Liver targeting of plasmid DNA with a cationized pullulan for tumor suppression
Liver targeting of plasmid DNA with a cationized pullulan for tumor suppression
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DOI：
10.1166/jnn.2006.466
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发表时间：
2006-09-01
影响因子：
--
通讯作者：
Tabata, Yasuhiko
中科院分区：
文献类型：
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作者：
Jo, Jun-iIchiro;Yamamoto, Masaya;Tabata, Yasuhiko
本研究的目的是利用普鲁兰多糖制备一种新型的基因载体，并评价其在小鼠肝脏基因转染中的可行性。通过化学引入精胺（精胺-普鲁兰）使重均分子量为22，800的普鲁兰阳离子化。将阳离子化的普鲁兰衍生物与质粒DNA复合并静脉内注射用于体内基因转染。精胺-普鲁兰多糖在肝脏中的基因表达水平取决于精胺引入的程度，并且观察到精胺-普鲁兰多糖的引入程度为5.60。当在接种RL male 1肿瘤细胞前1天将编码与精胺-普鲁兰多糖复合的肝细胞生长因子（HGF）/分散因子拮抗剂的NK 4的质粒DNA静脉注射到小鼠中时，荷瘤小鼠存活更长的时间，而GPT水平和在肝脏中生长的肿瘤细胞的数量与游离质粒DNA注射相比低。这些发现表明，通过与精胺-支链淀粉复合的NK 4质粒DNA的肝靶向特异性地增强了肝表达水平，导致对其中肿瘤生长的增强的抑制作用。
The objective of this study is to prepare a novel gene carrier from pullulan, a polysaccharide with an inherent affinity for the liver and evaluate the feasibility in gene transfection in the mice liver. Pullulan with a weight-average molecular weight of 22,800 was cationized by the chemical introduction of spermine (spermine-pullulan). The cationized pullulan derivative was complexed with a plasmid DNA and intravenously injected for in vivo gene transfection. The level of gene expression by the spermine-pullulan in the liver depended on the extent of spermine introduced and the highest level was observed for the spermine-pullulan with an introduction extent of 5.60. When a plasmid DNA coding NK4 of a hepatocyte growth factor (HGF)/scatter factor antagonist complexed with the spermine-pullulan was intravenously injected to mice 1 day before the inoculation of RLmale1 tumor cells, the tumor-bearing mice survived for a longer time period, while the GPT level and the number of tumor cells grown in the liver were low compared with those of free plasmid DNA injection. These findings indicate that the liver targeting of NK4 plasmid DNA by complexation with the spermine-pullulan specifically enhanced the liver expression level, resulting in augmented suppression effect on tumor growth therein.