Novel receptor-mediated gene delivery system comprising plasmid/protamine/sugar-containing polyanion ternary complex
Novel receptor-mediated gene delivery system comprising plasmid/protamine/sugar-containing polyanion ternary complex
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DOI：
10.1016/j.biomaterials.2003.10.004
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发表时间：
2004-07-01
期刊：
影响因子：
14
通讯作者：
Koyama, Y
中科院分区：
文献类型：
--
作者：
Maruyama, K;Iwasaki, F;Koyama, Y
将具有羧基和乳糖侧链的聚乙二醇（PEG）衍生物（Lac-PEG-C）沉积在DNA/鱼精蛋白（PRT）复合物表面，得到自组装的三元复合物。配合物的粒径为180-200 nm，在高离子强度溶液中也表现出良好的尺寸稳定性。Lac-PEG-C涂层降低了它们的表面电位，有效地避免了白蛋白诱导的聚集。DNA/PRT/Lac-PEG-C复合物对红细胞无凝血作用，WST-1法测定其细胞毒性很低。在与HepG 2细胞孵育之前将Lac-PEG-C加入到质粒/PRT复合物中极大地增强了基因表达，并且通过以1：1.5：8重量制备的质粒/PRT/Lac-PEG-C复合物，观察到荧光素酶的表达比没有Lac-PEG-C的高56倍。去唾液酸胎球蛋白或氧化苯胂处理明显干扰基因表达。质粒/PRT/Lac-PEG-C三元复合物在肝细胞上的高基因表达归因于脱唾液酸糖蛋白受体介导的内吞作用。(C)2003爱思唯尔有限公司。保留所有权利。
Poly(ethylene glycol) (PEG) derivative having both carboxylic acid-, and lactose-side chains (Lac-PEG-C) deposited onto the surface of DNA/protamine (PRT) complex, and the self-assembled ternary complex was obtained. The diameter of the complexes was 180-200 nm, and they showed good size stability even in the high ionic strength solutions. Lac-PEG-C coating reduced their surface electric potential, and effectively avoided the albumin-induced aggregation. DNA/PRT/Lac-PEG-C complex did not coagulate the red blood cells, and their cytotoxicity evaluated by WST-1 was very low. Lac-PEG-C added to the plasmid/PRT complex prior to the incubation with HepG2 cells extremely enhanced the gene-expression, and by the plasmid/PRT/Lac-PEG-C complex prepared at 1:1.5:8 in weight, 56-fold higher expression of luciferase than that without Lac-PEG-C was observed. The treatment with asialofetuin or phenylarsine oxide evidently interfered with the gene-expression. The high gene expression by the plasmid/PRT/Lac-PEG-C ternary complex on the hepatocyte would be attributed to the asialoglycoprotein receptor-mediated endocytosis. (C) 2003 Elsevier Ltd. All rights reserved.