Hashimoto Mayu, Morimoto Minoru, Saimoto Hiroyuki, Shigemasa Yoshihiro, Yanagie Hironobu, Eriguchi Masazumi, Sato Toshinori
Department of Biosciences and Informatics, Keio University, 3-14-1, Hiyoshi, Yokohama 223-8522, Japan.
Biotechnol Lett. 2006 Jun;28(11):815-21. doi: 10.1007/s10529-006-9006-x. Epub 2006 May 31.
Chitosan is a biodegradable and biocompatible polymer and is useful as a non-viral vector for gene delivery. In order to deliver pDNA/chitosan complex into macrophages expressing a mannose receptor, mannose-modified chitosan (man-chitosan) was employed. The cellular uptake of pDNA/man-chitosan complexes through mannose recognition was then observed. The pDNA/man-chitosan complexes showed no significant cytotoxicity in mouse peritoneal macrophages, while pDNA/man-PEI complexes showed strong cytotoxicity. The pDNA/man-chitosan complexes showed much higher transfection efficiency than pDNA/chitosan complexes in mouse peritoneal macrophages. Observation with a confocal laser microscope suggested differences in the cellular uptake mechanism between pDNA/chitosan complexes and pDNA/man-chitosan complexes. Mannose receptor-mediated gene transfer thus enhances the transfection efficiency of pDNA/chitosan complexes.
壳聚糖是一种可生物降解且具有生物相容性的聚合物，可用作基因递送的非病毒载体。为了将pDNA/壳聚糖复合物递送至表达甘露糖受体的巨噬细胞中，采用了甘露糖修饰的壳聚糖（甘露糖-壳聚糖）。随后观察到通过甘露糖识别对pDNA/甘露糖-壳聚糖复合物的细胞摄取。pDNA/甘露糖-壳聚糖复合物在小鼠腹腔巨噬细胞中未显示出明显的细胞毒性，而pDNA/甘露糖-聚乙烯亚胺复合物则显示出强烈的细胞毒性。在小鼠腹腔巨噬细胞中，pDNA/甘露糖-壳聚糖复合物比pDNA/壳聚糖复合物表现出更高的转染效率。共聚焦激光显微镜观察表明，pDNA/壳聚糖复合物和pDNA/甘露糖-壳聚糖复合物之间的细胞摄取机制存在差异。因此，甘露糖受体介导的基因转移提高了pDNA/壳聚糖复合物的转染效率。
