TY - JOUR

T1 - Nuclear delivery of oligonucleotides via nanocomposites based on TiO2 nanoparticles and polylysine

AU - Chelobanov, B. P.

AU - Repkova, M. N.

AU - Baiborodin, S. I.

AU - Ryabchikova, E. I.

AU - Stetsenko, D. A.

N1 - Publisher Copyright: © 2017, Pleiades Publishing, Inc.

PY - 2017/9/1

Y1 - 2017/9/1

N2 - The nuclear delivery of nucleic acid derivatives is an essential prerequisite for successful antisense therapy. Using laser confocal and electron microscopy, we have studied the uptake of fluorescently labeled oligonucleotides in the form of nanocomposites with polylysine and TiO2 nanoparticles into Caco2, MDCK, and HeLa cells. In all three cell lines, bright fluorescence has been detected after 30 min in the nuclei (excluding the nucleoli) of the interphase cells; no substantial increase in the intensity of the signal was observed for next 24 hours. In all cells undergoing mitosis, the signal was localized in the cytoplasm with zones of higher intensity around chromatin. In some cells, at the beginning of interphase (G-1 phase), fluorescence was not detected at all. The latter may be explained by the brief moment in the cell cycle when oligonucleotides delivered in the nanocomposite cannot be taken up by cells. The studied nanocomposites are prone to aggregation. The degree of aggregation increases with the storage time up to complete loss of the ability of the nanocomposites to penetrate the cells.

AB - The nuclear delivery of nucleic acid derivatives is an essential prerequisite for successful antisense therapy. Using laser confocal and electron microscopy, we have studied the uptake of fluorescently labeled oligonucleotides in the form of nanocomposites with polylysine and TiO2 nanoparticles into Caco2, MDCK, and HeLa cells. In all three cell lines, bright fluorescence has been detected after 30 min in the nuclei (excluding the nucleoli) of the interphase cells; no substantial increase in the intensity of the signal was observed for next 24 hours. In all cells undergoing mitosis, the signal was localized in the cytoplasm with zones of higher intensity around chromatin. In some cells, at the beginning of interphase (G-1 phase), fluorescence was not detected at all. The latter may be explained by the brief moment in the cell cycle when oligonucleotides delivered in the nanocomposite cannot be taken up by cells. The studied nanocomposites are prone to aggregation. The degree of aggregation increases with the storage time up to complete loss of the ability of the nanocomposites to penetrate the cells.

KW - cell delivery

KW - deoxyribozyme (DNAzyme)

KW - electron microscopy

KW - scanning confocal laser microscopy

UR - http://www.scopus.com/inward/record.url?scp=85031431809&partnerID=8YFLogxK

U2 - 10.1134/S0026893317050065

DO - 10.1134/S0026893317050065

M3 - Article

AN - SCOPUS:85031431809

VL - 51

SP - 695

EP - 704

JO - Molecular Biology

JF - Molecular Biology

SN - 0026-8933

IS - 5

ER -