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α,β-Poly(l-aspartate-graft-PEI): A pseudo-branched PEI as a gene carrier with low toxicity and high transfection efficiency

✍ Scribed by Jia-Hui Yu; Ji-Shan Quan; Jin Huang; Cheng-Yun Wang; Bo Sun; Jae-Woon Nah; Myung-Haing Cho; Chong-Su Cho


Book ID
103999622
Publisher
Elsevier Science
Year
2009
Tongue
English
Weight
627 KB
Volume
5
Category
Article
ISSN
1742-7061

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✦ Synopsis


The aim of this research is to develop a novel branched polyethylenimine (PEI)-like polycation as a potential gene carrier with high gene transfection efficiency and low toxicity. In particular, a,b-poly(L-aspartate-graft-PEI) (Asp-g-PEI), a pseudo-branched PEI, was synthesized by the ring-opening reaction of poly(L-succinimide) (PSI) with low molecular weight branched PEI (LMW PEI, MW = 600 and 1200). Good plasmid condensation and protection ability of Asp-g-PEI were confirmed by agarose gel electrophoresis assay. Asp-g-PEI/DNA complexes showed high positive zeta potential, narrow size distribution, good dispersity and a compact spherical shape with size below 250 nm when the N/P ratio was above 5, suggesting that they can be endocytosed. Cytotoxicity of Asp-g-PEI/DNA complexes was rather lower than that of PEI25K/DNA complexes, especially at high N/P ratio. The most efficient gene transfection of Asp-g-PEI/DNA complexes was similar or a little higher than that of PEI25K in 293T, HeLa and HepG2 cell lines, while almost 4 and 6 times higher than that of parent PEI1200 and PEI600, respectively, in HeLa cell line; as the molecular weight of parent PEI in Asp-g-PEI was increased from 600 to 1200, the transfection efficiency showed a tendency to decrease. The mechanism of Asp-g-PEI-mediated gene transfection was attributed to the ''proton sponge effect" due to PEI in the copolymer.