Effect of cationic charge on receptor-mediated transfection using mannosylated cationic liposome/plasmid DNA complexes following the intravenous administration in mice.
Effect of cationic charge on receptor-mediated transfection using mannosylated cationic liposome/plasmid DNA complexes following the intravenous administration in mice.
复制标题
小鼠静脉内给药后，使用甘露糖化阳离子脂质体/质粒 DNA 复合物，阳离子电荷对受体介导的转染的影响。
作者：
S. Kawakami;Y. Hattori;Y. Lu;Y. Higuchi;F. Yamashita;M. Hashida
本研究的目的是评价在小鼠中静脉内给予含有顺丁烯-5-基氧基-N-[4-[（1-亚氨基-2-D-硫甘露糖基-乙基）氨基]丁基]甲酰胺（Man-C4-Chol）的阳离子脂质体/pDNA复合物后复合物的阳离子电荷的影响。在细胞表面表达甘露糖受体的肝和脾中，以1.0：2.3和/或1.0：3.1的电荷比（-：+）静脉内施用复合物后的转染效率高于肺中的转染效率。另一方面，当以1.0：4.7的电荷比（-：+）形成复合物时，肺中的转染效率最高，表明非特异性相互作用。尽管脱唾液酸糖蛋白受体在肝细胞上表达，但通过静脉内施用与异戊烯-5-基氧基-N-[4-[（1-亚氨基-2-D-硫代半乳糖基-乙基）-氨基]丁基]甲酰胺（Gal-C4-Chol）/DOPE脂质体复合的pDNA（电荷比（-：+）为1.0：2.3），不能实现肝选择性基因转染。该信息支持用于静脉内施用后细胞特异性基因递送的pDNA/配体接枝的阳离子脂质体复合物的设计。
The purpose of this study was to evaluate the effect of cationic charge of complexes after intravenous administration of cholesten-5-yloxy-N-[4-[(1-imino-2-D-thiomannosyl-ethyl)amino]butyl]formamide (Man-C4-Chol) containing cationic liposomes/pDNA complexes in mice. Transfection efficiency after intravenous administration of complex at a charge ratio (- : +) of 1.0:2.3 and/or 1.0:3.1 in liver and spleen expressing a mannose receptor on the cell surface were higher than those in lung. When complexes were formed at a charge ratio (- : +) of 1.0:4.7, on the other hand, transfection efficiency in the lung was highest, suggesting a non-specific interaction. Although asialoglycoprotein receptors are expressed on hepatocytes, a liver-selective gene transfection was not achieved by the intravenous administration of pDNA complexed with cholesten-5-yloxy-N-[4-[(1-imino-2-D-thiogalactosyl-ethyl)-amino]butyl]formamide (Gal-C4-Chol)/DOPE liposomes at a charge ratio (- : +) of 1.0 : 2.3. This information supports the design of pDNA/ligands-grafted cationic liposome complexes for cell-specific gene delivery after intravenous administration.