Anionic amino acid-derived cationic lipid for siRNA delivery

Title
Anionic amino acid-derived cationic lipid for siRNA delivery
Authors
서민성심가영이한영한수은유용희최용석김광명권익찬원권연김영봉오유경
Keywords
cationic lipid; Liposome; siRNA; Gene reduction; Viability
Issue Date
2009-11
Publisher
Journal of controlled release : official journal of the Controlled Release Society
Citation
VOL 140, NO 3, 268-276
Abstract
Viable siRNA therapeutic strategies require the concurrent development of effective and safe delivery systems. Here, we described the synthesis of a new cationic lipid, N,N″-dioleylglutamide (DG), and evaluated DG-based liposomes as an siRNA delivery system. DG, an amino acid derivative, was synthesized by peptide bond linkage of oleylamine to each carboxylic acid group of glutamic acid. Gel retardation assays showed that DG-based cationic liposomes and siRNA began to form complexes from the N/P ratio of 1.8. The viability of A549, HeLa and WM266.4 cells was significantly higher after treatment with DG-based liposomes than with Lipofectamine 2000 and cationic 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol)- based liposomes. The DG-based cationic liposomes could effectively deliver a fluorescent model siRNA into A549, HeLa, and WM266.4 human cancer cell lines, showing at least 2-fold higher fluorescence mean intensity values than did Lipofectamine 2000. When survivin-specific siRNA was delivered to cells in lipoplexes, survivin mRNA levels were reduced by DG-based liposomes to the higher extent than Lipofectamine 2000 and DC-Chol-based liposomes. When red fluorescent protein (RFP)-expressing cells were treated with RFP-specific siRNA (siRFP), RFP expression significantly decreased in cells treated with DGbased liposomes. Molecular imaging revealed that intratumoral injection of siRFP and DG-based liposome complexes significantly reduced fluorescence in RFP-expressing tumor tissues in mice. These results suggest that DG-based cationic liposomes would be of value for cellular delivery and in vivo local delivery of siRNA.
URI
http://pubs.kist.re.kr/handle/201004/36440
ISSN
0168-3659
Appears in Collections:
KIST Publication > Article
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE