Cook Seung Eun, Park In Kyu, Kim Eun Mi, Jeong Hwan Jeong, Park Tae Gwan, Choi Yun Jaie, Akaike Toshihiro, Cho Chong Su
School of Agricultural Biotechnology, Seoul National University, Seoul 151-742, South Korea.
J Control Release. 2005 Jun 20;105(1-2):151-63. doi: 10.1016/j.jconrel.2005.03.011.
Polyethylenimine (PEI) has been used for the gene delivery system in vitro and in vivo since it has high transfection efficiency owing to proton buffer capacity. However, the use of PEI for gene delivery is limited due to cytotoxicity, non-specificity and unnecessary interaction with serum components. To overcome cytotoxicity and non-specificity, PEI was coupled with poly(vinyl pyrrolidone) (PVP) as the hydrophilic group to reduce cytotoxicity and lactose bearing galactose group for hepatocyte targeting. The galactosylated-PEI-graft-PVP (GPP) was complexed with DNA, and GPP/DNA complexes were characterized. GPP showed good DNA binding ability, high protection of DNA from nuclease attack. The sizes of DNA complexes show tendency to decrease with an increase of charge ratio and had a minimum value around 59 nm at the charge ratio of 40 for the GPP-1/DNA complex (PVP content: 4.1 mol%). The GPP showed low cytotoxicity. And GPP/DNA complexes were mediated by asialoglycoprotein receptors (ASGP-R)-mediated endocytosis. Also, the transfection efficiency of GPP-1/DNA complex at charge ratio of 40 in the HepG2 was higher than that of PEI/DNA one.
聚乙烯亚胺（PEI）因其质子缓冲能力而具有高转染效率，已被用于体外和体内基因递送系统。然而，由于细胞毒性、非特异性以及与血清成分的不必要相互作用，PEI在基因递送中的应用受到限制。为了克服细胞毒性和非特异性，将PEI与作为亲水基团的聚乙烯吡咯烷酮（PVP）偶联以降低细胞毒性，并与带有半乳糖基团的乳糖偶联用于肝细胞靶向。将半乳糖基化的PEI-接枝-PVP（GPP）与DNA复合，并对GPP/DNA复合物进行了表征。GPP表现出良好的DNA结合能力，对DNA具有高度的核酸酶攻击保护作用。DNA复合物的尺寸随电荷比的增加呈减小趋势，对于GPP-1/DNA复合物（PVP含量：4.1 mol%），在电荷比为40时具有最小值，约为59 nm。GPP表现出低细胞毒性。并且GPP/DNA复合物是通过去唾液酸糖蛋白受体（ASGP-R）介导的内吞作用介导的。此外，GPP-1/DNA复合物在电荷比为40时在HepG2细胞中的转染效率高于PEI/DNA复合物。
