Qiao Jingbo, Hong Tu, Triana Taylor S, Guo Honglian, Chung Dai H, Xu Ya-Qiong
Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN 37232.
Department of Electrical Engineering and Computer Science, Vanderbilt University, Nashville, TN 37235.
RSC Adv. 2013 Apr 14;3(14):4544-4551. doi: 10.1039/C3RA23023F.
We demonstrate a newly-developed magneto-fluorescent carbon nanotube (CNT) mediated siRNA (CNT-siRNA) delivery system, which significantly silences our target of interest, gastrin-releasing peptide receptor (GRP-R), in neuroblastoma. CNT-siGRP-R resulted in a 50% silencing efficiency and a sustained efficacy of 9 days for one-time siRNA treatment , whereas siRNA delivered by the commercial transfection reagent couldn't knockdown GRP-R expression. We further show that CNT-siRNA efficiently inhibits the growth of subcutaneous xenograft tumors . This system allows us to track the CNT-siRNA distribution via both near-infrared fluorescence and magnetic resonance imaging. Moreover, our delivery system can be used to knockdown GRP-R expression in other cancer cell types, such as human breast cancer cells. The high efficiency and sustained efficacy may indicate that the natural stacking interactions between CNTs and siRNAs can protect siRNAs from degradation and enhance their stability during the delivery process.
我们展示了一种新开发的磁荧光碳纳米管(CNT)介导的小干扰RNA(siRNA)递送系统,该系统能显著沉默神经母细胞瘤中我们感兴趣的靶标——胃泌素释放肽受体(GRP-R)。CNT-siGRP-R单次siRNA处理导致50%的沉默效率和9天的持续效果,而商业转染试剂递送的siRNA无法敲低GRP-R表达。我们进一步表明,CNT-siRNA能有效抑制皮下异种移植肿瘤的生长。该系统使我们能够通过近红外荧光和磁共振成像追踪CNT-siRNA的分布。此外,我们的递送系统可用于敲低其他癌细胞类型(如人乳腺癌细胞)中的GRP-R表达。高效率和持续效果可能表明CNT与siRNA之间的自然堆积相互作用可保护siRNA不被降解,并在递送过程中增强其稳定性。