Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Efficient inhibition of influenza A viral replication in cells by deoxyribozymes delivered by nanocomposites. / Repkova, Marina; Levina, Asya; Chelobanov, Boris и др.
в: International Journal of Antimicrobial Agents, Том 49, № 6, 01.06.2017, стр. 703-708.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - Efficient inhibition of influenza A viral replication in cells by deoxyribozymes delivered by nanocomposites
AU - Repkova, Marina
AU - Levina, Asya
AU - Chelobanov, Boris
AU - Ismagilov, Zinfer
AU - Shatskaya, Natalia
AU - Baiborodin, Sergei
AU - Filippova, Ekaterina
AU - Mazurkova, Natalia
AU - Zarytova, Valentina
N1 - Publisher Copyright: © 2017 Elsevier B.V. and International Society of Chemotherapy
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Nucleic-acid-based drugs are a promising class of novel therapeutics; however, their use in medicine is widely limited because of insufficient delivery into cells. This article proposes a new delivery strategy of nucleic acid fragments into cells as components of TiO2-based nanocomposites. For the first time, unmodified Dz molecules were non-covalently immobilized on TiO2 nanoparticles precovered with polylysine (TiO2•PL) with the formation of (TiO2•PL)•Dz nanocomposites. DNAzymes in the proposed nanocomposites were shown to retain their ability to cleave the RNA target in a cell-free system with the same selectivity as unbound Dz molecules. It was shown by confocal laser microscopy that the fluorescein-labelled (TiO2•PL)•DzFlu nanocomposites penetrate into eukaryotic cells, where DzFlu is internalized in the cytoplasm and predominantly in nuclei. Delivery of deoxyribozymes into cells in the proposed nanocomposites permits very efficient interactions with RNA targets inside cells. This was demonstrated by an example of inhibition of H5N1 influenza A virus replication (inhibition by a factor of ca. 3000). This effect was one order of magnitude higher than with using lipofectamine as the transfection agent. The proposed (TiO2•PL)•Dz nanocomposites demonstrated high antiviral activity and are thus potent as nucleic-acid-based drugs.
AB - Nucleic-acid-based drugs are a promising class of novel therapeutics; however, their use in medicine is widely limited because of insufficient delivery into cells. This article proposes a new delivery strategy of nucleic acid fragments into cells as components of TiO2-based nanocomposites. For the first time, unmodified Dz molecules were non-covalently immobilized on TiO2 nanoparticles precovered with polylysine (TiO2•PL) with the formation of (TiO2•PL)•Dz nanocomposites. DNAzymes in the proposed nanocomposites were shown to retain their ability to cleave the RNA target in a cell-free system with the same selectivity as unbound Dz molecules. It was shown by confocal laser microscopy that the fluorescein-labelled (TiO2•PL)•DzFlu nanocomposites penetrate into eukaryotic cells, where DzFlu is internalized in the cytoplasm and predominantly in nuclei. Delivery of deoxyribozymes into cells in the proposed nanocomposites permits very efficient interactions with RNA targets inside cells. This was demonstrated by an example of inhibition of H5N1 influenza A virus replication (inhibition by a factor of ca. 3000). This effect was one order of magnitude higher than with using lipofectamine as the transfection agent. The proposed (TiO2•PL)•Dz nanocomposites demonstrated high antiviral activity and are thus potent as nucleic-acid-based drugs.
KW - Cell delivery
KW - DNAzymes
KW - Gene silencing
KW - Immobilization
KW - Influenza A virus
KW - TiO-based nanocomposites
KW - TiO2-based nanocomposites
KW - TOXICITY
KW - TITANIUM-DIOXIDE NANOPARTICLES
KW - NUCLEIC-ACIDS
KW - Humans
KW - Virus Replication/drug effects
KW - Influenza A Virus, H5N1 Subtype/drug effects
KW - DNA, Catalytic/metabolism
KW - Drug Carriers/metabolism
KW - Animals
KW - Nanocomposites
KW - Dogs
KW - Madin Darby Canine Kidney Cells
KW - HeLa Cells
KW - Antiviral Agents/metabolism
KW - Metal Nanoparticles
KW - TiO -based nanocomposites
UR - http://www.scopus.com/inward/record.url?scp=85017517124&partnerID=8YFLogxK
U2 - 10.1016/j.ijantimicag.2017.01.026
DO - 10.1016/j.ijantimicag.2017.01.026
M3 - Article
C2 - 28412273
AN - SCOPUS:85017517124
VL - 49
SP - 703
EP - 708
JO - International Journal of Antimicrobial Agents
JF - International Journal of Antimicrobial Agents
SN - 0924-8579
IS - 6
ER -
ID: 8673050