Galactosylated Lipidoid Nanoparticles for Delivery of Small Interfering RNA to Inhibit Hepatitis C Viral Replication In Vivo

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Small interfering RNA (siRNA) delivery can provide an effective therapy for treating viral diseases by silencing genes involved in viral replication. In this study, a liver-targeting formulation of lipidoid nanoparticle for delivery of siRNA that targets protein kinase C-related kinase 2 (PRK2) to inhibit hepatitis C virus (HCV) replication is reported. The most effective, minimally cytotoxic lipidoid for siRNA delivery to hepatic cells is identified from a small library of alkyl epoxide-polyamine conjugates. In vitro transfection of PRK2 siRNA (siPRK2) using this lipidoid induces significant silencing of PRK2 (approximate to 80%), suppressing HCV replication in human hepatic cells transfected with the HCV subgenomic replicon. Systemic administration of siPRK2 using the lipidoid nanoparticles results in significant reduction of host PRK2 in the mouse liver (approximate to 60%). This treatment significantly suppresses HCV replication in an HCV-xenograft mouse model. siRNA delivery to the liver is further improved via galactosylation of the lipidoid. Compared with the unmodified lipidoid formulation, galactosylated lipidoids induce greater silencing of host PRK2 in mouse livers (approximate to 80%) and more rapid suppression of HCV replication in an HCV-xenograft mouse. This study suggests that galactosylated lipidoid nanoparticles could provide a treatment for hepatitis C by mediating delivery of anti-viral RNA interference therapeutics to the liver.
Publisher
WILEY-BLACKWELL
Issue Date
2016-11
Language
English
Article Type
Article
Keywords

ENHANCED CELLULAR UPTAKE; SIRNA DELIVERY; PROTEIN-KINASE; GENE DELIVERY; ALTERED PHARMACOKINETICS; COMBINATORIAL LIBRARY; TARGETED DELIVERY; VIRUS-REPLICATION; SYSTEMIC DELIVERY; CANCER-CELLS

Citation

ADVANCED HEALTHCARE MATERIALS, v.5, no.22, pp.2931 - 2941

ISSN
2192-2640
DOI
10.1002/adhm.201600416
URI
http://hdl.handle.net/10203/219641
Appears in Collection
CH-Journal Papers(저널논문)
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