Hydroxychloroquine-conjugated gold nanoparticles for improved siRNA activity

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• 作者：F. Perche¹ ; Y. Yi ; L. Hespel ; P. Mi ; A. Dirisala ; H. Cabral ; K. Miyata ; K. Kataoka ; ^{kataoka@bmw.t.u-tokyo.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：siRNA delivery ; Hydroxychloroquine ; Gold nanoparticles ; Intracellular bioavailability
• 刊名：Biomaterials
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：90
• 期：Complete
• 页码：62-71
• 全文大小：1673 K

文摘

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.