在体外和体内均使用聚乙二醇化脂质体评估了胆碱激酶（ChK）-siRNA对乳腺癌的抗癌作用。使用透明质酸（HA）和鱼精蛋白（CHK-siRNA + HA +鱼精蛋白）：脂质体的重量比在0.05和0.0037之间的重量比的缩合剂，可以实现siRNA /脂质体复合物的最佳大小和Zeta电位。当使用2.5mol％和5mol％的PEG化脂质体时，用ChK-siRNA处理对ChK-mRNA表达的抑制和所得的细胞生长抑制最高。小鼠静脉注射后的药代动力学研究表明曲线下面积（AUC）和血液半衰期（t 1/2，α和t 1/2，β在5 mol％聚乙二醇化脂质体中，ChK-siRNA的）分别比裸siRNA的高19倍和2.2至10.5倍。体内研究表明，带有siRNA的PEG-脂质比带有MDA-MB-231的异种移植裸鼠模型中的游离siRNA表现出更好的肿瘤生长抑制和更长的生存时间，这大概是由于半衰期增加和被动靶向由聚乙二醇化脂质体介导的效应。数据清楚地表明，聚乙二醇化脂质体与适当的缩合剂一起可以用作乳腺癌ChK-siRNA治疗剂的有效递送系统。
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Enhanced anticancer effect of liposome encapsulated choline kinase-siRNA in mice
The anticancer effect of choline kinase (ChK)-siRNA for breast cancer was evaluated using PEGylated liposomes both in vitro and in vivo. The optimal size and zeta-potential of siRNA/liposome complex were achieved using condensing agents of hyaluronic acid (HA) and protamine with weight ratios of (ChK-siRNA+HA+protamine): liposome between 0.05 and 0.0037. Suppression of the expression of ChK-mRNA and the resulting cell growth inhibition by the treatment with ChK-siRNA was the highest when using 2.5 and 5 mol% PEGylated liposomes. A pharmacokinetic study after intravenous injection into mice showed that the area under the curve (AUC) and blood half-life (t1/2, α and t1/2, β) of ChK-siRNA in 5 mol% PEGylated liposomes were 19 times and 2.2 to 10.5 times higher than that of naked siRNA, respectively. In vivo study showed that PEG-lipo with siRNA exhibited much better tumor growth inhibition and increased survival time than the free siRNA in an MDA-MB-231-bearing xenograft nude mouse model, presumably due to the increased half-life and the passive targeting effect mediated by the PEGylated liposome. The data clearly show that the PEGylated liposome, together with appropriate condensing agents, could serve as an effective delivery system for the ChK-siRNA therapeutics for breast cancer.
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