PEGylated DNA/transferrin-PEI complexes:: reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery
PEGylated DNA/transferrin-PEI complexes:: reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery
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DOI：
10.1038/sj.gt.3300900
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发表时间：
1999-04-01
期刊：
影响因子：
5.1
通讯作者：
Wagner, E
中科院分区：
文献类型：
--
作者：
Ogris, M;Brunner, S;Wagner, E
研究了DNA/转铁蛋白-聚乙烯亚胺（800 kDa）配合物在聚乙二醇（PEG）共价偶联前后的体内外性质。与血浆孵育后，带正电的非聚乙二醇化DNA复合物形成聚集体。血浆蛋白如IgM、纤维蛋白原、纤维连接蛋白和补体C3被发现与非聚乙二醇化的DNA复合物结合。在与体内基因传递相关的DNA浓度下，还观察到红细胞的强烈聚集，复合物的聚乙二醇化强烈减少血浆蛋白结合和红细胞聚集。此外，聚乙二醇化的配合物尺寸稳定，表面电荷减少。当静脉注射聚乙二醇化复合物时，也观察到血液循环延长。在荷瘤小鼠中，通过尾静脉应用非聚乙二醇化复合物可在衰竭和肺中表达报告基因，但在一些小鼠中观察到严重的毒性。相比之下，聚乙二醇化复合物介导的报告基因转移到肿瘤中没有明显的毒性。
We investigated the in vitro and in vivo properties of DNA/transferrin-polyethylenimine (800 kDa) complexes before and after covalent coupling of poly(ethylene glycol) (PEG). Upon incubation with plasma, the positively charged non-PEGylated DNA complexes form aggregates. Plasma proteins such as IgM, fibrinogen, fibronectin and complement C3 were found to bind to non-PEGylated DNA complexes. At DNA concentrations relevant for in vivo gene delivery a strong aggregation of erythrocytes was also observed PEGylation of the complexes strongly reduces plasma protein binding and erythrocyte aggregation. Furthermore, PEGylated complex size was stabilized and had a reduced surface charge. Prolonged circulation in the blood of the PEGylated complexes was also observed when injected intravenously. In tumor bearing mice, application of non-PEGylated complexes through the tail vein resulted in reporter gene expression in fail and lung, but severe toxicity was observed in some mice. in contrast, PEGylated complexes mediated reporter gene transfer to the tumor without significant toxicity.