A Gold Nanoparticle Platform for the Delivery of Functional TGF-beta 1 siRNA Into Cancer Cells
A Gold Nanoparticle Platform for the Delivery of Functional TGF-beta 1 siRNA Into Cancer Cells
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用于将功能性 TGF-β1 siRNA 递送至癌细胞的金纳米颗粒平台
DOI：
10.1166/jbn.2016.2217
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发表时间：
2016
影响因子：
2.9
通讯作者：
Zhang Yaqin
中科院分区：
文献类型：
--
作者：
Wu Jindao;Liu Bin;Wu Heming;Wu Younong;Zhang Wei;Zhao Shouwei;Zhang Long;Pan Xiongxiong;Gao Wen;Wang Xuehao;Yuan Yi;Zhang Yaqin
纳米颗粒，特别是金纳米颗粒（AuNPs），已被证明是将小RNA递送到癌细胞中的有效载体。在本研究中，我们使用半胱胺功能化的金纳米颗粒有效地将TGF-β1 siRNA导入肝癌HepG 2细胞的体外和体内。我们发现，与金纳米粒子介导的NC siRNA（AuNP-siNC）相比，金纳米粒子介导的TGF-β1 siRNA（AuNP-siTGFβ1）能有效地降低受体肿瘤细胞TGF-β1的水平，促进细胞凋亡，并显著抑制受体肿瘤细胞的增殖。将AuNP-siTGFβ1复合物全身给予人HepG 2异种移植小鼠同样降低了TGF-β1表达和下游TGF-β1信号传导。在功能上，AuNP-siTGFβ1强烈抑制肿瘤生长，与对照组相比，提高了荷瘤小鼠的存活率。总之，我们的结果表明，这里描述的具有AuNP的siRNA递送系统似乎是将RNAi治疗剂递送到肿瘤细胞中用于肿瘤治疗的高度有效的方法。
Nanoparticles, especially gold nanoparticles (AuNPs), have been shown to be an efficient carrier to deliver small RNAs into cancer cells. In this study, we used cysteamine-functionalized AuNPs to effectively deliver TGF-β1 siRNA into hepatoma HepG2 cells in vitro and in vivo. We found that, compared with AuNPs-mediated NC siRNA (AuNP-siNC), AuNPs-delivered TGF-β1 siRNA (AuNP-siTGFβ1) efficiently decreased the level of TGF-β1, increased cell apoptosis, and significantly inhibited the proliferation of recipient tumour cells. Systemic administration of the AuNP-siTGFβ1 complexes into human HepG2 xenografted mice likewise reduced TGF-β1 expression and downstream TGF-β1 signalling. Functionally, AuNP-siTGFβ1 strongly inhibited tumour growth and improved the survival rate of tumour-bearing mice compared with the control groups. In conclusion, our results demonstrate that the siRNA delivery system with AuNP described here appears to be a highly effective method to deliver RNAi therapeutics into tumour cells for oncotherapy.