Journal
BIOMATERIALS
Volume 90, Issue -, Pages 62-71Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2016.02.027
Keywords
siRNA delivery; Hydroxychloroquine; Gold nanoparticles; Intracellular bioavailability
Funding
- JSPS KAKENHI [14F04352]
- Grants-in-Aid for Scientific Research [14F04352, 15K12534, 25000006] Funding Source: KAKEN
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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.
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