School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
Carbohydr Polym. 2013 Sep 12;97(2):676-83. doi: 10.1016/j.carbpol.2013.05.036. Epub 2013 May 24.
In this study, N-phosphonium chitosans (NPCSs) with two degrees of substitution were synthesized in a homogeneous system as nonviral gene vectors. Grafted polymer/DNA complexes at various charge ratios were formulated and characterized. Particle sizes of NPCS/DNA complexes were between 110 and 160 nm as determined by dynamic light scattering. Accordingly, scanning electron microscopy photo of NPCS/DNA complexes exhibited a compact morphology. Zeta potentials of these complexes changed as the charge ratio and pH varied. The cytotoxicity assay showed that NPCS polymers were less toxic than branched PEI-25K. Furthermore, gene transfection efficiencies of NPCS/DNA complexes showed that the gene transfection ability of the grafted polymer was much better than chitosan and NPCS with the degree of substitution of 21.5% had comparative gene transfection efficiency to branched PEI-25K. Together, these results suggest that the low toxic NPCS grafted polymers could be used as effective gene delivery vectors.
在这项研究中，我们在均相体系中合成了两种取代度的 N-磷酰化壳聚糖（NPCSs）作为非病毒基因载体。我们制备并表征了不同电荷比的接枝聚合物/DNA 复合物。动态光散射法测定 NPCS/DNA 复合物的粒径在 110-160nm 之间。相应地，扫描电子显微镜照片显示 NPCS/DNA 复合物具有致密的形态。这些复合物的 Zeta 电位随电荷比和 pH 值的变化而变化。细胞毒性试验表明，NPCS 聚合物的毒性比支化 PEI-25K 低。此外，NPCS/DNA 复合物的基因转染效率表明，接枝聚合物的基因转染能力远优于壳聚糖，取代度为 21.5%的 NPCS 与支化 PEI-25K 的基因转染效率相当。综上所述，这些结果表明，低毒 NPCS 接枝聚合物可用作有效的基因传递载体。
