Imidazole groups on a linear, cyclodextrin-containing polycation produce enhanced gene delivery via multiple processes
Imidazole groups on a linear, cyclodextrin-containing polycation produce enhanced gene delivery via multiple processes
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DOI：
10.1016/j.jconrel.2006.06.018
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发表时间：
2006-11-28
影响因子：
10.8
通讯作者：
Davis, Mark E.
中科院分区：
文献类型：
--
作者：
Mishra, Swaroop;Heidel, Jeremy D.;Davis, Mark E.
线性的、含环糊精的聚阳离子（CDP）是许多非病毒基因递送载体之一，当被修饰为具有pH缓冲能力时，其显示出改善的转染效率。推测缓冲活性赋予增强的逃避内吞途径的能力。在这里，CDP和它的pH缓冲，含咪唑的变体（CDPim）之间的传递行为的差异进行了研究，以阐明这些相关材料在基因传递中表现出差异的机制。在包括染料排斥和硫酸乙酰肝素置换的无细胞测定中，CDP与核酸的结合强度似乎弱于CDPim。然而，涉及转染细胞的许多分析表明，CDPim更容易在细胞内环境中释放核酸。总之，这些数据表明CDP和CDPim之间转染效率的差异是由缓冲活性和内体逃逸以外的因素造成的。(c)2006 Elsevier B.V.保留所有权利。
The linear, cyclodextrin-containing polycation (CDP) is one of many non-viral gene delivery vectors that show improved transfection efficiency when modified to have pH-buffering capacity. The buffering activity is presumed to confer enhanced ability to escape the endocytic pathway. Here, the differences in delivery behavior between CDP and its pH-buffering, imidazole-containing variant (CDPim) are investigated in order to elucidate the mechanism(s) by which these related materials exhibit differences in gene delivery. In cell-free assays that include dye exclusion and heparan sulfate displacement, CDP appears to have weaker binding strength with nucleic acids than CDPim. Numerous analyses involving transfected cells, however, indicate that CDPim more readily releases nucleic acids in the intracellular setting. Together, these data suggest that differences in transfection efficiency between CDP and CDPim result from factors beyond buffering activity and endosomal escape. (c) 2006 Elsevier B.V. All rights reserved.