Mishra Swaroop, Heidel Jeremy D, Webster Paul, Davis Mark E
Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
J Control Release. 2006 Nov 28;116(2):179-91. doi: 10.1016/j.jconrel.2006.06.018. Epub 2006 Jun 27.
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.
线性含环糊精聚阳离子（CDP）是众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，其转染效率会提高。据推测，缓冲活性赋予了增强的逃离内吞途径的能力。在此，研究了CDP与其含咪唑的pH缓冲变体（CDPim）之间递送行为的差异，以阐明这些相关材料在基因递送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比CDPim弱。然而，许多涉及转染细胞的分析表明，CDPim在细胞内环境中更容易释放核酸。这些数据共同表明，CDP和CDPim之间转染效率的差异是由缓冲活性和内体逃逸之外的因素导致的。
