A promising gene delivery system developed from PEGylated MoS2 nanosheets for gene therapy.

A promising gene delivery system developed from PEGylated MoS2 nanosheets for gene therapy.
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由聚乙二醇化 MoS2 纳米片开发的一种有前景的基因传递系统,用于基因治疗

DOI:
10.1186/1556-276x-9-587
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发表时间:
2014
影响因子:
--
通讯作者:
Guo L
Guo L
中科院分区:
材料科学3区
文献类型:
--
作者:
Kou Z;Wang X;Yuan R;Chen H;Zhi Q;Gao L;Wang B;Guo Z;Xue X;Cao W;Guo L

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MoS_2、MoSe_2、WS_2、WSe_2等新型二维纳米过渡金属化合物(TMDCs)具有优异的物理化学性质,近年来引起了不同领域的极大关注。在这里,我们首次利用MoS2作为一种新型的2D纳米载体用于基因传递和癌症治疗的巨大潜力。在我们的体系中,用硫辛酸修饰的聚乙二醇(LA-PEG)和支化的聚乙烯亚胺(PEI)合成了带正电荷的MoS_2-PEG-PEI。带正电的纳米材料的氨基末端可以与带负电的小干扰RNA(SiRNA)结合。检测纳米材料的物理化学特性后,采用四甲基偶氮唑蓝(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium)比色法评价其细胞毒性。Polo-like kinase1(PLK1)是一个已知的癌基因,在多个水平上是细胞周期传递的关键调节因子。用新型纳米载体携带的siRNA对PLK1进行基因敲除,采用定量聚合酶链式反应(QPCR)和Western印迹法检测干扰效率;用细胞凋亡实验检测PLK1的转染效果。结果表明,新型纳米载体具有良好的生物相容性,降低了细胞毒性,且携带基因的能力强,无血清干扰,在基因传递和治疗方面具有很大的潜力。
A new class of two-dimensional (2D) nanomaterial, transition metal dichalcogenides (TMDCs) such as MoS2, MoSe2, WS2, and WSe2 which have fantastic physical and chemical properties, has drawn tremendous attention in different fields recently. Herein, we for the first time take advantage of the great potential of MoS2 with well-engineered surface as a novel type of 2D nanocarriers for gene delivery and therapy of cancer. In our system, positively charged MoS2-PEG-PEI is synthesized with lipoic acid-modified polyethylene glycol (LA-PEG) and branched polyethylenimine (PEI). The amino end of positively charged nanomaterials can bind to the negatively charged small interfering RNA (siRNA). After detection of physical and chemical characteristics of the nanomaterial, cell toxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Polo-like kinase 1 (PLK1) was investigated as a well-known oncogene, which was a critical regulator of cell cycle transmission at multiple levels. Through knockdown of PLK1 with siRNA carried by novel nanovector, qPCR and Western blot were used to measure the interfering efficiency; apoptosis assay was used to detect the transfection effect of PLK1. All results showed that the novel nanocarrier revealed good biocompatibility, reduced cytotoxicity, as well as high gene-carrying ability without serum interference, thus would have great potential for gene delivery and therapy.