Institute of Pharmaceutics, Zhejiang University, 388 Yuhangtang Road, Hangzhou 310058, PR China.
Int J Pharm. 2010 Mar 15;387(1-2):286-94. doi: 10.1016/j.ijpharm.2009.12.033. Epub 2009 Dec 24.
PEI and chitosan are considered to be promising non-viral gene delivery vectors. To improve the transfection efficiency of chitosan, we linked chitosan with polyethylenimine (PEI, Mw=1.8 kDa) by 1,1'-carbonyldiimidazole to form a complex. The composition, particle size, as well as the zeta potential of this chitosan-linked-PEI (CP) complex were measured. And the DNA binding ability, cytotoxicity, and gene transfection efficiency of CP complex were also investigated in cancer cells. In HepG2, A549 and HeLa cells, CP complex exhibited lower cytotoxicity as compared with PEI25KDa (Mw=25 kDa), a positive control proved to be an efficient gene transfection polymer. Likewise, it showed good transfection efficiency in these cancer cell lines. Specifically, the long-term transfection efficiency of CP was higher than PEI25KDa as demonstrated by the in vitro cancer cell model. The confocal laser scanning microscopy data showed the time for CP to enter the nucleus was 4h, which was longer than that of PEI25KDa but shorter than that of chitosan. Furthermore, CP complexes were used as a gene carrier to deliver the CCL22 gene into H22 cells. When these gene-altered cells were inoculated in mice, the tumor growth rate was significantly decreased, indicating the CP copolymer was a promising vector for the therapeutic gene delivery.
PEI 和壳聚糖被认为是很有前途的非病毒基因传递载体。为了提高壳聚糖的转染效率，我们通过 1,1'-碳化二咪唑将壳聚糖与聚乙烯亚胺（PEI，Mw=1.8 kDa）连接起来，形成一种复合物。测量了这种壳聚糖连接的聚乙烯亚胺（CP）复合物的组成、粒径以及 ζ 电位。并在癌细胞中研究了 CP 复合物的 DNA 结合能力、细胞毒性和基因转染效率。在 HepG2、A549 和 HeLa 细胞中，CP 复合物的细胞毒性低于阳性对照物 PEI25KDa（Mw=25 kDa），被证明是一种有效的基因转染聚合物。同样，它在这些癌细胞系中表现出良好的转染效率。具体来说，通过体外癌细胞模型证明 CP 的长期转染效率高于 PEI25KDa。共聚焦激光扫描显微镜数据显示 CP 进入细胞核的时间为 4 小时，长于 PEI25KDa，但短于壳聚糖。此外，CP 复合物被用作基因载体将 CCL22 基因递送至 H22 细胞。当这些基因改变的细胞接种到小鼠中时，肿瘤生长速度明显降低，表明 CP 共聚物是一种有前途的治疗基因传递载体。
