title: Biophysical properties and supramolecular structure of self-assembled liposome/ε-peptide/DNA nanoparticles: correlation with gene delivery.
abstract: Using solid-phase synthesis, lysine can be oligomerized by a reaction of the peptide carboxylate with the ε-amino group to produce nontoxic, biodegradable cationic peptides, ε-oligo(L-lysines). Here α-substituted derivatives of such ε-oligo(L-lysines) containing arginine and histidine in the side chain were tested as vectors for in vitro gene delivery. Combination of ε-oligolysines with the cationic lipid DOTAP and plasmid DNA resulted in transfection efficiency exceeding that of DOTAP alone, without significant increase in cytotoxicity. Synchrotron small-angle X-ray scattering studies revealed self-assembly of the DOTAP, ε-oligolysines, and DNA to ordered lamellar complexes. High transfection efficiency of the nanoparticles correlates with increase in zeta potential above +20 mV and requires particle size to be below 500 nm. The synergistic effect of branched ε-oligolysines and DOTAP in gene delivery can be explained by the increase in surface charge and by the supramolecular structure of the DOTAP/ε-oligolysine/DNA nanoparticles.
authors: School of Biological Sciences, Nanyang Technological University, Singapore, 637551.
authors: Jiang
authors: J
authors: Yan
authors: Nikolay
authors: N
authors: Korolev
authors: Khee Dong
authors: KD
authors: Eom
authors: James P
authors: JP
authors: Tam
authors: Lars
authors: L
authors: Nordenskiöld
mesh_terms: D004247:DNA / Q000737:chemistry* / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes / Q000737:chemistry* / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry*; D010957:Plasmids / Q000737:chemistry* / Q000494:pharmacology; D011107:Polylysine / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000737:chemistry* / Q000494:pharmacology; D014162:Transfection / Q000379:methods*
chemical_list: D005229:Fatty Acids, Monounsaturated; D008081:Liposomes; D000644:Quaternary Ammonium Compounds; D011107:Polylysine; D004247:DNA; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane