2017
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, Zbynek; Hana POLANSKÁ; Sona KRIZKOVA; Jan BALVAN; Martina RAUDENSKÁ et. al.Základní údaje
Originální název
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
Autoři
HEGER, Zbynek; Hana POLANSKÁ; Sona KRIZKOVA; Jan BALVAN; Martina RAUDENSKÁ ORCID; Simona DOSTALOVA; Amitava MOULICK; Michal MASAŘÍK a Vojtech ADAM
Vydání
Colloids and Surfaces B: Biointerfaces, Amsterdam, Elsevier, 2017, 0927-7765
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
30105 Physiology
Stát vydavatele
Nizozemské království
Utajení
není předmětem státního či obchodního tajemství
Impakt faktor
Impact factor: 3.997
Kód RIV
RIV/00216224:14110/17:00095967
Organizační jednotka
Lékařská fakulta
UT WoS
000393726900016
EID Scopus
2-s2.0-84998881020
Klíčová slova anglicky
Drug delivery; Etoposide; In vitro release; Multi-walled carbon nanotubes; Nanomedicine
Štítky
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 15. 3. 2018 16:24, Soňa Böhmová
Anotace
V originále
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.