Efficient gene transfer into macrophages and dendritic cells by in vivo gene delivery with mannosylated lipoplex via the intraperitoneal route
Efficient gene transfer into macrophages and dendritic cells by in vivo gene delivery with mannosylated lipoplex via the intraperitoneal route
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DOI：
10.1124/jpet.106.105098
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发表时间：
2006-08-01
影响因子：
3.5
通讯作者：
Hashida, Mitsuru
中科院分区：
文献类型：
--
作者：
Hattori, Yoshiyuki;Kawakami, Shigeru;Hashida, Mitsuru
在这项研究中，我们开发了一种抗原呈递细胞（APC）选择性腹腔内（i. p.）具有甘露糖基化阳离子脂质体（Man-liposomes）/质粒DNA复合物（Man-lipoplex）的基因递送系统。使用培养的腹腔巨噬细胞的体外研究表明，Man-脂质体可以通过甘露糖受体介导的机制比阳离子脂质体更有效地转染编码内切酶的质粒DNA（pCMV-Luc）。体内基因转染研究表明，腹腔注射后，Man-lipoplex在肝、脾、腹腔渗出细胞和肠系膜淋巴结中的基因表达高于阳离子脂质体/质粒DNA复合物（lipoplex）或裸pCMV-Luc，并且这种基因表达持续至少24 h。腹膜内给药后的Man-lipoplex的转染活性显著高于我们先前开发的Man-lipoplex静脉内基因递送后的转染活性，表明通过腹膜内途径进行基因递送似乎是体内基因递送至APC的有效方法。此外，证明Man-lipoplex可以增强脾中F4/80（+）和CD 11 c（+）细胞中的基因表达。这些结果表明，通过腹膜内途径用Man-脂质体进行基因递送可能是APC选择性基因转染的有效方法。
In this study, we developed an antigen-presenting cell (APC)selective intraperitoneal (i.p.)gene delivery system with mannosylated cationic liposomes (Man-liposomes)/plasmid DNA complex (Man-lipoplex). An in vitro study using cultured peritoneal macrophages demonstrated that Man-liposomes could transfect luciferase-encoding plasmid DNA (pCMV-Luc) more efficiently than cationic liposomes via a mannose receptor-mediated mechanism. In vivo gene transfection studies revealed that Man-lipoplex showed a higher gene expression in the liver, spleen, peritoneal exuded cells, and mesenteric lymph nodes than cationic liposomes/plasmid DNA complex (lipoplex) or naked pCMV-Luc after i.p. administration, and this gene expression lasted for at least 24 h. The transfection activity of Man-lipoplex after i.p. administration was significantly higher than that after i.v. gene delivery with the Man-liposomes we developed previously, indicating that gene delivery via the i.p. route seems to be an efficient approach for in vivo gene delivery to APCs. Furthermore, it was demonstrated that Man-lipoplex could enhance gene expression in both F4/80(+) and CD11c(+) cells in the spleen. These results show that gene delivery with Man-liposomes via the i.p. route could be an effective approach for APC-selective gene transfection.