用于提高 siRNA 活性的羟氯喹偶联金纳米粒子。
Hydroxychloroquine-conjugated gold nanoparticles for improved siRNA activity.
机构信息
Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8856, Japan.
Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8856, Japan.
出版信息
Biomaterials. 2016 Jun;90:62-71. doi: 10.1016/j.biomaterials.2016.02.027. Epub 2016 Mar 5.
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.
目前的 siRNA 递送技术依赖于药物剂型将最大剂量的 siRNA 递送到肿瘤部位。然而，这种原理并没有解决控制沉默活性的细胞内瓶颈。在这里，我们测试了羟氯喹缀合对 siRNA 缀合聚乙二醇金纳米粒子的细胞内命运和沉默活性的影响。加入羟氯喹可改善内涵体逃逸，并增加 siRNA 引导链向 RNA 诱导沉默复合物 (RISC) 的分布，这是 siRNA 效力的两个关键障碍。这种修饰显著提高了细胞内的基因下调。总的来说，我们的数据表明这种修饰对于设计改良的 siRNA 递药系统具有益处。
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