Hydroxychloroquine-conjugated gold nanoparticles for improved siRNA activity

被引:46
作者
Perche, F. [1 ,2 ,3 ]
Yi, Y. [1 ]
Hespel, L. [1 ]
Mi, P. [1 ]
Dirisala, A. [1 ]
Cabral, H. [1 ]
Miyata, K. [1 ]
Kataoka, K. [1 ]
机构
[1] Univ Tokyo, Grad Sch Engn, Dept Mat Engn, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138856, Japan
[2] CNRS, UPR4301, INSERM, Ctr Biophys Mol, F-45071 Orleans 02, France
[3] Univ Orleans, F-45071 Orleans 02, France
关键词
siRNA delivery; Hydroxychloroquine; Gold nanoparticles; Intracellular bioavailability; SMALL INTERFERING RNA; INTRACELLULAR DELIVERY; POLYMERIC MICELLES; DRUG-DELIVERY; GENE-TRANSFER; IDENTIFICATION; LOCALIZATION; AGGREGATION; TRAFFICKING; MECHANISM;
D O I
10.1016/j.biomaterials.2016.02.027
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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.
引用
收藏
页码:62 / 71
页数:10
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