title: High-performance method for specific effect on nucleic acids in cells using TiO2~DNA nanocomposites.
abstract: Nanoparticles are used to solve the current drug delivery problem. We present a high-performance method for efficient and selective action on nucleic acid target in cells using unique TiO(2)·PL-DNA nanocomposites (polylysine-containing DNA fragments noncovalently immobilized onto TiO(2) nanoparticles capable of transferring DNA). These nanocomposites were used for inhibition of human influenza A (H3N2) virus replication in infected MDCK cells. They showed a low toxicity (TC(50) ≈ 1800 μg/ml) and a high antiviral activity (>99.9% inhibition of the virus replication). The specificity factor (antisense effect) appeared to depend on the delivery system of DNA fragments. This factor for nanocomposites is ten-times higher than for DNA in the presence of lipofectamine. IC(50) for nanocomposites was estimated to be 1.5 μg/ml (30 nM for DNA), so its selectivity index was calculated as ~1200. Thus, the proposed nanocomposites are prospective for therapeutic application.
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia.
authors.forename: Asya S
authors.initials: AS
authors.lastname: Levina
authors.forename: Marina N
authors.initials: MN
authors.lastname: Repkova
authors.forename: Zinfer R
authors.initials: ZR
authors.lastname: Ismagilov
authors.forename: Nadezhda V
authors.initials: NV
authors.lastname: Shikina
authors.forename: Ernst G
authors.initials: EG
authors.lastname: Malygin
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Mazurkova
authors.forename: Victor V
authors.initials: VV
authors.lastname: Zinov'ev
authors.forename: Alexei A
authors.initials: AA
authors.lastname: Evdokimov
authors.forename: Sergei I
authors.initials: SI
authors.lastname: Baiborodin
authors.forename: Valentina F
authors.initials: VF
authors.lastname: Zarytova
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000138:chemical synthesis / Q000494:pharmacology*; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects* / Q000254:growth & development; D020128:Inhibitory Concentration 50; D061985:Madin Darby Canine Kidney Cells; D053768:Metal Nanoparticles / Q000737:chemistry; D053761:Nanocomposites / Q000737:chemistry*; D011107:Polylysine / Q000737:chemistry*; D012367:RNA, Viral / Q000037:antagonists & inhibitors* / Q000235:genetics; D014025:Titanium / Q000737:chemistry*; D019562:Viral Load / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D020413:3' Untranslated Regions; D000998:Antiviral Agents; D052157:Aptamers, Nucleotide; D004337:Drug Carriers; D012367:RNA, Viral; C009495:titanium dioxide; D011107:Polylysine; D014025:Titanium