Journal
BIOMATERIALS
Volume 29, Issue 1, Pages 15-22Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2007.08.048
Keywords
RNAi; THCO; multifunctional siRNA carrier; nanoparticles; surface modification
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In this study a multifunctional carrier (MFC), 1,4,7-triazanonylimino-bis[N-(oleicyl-cysteinyl-histinyl)-l-aminoethyl)propionamide] (THCO), containing protonatable amines of different pK(a)s, polymerizable cysteine residues and hydrophobic groups, was designed, synthesized and evaluated for efficient small interfering RNAs (siRNA) delivery. THCO showed pH-sensitive cellular membrane disruption at the endosomal-lysosomal pH to facilitate intracellular siRNA delivery. THCO formed stable and compact nanoparticles with siRNA through charge complexation, hydrophobic condensation and reversible polymerization. The THCO/siRNA nanoparticles were readily modified with PEG-Mal by reacting with remaining thiol groups at the surface. The siRNA delivery efficiency of THCO was comparable to that of Transfas (TM), much higher than that of N-(2,3-dioleoyloxy-l-propyl)trimethylammonium methyl sulphate (DOTAP) in serum-free medium. PEGylated THCO/siRNA nanoparticles resulted in higher transfection efficiency than those of Transfast (TM) and DOTAP in the presence of serum. This study demonstrated that the MFC-THCO is promising for efficient siRNA delivery. (c) 2007 Elsevier Ltd. All rights reserved.
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