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 (203 Česká republika), Hana POLANSKÁ (203 Česká republika, domácí), Sona KRIZKOVA (203 Česká republika), Jan BALVAN (203 Česká republika, domácí), Martina RAUDENSKÁ (203 Česká republika, domácí), Simona DOSTALOVA (203 Česká republika), Amitava MOULICK (203 Česká republika), Michal MASAŘÍK (203 Česká republika, garant, domácí) a Vojtech ADAM (203 Česká republika)
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
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.