Beijing Engineering Research Center for BioNanotechnology and CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, Beijing 100190, China.
Department of Nano-Medical Science, Graduate School of Medicine, Tohoku University, Sendai 980-8575, Japan.
Nat Commun. 2017 Apr 25;8:15130. doi: 10.1038/ncomms15130.
Pancreatic cancer is one of the deadliest human cancers, whose progression is highly dependent on the nervous microenvironment. The suppression of gene expression of nerve growth factor (NGF) may have great potential in pancreatic cancer treatment. Here we show that gold nanocluster-assisted delivery of siRNA of NGF (GNC-siRNA) allows efficient NGF gene silencing and pancreatic cancer treatment. The GNC-siRNA complex increases the stability of siRNA in serum, prolongs the circulation lifetime of siRNA in blood and enhances the cellular uptake and tumour accumulation of siRNA. The GNC-siRNA complex potently downregulates the NGF expression in Panc-1 cells and in pancreatic tumours, and effectively inhibits the tumour progression in three pancreatic tumour models (subcutaneous model, orthotopic model and patient-derived xenograft model) without adverse effects. Our study constitutes a straightforward but effective approach to inhibit pancreatic cancer via NGF knockdown, suggesting a promising therapeutic direction for pancreatic cancer.
胰腺癌是人类最致命的癌症之一，其进展高度依赖于神经微环境。抑制神经生长因子（NGF）的基因表达在胰腺癌治疗中可能具有巨大的潜力。在这里，我们表明，金纳米簇辅助递送 NGF 的 siRNA（GNC-siRNA）可以实现有效的 NGF 基因沉默和胰腺癌治疗。GNC-siRNA 复合物增加了 siRNA 在血清中的稳定性，延长了 siRNA 在血液中的循环寿命，并增强了 siRNA 的细胞摄取和肿瘤积累。GNC-siRNA 复合物可有效下调 Panc-1 细胞和胰腺肿瘤中的 NGF 表达，并有效抑制三种胰腺肿瘤模型（皮下模型、原位模型和患者来源的异种移植模型）中的肿瘤进展，没有不良反应。我们的研究构成了一种通过 NGF 敲低抑制胰腺癌的简单但有效的方法，为胰腺癌的治疗提供了一个有前途的方向。
