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首页> 外文期刊>Nanotechnology >RNAi-based therapeutic nanostrategy: IL-8 gene silencing in pancreatic cancer cells using gold nanorods delivery vehicles
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RNAi-based therapeutic nanostrategy: IL-8 gene silencing in pancreatic cancer cells using gold nanorods delivery vehicles

机译：基于RNAi的治疗性纳米策略：使用金纳米棒递送载体使胰腺癌细胞中的IL-8基因沉默

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RNA interference (RNAi)-based gene silencing possesses great ability for therapeutic intervention in pancreatic cancer. Among various oncogene mutations, Interleukin-8 (IL-8) gene mutations are found to be overexpressed in many pancreatic cell lines. In this work, we demonstrate IL-8 gene silencing by employing an RNAi-based gene therapy approach and this is achieved by using gold nanorods (AuNRs) for efficient delivery of IL-8 small interfering RNA (siRNA) to the pancreatic cell lines of MiaPaCa-2 and Panc-1. Upon comparing to Panc-1 cells, we found that the dominant expression of the IL-8 gene in MiaPaCa-2 cells resulted in an aggressive behavior towards the processes of cell invasion and metastasis. We have hence investigated the suitability of using AuNRs as novel non-viral nanocarriers for the efficient uptake and delivery of IL-8 siRNA in realizing gene knockdown of both MiaPaCa-2 and Panc-1 cells. Flow cytometry and fluorescence imaging techniques have been applied to confirm transfection and release of IL-8 siRNA. The ratio of AuNRs and siRNA has been optimized and transfection efficiencies as high as 88.40 +/- 2.14% have been achieved. Upon successful delivery of IL-8 siRNA into cancer cells, the effects of IL-8 gene knockdown are quantified in terms of gene expression, cell invasion, cell migration and cell apoptosis assays. Statistical comparative studies for both MiaPaCa-2 and Panc-1 cells are presented in this work. IL-8 gene silencing has been demonstrated with knockdown efficiencies of 81.02 +/- 10.14% and 75.73 +/- 6.41% in MiaPaCa-2 and Panc-1 cells, respectively. Our results are then compared with a commercial transfection reagent, Oligofectamine, serving as positive control. The gene knockdown results illustrate the potential role of AuNRs as non-viral gene delivery vehicles for RNAi-based targeted cancer therapy applications.
机译：基于RNA干扰（RNAi）的基因沉默在胰腺癌的治疗干预方面具有强大的能力。在各种癌基因突变中，发现白介素8（IL-8）基因突变在许多胰腺细胞系中过表达。在这项工作中，我们通过采用基于RNAi的基因治疗方法论证了IL-8基因的沉默，这是通过使用金纳米棒（AuNRs）将IL-8小干扰RNA（siRNA）有效递送至胰腺细胞系而实现的。 MiaPaCa-2和Panc-1。通过与Panc-1细胞进行比较，我们发现MiaPaCa-2细胞中IL-8基因的显性表达导致了对细胞侵袭和转移过程的攻击行为。因此，我们已经研究了使用AuNRs作为新型非病毒纳米载体在实现MiaPaCa-2和Panc-1细胞基因敲低中有效吸收和输送IL-8 siRNA的适用性。流式细胞仪和荧光成像技术已用于确认IL-8 siRNA的转染和释放。 AuNRs和siRNA的比例已经过优化，转染效率高达88.40 +/- 2.14％。将IL-8 siRNA成功传递到癌细胞中后，可根据基因表达，细胞侵袭，细胞迁移和细胞凋亡分析量化IL-8基因敲低的影响。这项工作介绍了MiaPaCa-2和Panc-1细胞的统计比较研究。已经证明，在MiaPaCa-2和Panc-1细胞中，IL-8基因沉默的击倒效率分别为81.02 +/- 10.14％和75.73 +/- 6.41％。然后将我们的结果与作为阳性对照的商业转染试剂Oligofectamine进行比较。基因敲低的结果说明了AuNRs作为基于RNAi的靶向癌症治疗应用的非病毒基因递送载体的潜在作用。

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