碘化丙啶
体外
化学
细胞凋亡
膜联蛋白
细胞毒性
流式细胞术
PEG比率
依托泊苷
癌细胞
细胞
分子生物学
聚乙烯亚胺
癌症研究
细胞培养
生物物理学
癌症
生物化学
生物
转染
程序性细胞死亡
化疗
经济
基因
遗传学
财务
作者
Zbyněk Heger,Hana Polanská,Soňa Křížková,Jan Balvan,Martina Raudenská,Simona Dostálová,Amitava Moulick,Michal Masařík,Vojtěch Adam
标识
DOI:10.1016/j.colsurfb.2016.11.023
摘要
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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