tetano
Editor, Senior Moderator
Int J Antimicrob Agents. 2017 Apr 12. pii: S0924-8579(17)30113-9. doi: 10.1016/j.ijantimicag.2017.01.026. [Epub ahead of print]
[h=1]Efficient inhibition of influenza A viral replication in cells by deoxyribozymes delivered by nanocomposites.[/h] Repkova M[SUP]1[/SUP], Levina A[SUP]1[/SUP], Chelobanov B[SUP]2[/SUP], Ismagilov Z[SUP]3[/SUP], Shatskaya N[SUP]4[/SUP], Baiborodin S[SUP]4[/SUP], Filippova E[SUP]5[/SUP], Mazurkova N[SUP]5[/SUP], Zarytova V[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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 TiO[SUB]2[/SUB]-based nanocomposites. For the first time, unmodified Dz molecules were non-covalently immobilized on TiO[SUB]2[/SUB] nanoparticles precovered with polylysine (TiO[SUB]2[/SUB]?PL) with the formation of (TiO[SUB]2[/SUB]?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 (TiO[SUB]2[/SUB]?PL)?Dz[SUP]Flu[/SUP] nanocomposites penetrate into eukaryotic cells, where Dz[SUP]Flu[/SUP] 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 when using lipofectamine as the transfection agent compared with TiO[SUB]2[/SUB] nanoparticles. The proposed (TiO[SUB]2[/SUB]?PL)?Dz nanocomposites demonstrated high antiviral activity and are thus potent as nucleic-acid-based drugs.
Copyright ? 2017. Published by Elsevier B.V.
[h=4]KEYWORDS:[/h] Cell delivery; DNAzymes; Gene silencing; Immobilization; Influenza A virus; TiO2-based nanocomposites
PMID: 28412273 DOI: 10.1016/j.ijantimicag.2017.01.026
[h=1]Efficient inhibition of influenza A viral replication in cells by deoxyribozymes delivered by nanocomposites.[/h] Repkova M[SUP]1[/SUP], Levina A[SUP]1[/SUP], Chelobanov B[SUP]2[/SUP], Ismagilov Z[SUP]3[/SUP], Shatskaya N[SUP]4[/SUP], Baiborodin S[SUP]4[/SUP], Filippova E[SUP]5[/SUP], Mazurkova N[SUP]5[/SUP], Zarytova V[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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 TiO[SUB]2[/SUB]-based nanocomposites. For the first time, unmodified Dz molecules were non-covalently immobilized on TiO[SUB]2[/SUB] nanoparticles precovered with polylysine (TiO[SUB]2[/SUB]?PL) with the formation of (TiO[SUB]2[/SUB]?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 (TiO[SUB]2[/SUB]?PL)?Dz[SUP]Flu[/SUP] nanocomposites penetrate into eukaryotic cells, where Dz[SUP]Flu[/SUP] 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 when using lipofectamine as the transfection agent compared with TiO[SUB]2[/SUB] nanoparticles. The proposed (TiO[SUB]2[/SUB]?PL)?Dz nanocomposites demonstrated high antiviral activity and are thus potent as nucleic-acid-based drugs.
Copyright ? 2017. Published by Elsevier B.V.
[h=4]KEYWORDS:[/h] Cell delivery; DNAzymes; Gene silencing; Immobilization; Influenza A virus; TiO2-based nanocomposites
PMID: 28412273 DOI: 10.1016/j.ijantimicag.2017.01.026