Kim You-Kyoung, Singh Bijay, Jiang Hu-Lin, Park Tae-Eun, Jiang Tao, Park In-Kyu, Cho Myung-Haing, Kang Sang-Kee, Choi Yun-Jaie, Cho Chong-Su
Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, South Korea; Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, South Korea; Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
Eur J Pharm Sci. 2014 Jan 23;51:165-72. doi: 10.1016/j.ejps.2013.09.011. Epub 2013 Sep 25.
Gene therapy is not successful due to lack of safe gene delivery vector, low transfection efficiency and inability to target the particular cells. Here, we synthesized a biocompatible block copolymer (abbreviated as PASPG) which consists of cationic poly[(aspartamide)(spermine)] for complexation with DNA and enhancing transfection efficiency due to buffering ability of spermine, poly(ethylene oxide)(PEO) for stability after systemic administration of the gene and N-acetylglucosamine (GlcNAc) as a specific ligand to target vimentin-expressing cells. Primarily, PASPG showed efficient complexation with DNA. Cell viability assay demonstrated that PASPG had low toxicity compared to polyethylenimine 25K. Furthermore, PASPG showed higher transfection efficiency in vimentin-expressing cells than vimentin-deficient ones due to the recognition of GlcNAc in the polymeric gene carrier by vimentin in the cells for the receptor-mediated endocytosis of PASPG. Favorably, the serum had no effect on transfection efficiency of PASPG due to the presence of hydrophilic PEO in the block copolymer. This study reveals that GlcNAc-coupled biocompatible block copolymer can specifically deliver gene to vimentin-expressing cells.
由于缺乏安全的基因递送载体、转染效率低以及无法靶向特定细胞，基因治疗并不成功。在此，我们合成了一种生物相容性嵌段共聚物（简称为PASPG），它由用于与DNA络合并因精胺的缓冲能力而提高转染效率的阳离子聚[（天冬酰胺）（精胺）]、用于基因全身给药后保持稳定性的聚环氧乙烷（PEO）以及作为靶向表达波形蛋白细胞的特异性配体的N-乙酰葡糖胺（GlcNAc）组成。首先，PASPG显示出与DNA的高效络合。细胞活力测定表明，与25K聚乙烯亚胺相比，PASPG具有较低的毒性。此外，由于细胞中的波形蛋白识别聚合物基因载体中的GlcNAc以实现PASPG的受体介导的内吞作用，PASPG在表达波形蛋白的细胞中显示出比波形蛋白缺陷细胞更高的转染效率。有利的是，由于嵌段共聚物中存在亲水性PEO，血清对PASPG的转染效率没有影响。这项研究表明，GlcNAc偶联的生物相容性嵌段共聚物可以特异性地将基因递送至表达波形蛋白的细胞。
