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Enhanced anticancer effect of liposome encapsulated choline kinase-siRNA in mice

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An Erratum to this article was published on 21 March 2014

Abstract

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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Authors and Affiliations

  1. Research Center for Cell Fate Control (RCCFC) & College of Pharmacy, Sookmyung Women’s University, Seoul, 140-742, Korea

    Dae Hwan Shin, Jae-Yeon Shim, Jung Hyun Kim, Seung Youn Lee, Shuhua Xuan, Woo-Young Kim & Jin-Seok Kim

  2. College of Pharmacy, Catholic University of Daegu, Gyeongbuk, 712-702, Korea

    Kwon Yeon Weon

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  1. Dae Hwan Shin
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  2. Jae-Yeon Shim
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  3. Jung Hyun Kim
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  4. Seung Youn Lee
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  5. Shuhua Xuan
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Correspondence to Jin-Seok Kim.

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Shin, D.H., Shim, JY., Kim, J.H. et al. Enhanced anticancer effect of liposome encapsulated choline kinase-siRNA in mice. Macromol. Res. 22, 344–355 (2014). https://doi.org/10.1007/s13233-014-2041-x

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  • DOI: https://doi.org/10.1007/s13233-014-2041-x

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