α,β-Poly(l-aspartate-graft-PEI): A pseudo-branched PEI as a gene carrier with low toxicity and high transfection efficiency
2009; Elsevier BV; Volume: 5; Issue: 7 Linguagem: Inglês
10.1016/j.actbio.2009.03.012
ISSN1878-7568
AutoresJiahui Yu, Ji‐Shan Quan, Jin Huang, Chengyun Wang, Bo Sun, Jae‐Woon Nah, Myung‐Haing Cho, Chong‐Su Cho,
Tópico(s)Virus-based gene therapy research
ResumoThe 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, α,β-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.
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