bearing DNA fragments with random sequences showed a negligible result. The presented nanocomposites will be applied in the thriving technology of drug delivery to attain high therapeutic and biological efficacy.

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