Small Combinatorial Library of Lipidoids as Nanovectors for Gene Delivery

A small library of 27 lipidoids was set up by a combinatorial approach. These lipidoids were prepared from three polyamines and nine reactants with alkyl tail via epoxide ring-opening reaction or Michael addition. The polyamines include tris(2-aminoethyl)amine (TAEA), 1,4,7-triazacyclononane (TACN), and 1,4,7,10-tetraazacyclododecane (Cyclen), while the structures of nine reactants vary in both reacting groups and chain lengths. The lipidoids were obtained without any solvent and used directly without further purification, and no helper lipid was needed for the interaction with DNA. Initial screening by the EGFP transfection assay selected six lipidoid nanoparticles with good transfection efficiency for further investigation. Gel electrophoresis, TEM, and relative studies reveal that these lipidoids have good DNA condensation capability and the formed DNA complexes have good stability toward serum or nuclease. Quantitative transfection study with luciferase reporter gene showed that TACN-O14 could give 1....