کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5394 | 372 | 2016 | 10 صفحه PDF | دانلود رایگان |
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.
We report hydroxychloroquine conjugation onto siRNA-functionalized PEGylated nanoparticles. Hydroxychloroquine modification enhanced endosomal escape, which improved RISC engagement of transfected siRNA and resulted in increased silencing activity over siRNA-functionalized PEGylated gold nanoparticles devoid of hydroxychloroquine.Figure optionsDownload high-quality image (213 K)Download as PowerPoint slide
Journal: Biomaterials - Volume 90, June 2016, Pages 62–71