HEGER, Zbynek, Hana POLANSKÁ, Sona KRIZKOVA, Jan BALVAN, Martina RAUDENSKÁ, Simona DOSTALOVA, Amitava MOULICK, Michal MASAŘÍK and 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. Colloids and Surfaces B: Biointerfaces. Amsterdam: Elsevier, 2017, vol. 150, 1 February 2017, p. 131-140. ISSN 0927-7765. Available from: https://dx.doi.org/10.1016/j.colsurfb.2016.11.023.
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Basic information
Original name 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
Authors HEGER, Zbynek (203 Czech Republic), Hana POLANSKÁ (203 Czech Republic, belonging to the institution), Sona KRIZKOVA (203 Czech Republic), Jan BALVAN (203 Czech Republic, belonging to the institution), Martina RAUDENSKÁ (203 Czech Republic, belonging to the institution), Simona DOSTALOVA (203 Czech Republic), Amitava MOULICK (203 Czech Republic), Michal MASAŘÍK (203 Czech Republic, guarantor, belonging to the institution) and Vojtech ADAM (203 Czech Republic).
Edition Colloids and Surfaces B: Biointerfaces, Amsterdam, Elsevier, 2017, 0927-7765.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 30105 Physiology
Country of publisher Netherlands
Confidentiality degree is not subject to a state or trade secret
Impact factor Impact factor: 3.997
RIV identification code RIV/00216224:14110/17:00095967
Organization unit Faculty of Medicine
Doi http://dx.doi.org/10.1016/j.colsurfb.2016.11.023
UT WoS 000393726900016
Keywords in English Drug delivery; Etoposide; In vitro release; Multi-walled carbon nanotubes; Nanomedicine
Tags EL OK
Tags International impact, Reviewed
Changed by Changed by: Soňa Böhmová, učo 232884. Changed: 15/3/2018 16:24.
Abstract
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.
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