Characterization of a pH-sensitive surfactant, dodecyl-2-(1'-imidazolyl) propionate (DIP), and preliminary studies in liposome mediated gene transfer.
Characterization of a pH-sensitive surfactant, dodecyl-2-(1'-imidazolyl) propionate (DIP), and preliminary studies in liposome mediated gene transfer.
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DOI：
10.1016/s0005-2736(97)00172-7
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发表时间：
1998-02
期刊：
影响因子：
--
通讯作者：
E. Liang;J. Hughes
中科院分区：
文献类型：
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作者：
E. Liang;J. Hughes
相对于病毒系统，非病毒基因递送系统的效率低下可能部分是由于内体在到达降解性溶酶体之前未能释放DNA。一种解决方案是将化合物掺入递送载体中，其将选择性地增加内体封装的DNA的释放。为了满足上述要求，我们设计、合成并表征了用于增强阳离子脂质体介导的基因传递的化合物2-（1′-咪唑基）丙酸十二烷基酯（DIP）的理化和生物学性质。几种表面活性技术被用来表征DIP裂解膜。DIP的临界胶束浓度在0.10-0.18 mM之间，有效释放和增溶比分别为1.0和4.0。DIP以pH和浓度依赖性方式促进膜破裂。在pH 7.0的酯酶存在下，水解速率增加32倍，表明DIP可以在生物环境中降解。在SKnSH细胞系中通过MTT测定的DIP的毒性证明了1.2mM的ID 50，其比用于增强基因转染的DIP浓度高30倍。当掺入阳离子脂质体中时，DIP使体外转基因表达增强5倍。研究结果表明，DIP可能是一种有用的佐剂，以增加非病毒基因递送到细胞。
The inefficiency of non-viral gene delivery systems, relative to viral systems, is likely due, in part, to the failure of endosomes to release DNA before reaching degradative lysosomes. A solution is to incorporate compounds in a delivery vector that will selectively increase the release of endosomally encapsulated DNA. To meet the above criteria, we designed, synthesized, and characterized the physicochemical and biological properties of such a compound, dodecyl-2-(1′-imidazolyl) propionate (DIP) to enhance cationic liposome mediated gene delivery. Several surface active techniques were used to characterize DIP lysing membranes. The critical micelle concentration of DIP was between 0.10–0.18 mM and the effective release and solubilization ratios were 1.0 and 4.0, respectively. DIP facilitated membrane disruption in both a pH and concentration dependent manner. In the presence of esterase at pH 7.0, the hydrolysis rate increased 32-fold indicating DIP can be degraded in the biological milieu. Toxicity of DIP by MTT assay in the SKnSH cell line demonstrated an ID50of 1.2 mM, which is 30-fold higher than the concentration of DIP used to enhance gene transfection. When incorporated into cationic-liposomes, DIP enhanced transgene expression in vitro by 5-fold. The results of the study indicate that DIP may be a useful adjuvant to increase non-viral gene delivery to cells.