Gene transfer by DNA/mannosylated chitosan complexes into mouse peritoneal macrophages

Gene transfer by DNA/mannosylated chitosan complexes into mouse peritoneal macrophages
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DOI:
10.1007/s10529-006-9006-x
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发表时间:
2006-06-01
影响因子:
2.7
通讯作者:
Sato, Toshinori
Sato, Toshinori
中科院分区:
工程技术4区
文献类型:
--
作者:
Hashimoto, Mayu;Morimoto, Minoru;Sato, Toshinori

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壳聚糖是一种生物可降解和生物相容的聚合物,可用作基因递送的非病毒载体。为了将pDNA/壳聚糖复合物递送到表达甘露糖受体的巨噬细胞中,采用甘露糖修饰的壳聚糖(man-chitosan)。然后观察pDNA/man-壳聚糖复合物通过甘露糖识别的细胞摄取。pDNA/man-chitosan复合物对小鼠腹腔巨噬细胞无明显的细胞毒性,而pDNA/man-PEI复合物对小鼠腹腔巨噬细胞有较强的细胞毒性。pDNA/man-chitosan复合物对小鼠腹腔巨噬细胞的转染效率明显高于pDNA/chitosan复合物。激光共聚焦显微镜观察表明pDNA/壳聚糖复合物和pDNA/man-chitosan复合物的细胞摄取机制不同。甘露糖受体介导的基因转移因此增强了pDNA/壳聚糖复合物的转染效率。
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.