ScholarWorks@숙명여자대학교

초록

The anticancer effect of choline kinase (ChK)-siRNA for breast cancer was evaluated using PEGylatedliposomes both in vitro and in vivo. The optimal size and zeta-potential of siRNA/liposome complex were achievedusing 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 cellgrowth 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 10.5times higher than that of naked siRNA, respectively. In vivo study showed that PEG-lipo with siRNA exhibitedmuch better tumor growth inhibition and increased survival time than the free siRNA in an MDA-MB-231-bearingxenograft nude mouse model, presumably due to the increased half-life and the passive targeting effect mediated bythe PEGylated liposome. The data clearly show that the PEGylated liposome, together with appropriate condensingagents, could serve as an effective delivery system for the ChK-siRNA therapeutics for breast cancer.