Poly(amido amine) is an ideal carrier of miR-7 for enhancing gene silencing effects on the EGFR pathway in U251 glioma cells

Poly(amido amine) is an ideal carrier of miR-7 for enhancing gene silencing effects on the EGFR pathway in U251 glioma cells
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聚酰胺基胺是 miR-7 的理想载体,可增强 U251 胶质瘤细胞中 EGFR 通路的基因沉默作用

DOI:
10.3892/or.2013.2283
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发表时间:
2013-04-01
期刊:
影响因子:
4.2
通讯作者:
Liu, Zhenlin
Liu, Zhenlin
中科院分区:
医学3区
文献类型:
--
作者:
Liu, Xiaozhi;Li, Gang;Liu, Zhenlin

文献摘要

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MicroRNAs被认为是胶质瘤基因治疗的有前途的药物。然而,传统的给药途径,如口服和静脉输注,由于血脑屏障和细胞间滞留,效率较低,从而限制了它们的应用。近年来的研究表明,聚酰胺胺(PAMAM)具有高增溶、缓释、低毒等优点,是一种候选载体。本研究以PAMAM为载体,将miR-7基因导入U251人脑胶质瘤细胞,检测其体内、外的转染率和治疗效果。我们发现,与脂质体相比,PAMAM具有更高的转染率和更长的作用时间,miR-7有效地沉默了一些参与表皮生长因子受体(EGFR)途径的基因,在体内和体外治疗脑胶质瘤取得了良好的效果。这些研究为开发高效的小分子药物载体奠定了基础。
microRNAs are regarded as promising drugs for glioma gene therapy. However, conventional administration routes, such as oral administration and intravenous infusion, present low efficiency due to the blood-brain barrier and intercellular retention, thereby limiting their application. Recent studies showed poly(amido amine) (PAMAM) was a candidate carrier due to its high solubilization, delayed release and low toxicity. In the present study, U251 human brain glioma cells were transfected with the miR-7 gene using PAMAM as the vector to determine the transfection efficiency and therapeutic effects in vivo and in vitro. We found that PAMAM exhibited higher transfection efficiency and longer duration of action compared with liposome delivery, and miR-7 efficiently silenced some genes involved in the epidermal growth factor receptor (EGFR) pathway and achieved favorable effects in treating glioma in vivo and in vitro. These investigations provide a basis for developing high-efficiency micromolecular drug delivery.