Gold nanoclusters-assisted delivery of NGF siRNA for effective treatment of pancreatic cancer.
Gold nanoclusters-assisted delivery of NGF siRNA for effective treatment of pancreatic cancer.
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金纳米簇辅助 NGF siRNA 递送有效治疗胰腺癌
DOI：
10.1038/ncomms15130
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发表时间：
2017-04-25
影响因子：
16.6
通讯作者：
Jiang X
中科院分区：
文献类型：
--
作者：
Lei Y;Tang L;Xie Y;Xianyu Y;Zhang L;Wang P;Hamada Y;Jiang K;Zheng W;Jiang X
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）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，金纳米团簇辅助递送NGF的siRNA（GNC-siRNA）允许有效的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，而无不良反应。我们的研究构成了一个简单但有效的方法来抑制胰腺癌通过NGF敲低，这表明了一个有前途的治疗方向胰腺癌。
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.