期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 506, 期 1-2, 页码 268-279出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2016.04.031
关键词
Liposome-delivery; Cholesterol-delivery; Aptamer; eEF1A; HCC
资金
- Fondazione Cassa di Risparmio of Trieste
- Fondazione Benefica Kathleen Foreman Casali of Trieste
- Beneficentia Stiftung of Vaduz Liechtenstein
- Italian Minister of Instruction, University and Research (MIUR), PRIN [20109PLMH2]
- 5 per mille of Lega Italiana per la Lotta contro i Tumori (LILT), Italian Minister of Health
The high morbidity and mortality of hepatocellular carcinoma (HCC) is mostly due to the limited efficacy of the available therapeutic approaches. Here we explore the anti-HCC potential of an aptamer targeting the elongation factor 1A (eEF1A), a protein implicated in the promotion of HCC. As delivery methods, we have compared the effectiveness of cationic liposome and cholesterol-mediated approaches. A75 nucleotide long aptamer containing GT repetition (GT75) was tested in three HCC cell lines, HepG2, HuH7 and JHH6. When delivered by liposomes, GT75 was able to effectively reducing HCC cells viability in a dose and time dependent fashion. Particular sensitive were JHH6 where increased apoptosis with no effects on cell cycle were observed. GT75 effect was likely due to the interference with eEF1A activity as neither the mRNA nor the protein levels were significantly affected. Notably, cholesterol-mediated delivery of GT75 abrogated its efficacy due to cellular mis-localization as proven by fluorescence and confocal microscopic analysis. Finally, liposome-mediated delivery of GT75 improved the therapeutic index of the anticancer drugs bortezomib and idarubicin. In conclusion, liposome but not cholesterol-mediated delivery of GT75 resulted in an effective delivery of GT75, causing the impairment of the vitality of a panel of HCC derived cells. (c) 2016 Elsevier B.V. All rights reserved.
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