Lipid Nanoparticles for Hepatic Delivery of Small Interfering RNA

Overview

Journal Biomaterials

Specialty Biomedical Engineering

Date 2012 Jun 2

PMID 22652024

Citations 17

Authors

Bo Yu

Shu-Hao Hsu

Chenguang Zhou

Xinmei Wang

Megan C Terp

Yun Wu

Lesheng Teng

Yicheng Mao

Feng Wang

Weiming Xue

Samson T Jacob

Kalpana Ghoshal

Robert J Lee

Ly J Lee

Affiliations

Soon will be listed here.

Abstract

Clinical application of small interfering RNA (siRNA) requires safe and efficient delivery in vivo. Here, we report the design and synthesis of lipid nanoparticles (LNPs) for siRNA delivery based on cationic lipids with multiple tertiary amines and hydrophobic linoleyl chains. LNPs incorporating the lipid containing tris(2-aminoethyl)amine (TREN) and 3 linoleyl chains, termed TRENL3, were found to have exceptionally high siRNA transfection efficacy that was markedly superior to lipofectamine, a commercial transfection agent. In addition, inclusion of polyunsaturated fatty acids, such as linoleic acid and linolenic acid in the formulation further enhanced the siRNA delivery efficiency. TRENL3 LNPs were further shown to transport siRNA into the cytosol primarily via macropinocytosis rather than clathrin-mediated endocytosis. The new LNPs have demonstrated preferential uptake by the liver and hepatocellular carcinoma in mice, thereby leading to high siRNA gene-silencing activity. These data suggest potential therapeutic applications of TRENL3 mediated delivery of siRNA for liver diseases.

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