Effect of the particle size of galactosylated lipoplex on hepatocyte-selective gene transfection after intraportal administration
Effect of the particle size of galactosylated lipoplex on hepatocyte-selective gene transfection after intraportal administration
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DOI：
10.1248/bpb.29.1521
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发表时间：
2006-07-01
影响因子：
2
通讯作者：
Hashida, Mitsuru
中科院分区：
文献类型：
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作者：
Higuchi, Yuriko;Kawakami, Shigeru;Hashida, Mitsuru
本研究旨在探讨半乳糖化阳离子脂质体（Gal-liposome）/质粒DNA复合物（Gal-lipoplex）大小对门静脉注射后肝细胞选择性基因转染的影响。选择pCMV-Luc作为模型质粒DNA。小鼠门静脉内注射Gal-lipoplex后，评价了肝脏和肝内基因表达。为了评估尺寸的影响，制备了三种不同尺寸的Gal-脂质体。Gal-lipoplex的平均粒径分别为约141、179和235 nm。通过增加Gal-lipoplex的大小，肝转染效率显著增强。而在141 μ m左右的肝实质细胞中，Gal-lipoplex的基因表达量明显高于非实质细胞。与此相反，约235 μ m的Gal-lipoplex在PC中的基因表达显著低于NPC。这些结果突出了Gal-lipoplex大小对于体内肝细胞选择性基因转移的重要性。本研究中的信息将是有价值的未来使用，设计和开发的半乳糖-lipoplex在体内应用。
The purpose of this study was to examine the effect of the size of galactosylated cationic liposome (Gal-liposome)lplasmid DNA complex (Gal-lipoplex) on hepatocyte-selective gene transfection after intraportal administration. pCMV-Luc was selected as a model plasmid DNA. After intraportal administration of Gal-lipoplex to mice, the hepatic and intrahepatic gene expression was evaluated. To evaluate the effect of size, three different sizes of Gal-liposome were prepared. The mean particle sizes of Gal-lipoplex were about 141, 179, and 235 mn, respectively. The hepatic transfection efficacy was significantly enhanced by increasing the size of Gal-lipoplex. However, the gene expression in liver parenchymal cells (PC) of Gal-lipoplex of about 141 urn in size was significantly higher than that in liver non-parenchymal cells (NPC). In contrast, gene expression in PC of Gal-lipoplex of about 235 urn in size was significantly lower than that in NPC. These results highlight the importance of the Gal-lipoplex size for hepatocyte-selective gene transfer in vivo. The information in this study will be valuable for the future use, design, and development of Gal-lipoplex for in vivo applications.