Silencing of miR-21 by locked nucleic acid-lipid nanocapsule complexes sensitize human glioblastoma cells to radiation-induced cell death
Silencing of miR-21 by locked nucleic acid-lipid nanocapsule complexes sensitize human glioblastoma cells to radiation-induced cell death
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DOI：
10.1016/j.ijpharm.2013.05.049
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发表时间：
2013-10-01
影响因子：
5.8
通讯作者：
Garcion, E.
中科院分区：
文献类型：
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作者：
Griveau, A.;Bejaud, J.;Garcion, E.
最近发现的microRNA(MiRNA)作为主要的转录后抑制物，促使人们开发新的方法来靶向miRNA途径，以改善治疗。在这种背景下，尽管它们广泛临床应用的最大障碍仍然是传递，但与miRNA特异性和不可逆转地结合的核酸酶抗性锁定核酸(LNA)是有趣的武器。因此，本研究的目的是通过研究肿瘤基因miR-21miRNA参与肿瘤细胞对凋亡信号的抵抗，探讨在U87 MG胶质母细胞瘤(GBM)细胞中通过连接脂类纳米囊(LNC)的LNA作为miRNA靶向纳米药物沉默miRNA的可能性。在合成了用于核酸的两亲性脂肽仿射后，在LNC相转化配方过程中的插入后程序允许构建多肽偶联的LNC。然后，将多肽结合的LNC与LNAs孵育，以形成凝胶延迟分析和物理化学性质表征的复合体。RT-PCR检测，LNA-LNC复合体处理U87 MG细胞后，miR-21的表达明显降低。此外，U87 MG细胞暴露在LNA-LNC复合体中，然后进行外束照射，显示出细胞对治疗的敏感性显著提高，并强调了进一步研究这一miRNA靶向策略的兴趣。(C)2013爱思唯尔B.V.保留所有权利。
The recent discovery of microRNA (miRNA) as major post-transcriptional repressors prompt the interest of developing novel approaches to target miRNA pathways to improve therapy. In this context, although the most significant barrier to their widespread clinical use remains delivery, nuclease-resistant locked nucleic acid (LNA) that bind specifically and irreversibly to miRNA represent interesting weapons. Thus, by focusing on oncongenic miR-21 miRNA, which participate to cancer cell resistance to apoptotic signals, the aim of the present study was to investigate the possibility of silencing miRNA by LNA conjugated to lipid nanocapsules (LNCs) as miRNA-targeted nanomedicines in U87MG glioblastoma (GBM) cells. After synthesis of an amphiphilic lipopeptide affine for nucleic acids, a post-insertion procedure during the LNC phase inversion formulation process allowed to construct peptide-conjugated LNCs. Peptide-conjugated LNCs were then incubated with LNAs to allow the formation of complexes characterized in gel retardation assays and by their physicochemical properties. U87MG cell treatment by LNA-LNC complexes resulted in a marked reduction of miR-21 expression as assessed by RTqPCR. In addition, exposure of U87MG cells to LNA-LNC complexes followed by external beam radiation demonstrated a significant improvement of cell sensitivity to treatment and emphasizes the interest to investigate further this miRNA-targeted strategy. (C) 2013 Elsevier B. V. All rights reserved.