To understand the dual influence of multifold charge groups and conjugation of imidazole moiety on the physicochemical characteristics and the transfection activity of polymer complexes, a series of cationic polyphosphazenes based on poly(2-(2-aminoethyoxy)ethoxy) phosphazene (PAEP) with different components of multifold charge groups was synthesized by means of introducing imidazole-4-carboxaldehyde (IC) into PAEP through the formation of Schiff base. Though the polymers with primary amino groups (1 degree) alone or with abundant primary amino groups could bind DNA more efficiently than the ones with mainly or totally secondary (2 degrees) and tertiary (3 degrees) amino groups, all of the polymers could condense DNA into small particles within 100nm at the N/P ratio of 24. The cell viability of complexes and the pH buffering capacity of polymers increased with substitution degree of IC increasing. Among all the PAEP-based polymers, the highest transfection activity was found for poly(2-(2-aminoethyoxy)ethoxy/IC)phosphazene (PAEIC) 18 complexes containing 1 degree, 2 degrees and 3 degrees amines at a ratio of 3.5:1:1 with 18% substitution degree of IC, which indicated that either the coexistence of 1 degree, 2 degrees and 3 degrees amines or the conjugation of imidazole moiety played an important role in transfection activity. These results suggested that the most efficient gene carrier could be these polymers with 1 degree, 2 degrees and 3 degrees amines at an appropriate ratio, together with the presence of imidazole moiety in a small fraction.
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