An RGD-modified MRI-visible polymeric vector for targeted siRNA delivery to hepatocellular carcinoma in nude mice.
An RGD-modified MRI-visible polymeric vector for targeted siRNA delivery to hepatocellular carcinoma in nude mice.
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RGD 修饰的 MRI 可见聚合载体用于靶向 siRNA 递送至裸鼠肝细胞癌
DOI：
10.1371/journal.pone.0066416
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Shan H
中科院分区：
文献类型：
--
作者：
Wu C;Gong F;Pang P;Shen M;Zhu K;Cheng D;Liu Z;Shan H
RNA干扰（RNAi）在肝癌的基因治疗中具有重要的应用前景。靶向载体能够以高转染效率和稳定性将小干扰RNA（siRNA）递送到HCC细胞中。三肽精氨酸甘氨酸天冬氨酸（RGD）修饰的非病毒载体，聚乙二醇接枝的聚乙烯亚胺功能与超顺磁性氧化铁纳米粒子（RGD-PEG-g-PEI-SPION），构建作为磁共振成像（MRI）可见的纳米载体，用于交付生存素siRNA靶向人肝癌细胞系Bel-7402。进行RGD-PEG-g-PEI-SPION的生物物理表征。与非靶向递送系统相比，经RGD修饰的复合物在将Survivin siRNA转染至Bel-7402细胞中时表现出更高的转染效率，这导致在Survivin mRNA和蛋白表达水平上更显著的基因抑制。然后，caspase-3活化水平显著升高，并诱导显著水平的肿瘤细胞凋亡。结果，裸鼠Bel-7402肝癌模型中的肿瘤生长被显著抑制。RGD-PEG-g-PEI-SPION的靶向能力通过体外和体内进行的MRI扫描成功成像。我们的研究结果强烈表明，RGD-PEG-g-PEI-SPION可以潜在地用作靶向非病毒载体，用于改变肝细胞癌治疗中的基因表达，并作为有效的MRI探针用于体内检测肿瘤。
RNA interference (RNAi) has significant therapeutic promise for the genetic treatment of hepatocellular carcinoma (HCC). Targeted vectors are able to deliver small interfering RNA (siRNA) into HCC cells with high transfection efficiency and stability. The tripeptide arginine glycine aspartic acid (RGD)-modified non-viral vector, polyethylene glycol-grafted polyethylenimine functionalized with superparamagnetic iron oxide nanoparticles (RGD-PEG-g-PEI-SPION), was constructed as a magnetic resonance imaging (MRI)-visible nanocarrier for the delivery of Survivin siRNA targeting the human HCC cell line Bel-7402. The biophysical characterization of the RGD-PEG-g-PEI-SPION was performed. The RGD-modified complexes exhibited a higher transfection efficiency in transferring Survivin siRNA into Bel-7402 cells compared with a non-targeted delivery system, which resulted in more significant gene suppression at both the Survivin mRNA and protein expression levels. Then, the level of caspase-3 activation was significantly elevated, and a remarkable level of tumor cell apoptosis was induced. As a result, the tumor growth in the nude mice Bel-7402 hepatoma model was significantly inhibited. The targeting ability of the RGD-PEG-g-PEI-SPION was successfully imaged by MRI scans performed in vitro and in vivo. Our results strongly indicated that the RGD-PEG-g-PEI-SPION can potentially be used as a targeted non-viral vector for altering gene expression in the treatment of hepatocellular carcinoma and for detecting the tumor in vivo as an effective MRI probe.
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影响因子：
10.8
作者：
Merkel, Olivia M.;Librizzi, Damiano;Kissel, Thomas
通讯作者：
Kissel, Thomas
DOI：
10.1038/nrd2310
发表时间：
2007-06
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
de Fougerolles A;Vornlocher HP;Maraganore J;Lieberman J
通讯作者：
Lieberman J
一种 MRI 可见的非病毒载体，用于将 Bcl-2 siRNA 靶向递送至神经母细胞瘤。
影响因子：
8
作者：
Shen M;Gong F;Pang P;Zhu K;Meng X;Wu C;Wang J;Shan H;Shuai X
通讯作者：
Shuai X
影响因子：
10.8
作者：
Green, Jordan J.;Chiu, Eugene;Anderson, Daniel G.
通讯作者：
Anderson, Daniel G.
影响因子：
158.5
作者：
WEIDNER, N;SEMPLE, JP;FOLKMAN, J
通讯作者：
FOLKMAN, J