Self-Assembled Lipoplexes of Short Interfering RNA (siRNA) Using Spermine-Based Fatty Acid Amide Guanidines: Effect on Gene Silencing Efficiency

Author： Metwally Abdelkader A. Blagbrough Ian S.

Publisher： MDPI

E-ISSN： 1999-4923|3|3|406-424

ISSN： 1999-4923

Source： Pharmaceutics, Vol.3, Iss.3, 2011-07, pp. : 406-424

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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.