Yang Zhihui, Zhu Jian, Sriadibhatla Srikanth, Gebhart Catherine, Alakhov Valery, Kabanov Alexander
Center for Drug Delivery and Nanomedicine and Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, 985830 Nebraska Medical Center, Omaha, NE 68198-5830, USA.
J Control Release. 2005 Nov 28;108(2-3):496-512. doi: 10.1016/j.jconrel.2005.08.015. Epub 2005 Sep 9.
Amphiphilic triblock copolymers of ethylene oxide and propylene oxide (Pluronic) significantly enhanced expression of plasmid DNA in the skeletal muscle. In the presence of Pluronic P85 (P85) high levels of expression of a reporter gene (luciferase) were sustained for at least 40 days and the area under the gene expression curve increased by at least 10 times compared to the DNA alone. The effect of Pluronic depended on the strain of the mouse and the type of the promoter used. Thus, P85 enhanced luciferase expression by 17 to 19-fold in immunocompetent C57Bl/6 and Balb/c mice, while no enhancement was observed with athymic Balb/c nu/nu mice. Furthermore, P85 activated the expression of luciferase gene driven by CMV promoter, NFkappaB and p53 response elements. There was much less or no effect on the gene driven by SV40 promoter or AP1 and CRE response elements. Overall, the promoter selectivity suggested that Pluronic induced transcriptional activation of gene expression by activating the p53 and NFkappaB signaling pathways. In addition Pluronic increased the number of DNA copies and thus affected initial stages of gene transfer in a promoter selective manner.
环氧乙烷和环氧丙烷的两亲性三嵌段共聚物（普朗尼克）显著增强了骨骼肌中质粒DNA的表达。在普朗尼克P85（P85）存在的情况下，报告基因（荧光素酶）的高水平表达持续了至少40天，与单独的DNA相比，基因表达曲线下的面积增加了至少10倍。普朗尼克的作用取决于小鼠的品系和所使用的启动子类型。因此，P85在免疫健全的C57Bl/6和Balb/c小鼠中使荧光素酶表达增强了17至19倍，而在无胸腺的Balb/c nu/nu小鼠中未观察到增强作用。此外，P85激活了由巨细胞病毒启动子、核因子κB和p53反应元件驱动的荧光素酶基因的表达。对由SV40启动子或AP1和CRE反应元件驱动的基因影响很小或没有影响。总体而言，启动子选择性表明普朗尼克通过激活p53和核因子κB信号通路诱导基因表达的转录激活。此外，普朗尼克增加了DNA拷贝数，从而以启动子选择性的方式影响基因转移的初始阶段。
