Synthesis and Characterizations of New Lysine-Based Biodegradable Cationic Poly(urethane-co-ester) and Study on Self-Assembled Nanoparticles with DNA

To improve the self-assembly efficiency of nanoparticles with DNA, we synthesized lysine-based poly(urethane-co-ester) PMMD (6) and polyester PDMA (8) bearing ester linkages in the backbone and tertiary amines in the side chain. Both poly(urethane-co-ester) PMMD (6) and polyester PDMA (8), readily self-assembled with plasmid DNA (pCMV-beta-gal) in HEPES buffer, were characterized by dynamic light scattering and zeta-potential. The results reveal that PMMD (6) and PDMA (8) were able to self-assemble particles with DNA and yield complexes with positive charges of 80-115 nm and 170-180 nm in size at mass ratios (W/W) of 2/1 and 20/1, respectively. The degradation studies indicate that the half-life of PMMD (6) in the HEPES buffer was 20 h at pH 7.4. Titration studies were performed to determine the buffering capacities of the polymers. In addition, the COS-7 cell viabilities in the presence of PMMD/DNA, PDMA/DNA, and PEI/DNA were studied. The results indicate that PMMD (6) is an attractive cationic poly(urethane-co-ester) for gene delivery and an interesting candidate for further study.