Self-Assembled Lipoplexes of Short Interfering RNA (siRNA) Using Spermine-Based Fatty Acid Amide Guanidines Effect on Gene Silencing Efficiency 英文参考文献.docVIP
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Self-Assembled Lipoplexes of Short Interfering RNA (siRNA) Using Spermine-Based Fatty Acid Amide Guanidines Effect on Gene Silencing Efficiency 英文参考文献
Pharmaceutics 2011, 3, 406-424; doi:10.3390/pharmaceutics3030406
OPEN ACCESS
pharmaceutics
ISSN 1999-4923
/journal/pharmaceutics
Article
Self-Assembled Lipoplexes of Short Interfering RNA (siRNA)
Using Spermine-Based Fatty Acid Amide Guanidines: Effect on
Gene Silencing Efficiency
Abdelkader A. Metwally and Ian S. Blagbrough *
Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK
? Author to whom correspondence should be addressed; E-Mail: prsisb@bath.ac.uk;
Tel.: +44-1225-386795; Fax: +44-1225-386114.
Received: 13 May 2011; in revised form: 20 June 2011 / Accepted: 5 July 2011 /
Published: 13 July 2011
Abstract: Four guanidine derivatives of N4,N9-diacylated spermine have been designed,
synthesized, and characterized. These guanidine-containing cationic lipids bound siRNA
and formed nanoparticles. Two cationic lipids with C18 unsaturated chains, N1,N12-
diamidino-N4,N9-dioleoylspermine and N1,N12-diamidino-N4-linoleoyl-N9-oleoylspermine,
were more efficient in terms of GFP expression reduction compared to the other cationic
lipids with shorter C12 (12:0) and very long C22 (22:1) chains. N1,N12-Diamidino-N4-
linoleoyl-N9-oleoylspermine siRNA lipoplexes resulted in GFP reduction (26%) in the
presence of serum, and cell viability (64%). These data are comparable to those obtained
with TransIT TKO. Thus, cationic lipid guanidines based on N4,N9-diacylated spermines
are good candidates for non-viral delivery of siRNA to HeLa cells using self-assembled
lipoplexes.
Keywords: fatty acids; gene silencing; GFP; guanidine; lipoplexes; nanoparticles; self-
assembly; siRNA; spermine
Pharmaceutics 2011, 3
407
1. Introduction
Short interfering RNA (siRNA) is a synthetic double-stranded (ds) RNA of 21-25 nucleotides per
strand. Post-transcriptional gene silencing by siRNA is an important biological tool in functional
genomic studies. Sequence specific gene
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