Publication detail

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

HEGER, Z. POLANSKÁ, H. KŘÍŽKOVÁ, S. BALVAN, J. RAUDENSKÁ, M. DOSTÁLOVÁ, S. MOULICK, A. MASAŘÍK, M. ADAM, V.

Original 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

Type

journal article in Web of Science

Language

English

Original Abstract

Present study describes the preparation of a polyethylene glycol-grafted oxidized multi-walled carbonnanotubes (oMWCNTs-PEG) hybrid nanosystem as a carrier of etoposide (VP-16) and Bcl-2 phosphoroth-ioate antisense deoxyoligonucleotides (Aso) to achieve a superior cytostastic efficacy in non-small andsmall cell lung cancer in vitro. We have demonstrated that the adsorption of hydrophobic VP-16 and Bcl-2Aso 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 car-ried out in in vitro using small cell (SCLC; DMS53) and non-small cell lung cancer (NSCLC; NCIH2135) celllines. It was found that Bcl-2 interference significantly increased the anti-cancer efficiency of VP-16 in thechemoresistant NSCLC cells. This was further supported using a flow-cytometry (Annexin V/propidiumiodide 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, whichshowed 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 chargednucleic 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 decreasein Bcl-2 translation and an increase in NCIH2135 chemosensitivity towards VP-16.

Keywords

Drug delivery; Etoposide; In vitro release; Multi-walled carbon nanotubes; Nanomedicine

Authors

HEGER, Z.; POLANSKÁ, H.; KŘÍŽKOVÁ, S.; BALVAN, J.; RAUDENSKÁ, M.; DOSTÁLOVÁ, S.; MOULICK, A.; MASAŘÍK, M.; ADAM, V.

Released

1. 2. 2017

ISBN

0927-7765

Periodical

Colloids and Surfaces B: Biointerfaces

Year of study

150

Number

1

State

Kingdom of the Netherlands

Pages from

131

Pages to

140

Pages count

10

BibTex

@article{BUT133993,
  author="HEGER, Z. and POLANSKÁ, H. and KŘÍŽKOVÁ, S. and BALVAN, J. and RAUDENSKÁ, M. and DOSTÁLOVÁ, S. and MOULICK, A. and MASAŘÍK, M. and ADAM, V.",
  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",
  journal="Colloids and Surfaces B: Biointerfaces",
  year="2017",
  volume="150",
  number="1",
  pages="131--140",
  doi="10.1016/j.colsurfb.2016.11.023",
  issn="0927-7765"
}