Hydroxychloroquine-conjugated gold nanoparticles for improved siRNA activity
Hydroxychloroquine-conjugated gold nanoparticles for improved siRNA activity
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DOI：
10.1016/j.biomaterials.2016.02.027
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发表时间：
2016-06-01
期刊：
影响因子：
14
通讯作者：
Kataoka, K.
中科院分区：
文献类型：
--
作者：
Perche, F.;Yi, Y.;Kataoka, K.
目前的 siRNA 递送技术依赖于药物剂型将最大剂量的 siRNA 递送至肿瘤。然而，这个基本原理并没有解决控制沉默活动的细胞内瓶颈。在这里，我们测试了羟氯喹缀合对 siRNA 缀合的聚乙二醇化金纳米粒子的细胞内命运和沉默活性的影响。添加羟氯喹可改善内体逃逸并增加 siRNA 引导链在 RNA 诱导沉默复合物 (RISC) 中的分布，这两个因素都是 siRNA 效力的关键障碍。这种修饰显着改善了cellulo中的基因下调。总而言之，我们的数据表明这种修饰对于改进 siRNA 递送系统的设计有好处。 (C) 2016 Elsevier Ltd. 保留所有权利。
Current technology of siRNA delivery relies on pharmaceutical dosage forms to route maximal doses of siRNA to the tumor. However, this rationale does not address intracellular bottlenecks governing silencing activity. Here, we tested the impact of hydroxychloroquine conjugation on the intracellular fate and silencing activity of siRNA conjugated PEGylated gold nanoparticles. Addition of hydroxychloroquine improved endosomal escape and increased siRNA guide strand distribution to the RNA induced silencing complex (RISC), both crucial obstacles to the potency of siRNA. This modification significantly improved gene downregulation in cellulo. Altogether, our data suggest the benefit of this modification for the design of improved siRNA delivery systems. (C) 2016 Elsevier Ltd. All rights reserved.