Massive and selective delivery of lipid-coated cationic lipoplexes of oligonucleotides targeted in vivo to hepatic endothelial cells
Massive and selective delivery of lipid-coated cationic lipoplexes of oligonucleotides targeted in vivo to hepatic endothelial cells
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DOI：
10.1023/a:1015318415705
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发表时间：
2002-05-01
影响因子：
3.7
通讯作者：
Kamps, JAAM
中科院分区：
文献类型：
--
作者：
Bartsch, M;Weeke-Klimp, AH;Kamps, JAAM
目的.以前，我们报道了大量摄取的脂质体表面修饰的带负电荷的乌头酰白蛋白（Aco-HSA）的肝窦内皮细胞（EC）在体内。在目前的工作中，我们应用这一原则，在体内交付的反义寡核苷酸（ODN），这些细胞。抗ICAM-1 ODN与阳离子脂质DOTAP复合，并通过过量的中性脂质（包括脂质锚定的聚（乙二醇））包被复合物。将Aco-HSA偶联至包被的阳离子脂质复合物（CCL）。以[H-3]-胆固醇油醚和（3）2 P标记的ODN为标记物，观察Aco-HSA修饰的CCLs在大鼠体内的血浆消失、器官分布和肝内分布。Aco-HSA偶联的CCLs 90%存在于血液中。我们的研究结果表明，采用表面修饰有带负电荷白蛋白的血浆稳定涂层阳离子脂复合物，反义ODN在体内有效靶向EC。40%的注射ODN在30 min内被递送到靶细胞。
Purpose. Previously we reported on massive uptake of liposomes surface-modified with negatively charged aconitylated albumin (Aco-HSA) by liver sinusoidal endothelial cells (EC) in vivo. In the present work we applied this principle for the in vivo delivery of antisense oligonucleotides (ODN) to these cells.Methods. Anti ICAM-1 ODN was complexed with the cationic lipid DOTAP and the complex was coated by an excess of neutral lipids including a lipid-anchored poly(ethylene glycol). Aco-HSA was coupled to the coated cationic lipoplexes (CCLs). Plasma disappearance, organ and intrahepatic distribution of Aco-HSA modified CCLs were determined in rats, using [H-3]-cholesteryl oleyl ether and (3)2P-labeled ODN as markers.Results. The Aco-HSA coupled CCLs were 90% of the particles was in the blood.Conclusions. Our results demonstrate efficient targeting of antisense ODN to EC in vivo, employing plasma-stable coated cationic lipoplexes, surface modified with negatively charged albumin. 40% of the injected ODN was delivered to the target cells within 30 min.