Molecular Imaging Lab, Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
PLoS One. 2013 Jun 7;8(6):e66416. doi: 10.1371/journal.pone.0066416. Print 2013.
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.
RNA 干扰（RNAi）在肝细胞癌（HCC）的基因治疗方面具有重要的治疗前景。靶向载体能够将小干扰 RNA（siRNA）高效稳定地递送至 HCC 细胞。三肽精氨酸甘氨酸天冬氨酸（RGD）修饰的非病毒载体，聚乙二醇接枝的超顺磁性氧化铁纳米粒子功能化的聚乙烯亚胺（RGD-PEG-g-PEI-SPION），被构建为一种磁共振成像（MRI）可见的纳米载体，用于递送针对人 HCC 细胞系 Bel-7402 的 Survivin siRNA。对 RGD-PEG-g-PEI-SPION 的生物物理特性进行了表征。与非靶向递送系统相比，RGD 修饰的复合物在将 Survivin siRNA 转染入 Bel-7402 细胞中表现出更高的转染效率，从而导致 Survivin mRNA 和蛋白表达水平的基因抑制更为显著。然后，caspase-3 的激活水平显著升高，诱导了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受到显著抑制。通过体外和体内 MRI 扫描成功地对 RGD-PEG-g-PEI-SPION 的靶向能力进行了成像。我们的研究结果强烈表明，RGD-PEG-g-PEI-SPION 可作为一种潜在的靶向非病毒载体，用于改变肝细胞癌的基因表达，并作为有效的 MRI 探针在体内检测肿瘤。
