Document Detail


Lipid nanoparticles for hepatic delivery of small interfering RNA.
MedLine Citation:
PMID:  22652024     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
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
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-05-29
Journal Detail:
Title:  Biomaterials     Volume:  33     ISSN:  1878-5905     ISO Abbreviation:  Biomaterials     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-06-12     Completed Date:  2013-01-09     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  8100316     Medline TA:  Biomaterials     Country:  England    
Other Details:
Languages:  eng     Pagination:  5924-34     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Colloids
Down-Regulation
Drug Delivery Systems / methods*
Ethylenediamines / chemistry
Fatty Acids, Unsaturated / chemistry
Humans
Lipids / chemistry*
Liver / metabolism*
Liver Neoplasms / metabolism
Mice
Mice, Inbred ICR
Nanoparticles / chemistry*,  ultrastructure
RNA Stability
RNA, Small Interfering / administration & dosage*,  metabolism
Tissue Distribution
Grant Support
ID/Acronym/Agency:
R01DK088076/DK/NIDDK NIH HHS; R21 EB008247/EB/NIBIB NIH HHS; R21CA152969/CA/NCI NIH HHS; UL1 TR000090/TR/NCATS NIH HHS
Chemical
Reg. No./Substance:
0/Colloids; 0/Ethylenediamines; 0/Fatty Acids, Unsaturated; 0/Lipids; 0/RNA, Small Interfering; 4097-89-6/tris(2-aminoethyl)amine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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