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@article{1364900,
author = {Heger, Zbynek and Polanská, Hana and Krizkova, Sona and Balvan, Jan and Raudenská, Martina and Dostalova, Simona and Moulick, Amitava and Masařík, Michal and Adam, Vojtech},
article_location = {Amsterdam},
article_number = {1 February 2017},
doi = {http://dx.doi.org/10.1016/j.colsurfb.2016.11.023},
keywords = {Drug delivery; Etoposide; In vitro release; Multi-walled carbon nanotubes; Nanomedicine},
language = {eng},
issn = {0927-7765},
journal = {Colloids and Surfaces B: Biointerfaces},
title = {Co-delivery of VP-16 and Bcl-2-targeted antisense on PEG-grafted oMWCNTs for synergistic in vitro anti-cancer effects in non-small and small cell lung cancer},
volume = {150},
year = {2017}
}
TY - JOUR
ID - 1364900
AU - Heger, Zbynek - Polanská, Hana - Krizkova, Sona - Balvan, Jan - Raudenská, Martina - Dostalova, Simona - Moulick, Amitava - Masařík, Michal - Adam, Vojtech
PY - 2017
TI - Co-delivery of VP-16 and Bcl-2-targeted antisense on PEG-grafted oMWCNTs for synergistic in vitro anti-cancer effects in non-small and small cell lung cancer
JF - Colloids and Surfaces B: Biointerfaces
VL - 150
IS - 1 February 2017
SP - 131-140
EP - 131-140
PB - Elsevier
SN - 09277765
KW - Drug delivery
KW - Etoposide
KW - In vitro release
KW - Multi-walled carbon nanotubes
KW - Nanomedicine
N2 - Present study describes the preparation of a polyethylene glycol-grafted oxidized multi-walled carbon nanotubes (oMWCNTs-PEG) hybrid nanosystem as a carrier of etoposide (VP-16) and Bcl-2 phosphorothioate antisense deoxyoligonucleotides (Aso) to achieve a superior cytostastic efficacy in non-small and small cell lung cancer in vitro. We have demonstrated that the adsorption of hydrophobic VP-16 and Bcl-2 Aso results in a stable nanotransporter exhibiting good dispersion with excellent release profiles (both, in pH 7.4 and 4.8) and negligible hemolytic activity (up to 6.5%). The evaluation of cytotoxicity was carried out in in vitro using small cell (SCLC; DMS53) and non-small cell lung cancer (NSCLC; NCIH2135) cell lines. It was found that Bcl-2 interference significantly increased the anti-cancer efficiency of VP-16 in the chemoresistant NSCLC cells. This was further supported using a flow-cytometry (Annexin V/propidium iodide assay), which revealed a significant increase in apoptotic cells in both the cell lines after the co-administration of VP-16 and Bcl-2 Aso using oMWCNTs-PEG hybrid, and fluorescence microscopy, which showed an increase in reactive oxygen species identified after Bcl-2 knock-down. Overall, oMWCNTs-PEG provided an exceptional biocompatible vehicle enabling the internalization of negatively charged nucleic acids and pH-sensitive release of cargoes in a hypoxic environment of the most of solid tumors. Moreover, Aso specifically binding to the first six codons of the Bcl-2 mRNA gave a satisfactorily decrease in Bcl-2 translation and an increase in NCIH2135 chemosensitivity towards VP-16.
ER -
HEGER, Zbynek, Hana POLANSKÁ, Sona KRIZKOVA, Jan BALVAN, Martina RAUDENSKÁ, Simona DOSTALOVA, Amitava MOULICK, Michal MASAŘÍK a Vojtech ADAM. Co-delivery of VP-16 and Bcl-2-targeted antisense on PEG-grafted oMWCNTs for synergistic in vitro anti-cancer effects in non-small and small cell lung cancer. \textit{Colloids and Surfaces B: Biointerfaces}. Amsterdam: Elsevier, roč.~150, 1 February 2017, s.~131-140. ISSN~0927-7765. doi:10.1016/j.colsurfb.2016.11.023. 2017.
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