Abstract 5521: Interleukin-4 receptor-targeted liposomal doxorubicin for enhanced targeted drug delivery and antitumor effect in colorectal cancer

Abstract

Abstract Previously and our studies have observed that colorectal tumor has high interleukin-4 receptor α (IL-4Rα) expression, whereas adjacent normal tissue has low or no IL-4Rα expression. We use human atherosclerotic plaque-specific peptide-1 (AP1) that specifically target to IL-4Rα. This study investigated the in vitro binding and internalization of AP1, specific targeting to IL-4Rα, therapeutic efficacy and systemic toxicity in vivo of AP1-conjuagted liposomal doxorubicin. In vitro, The AP1 strongly bound to and was efficiently internalized into IL-4Rα-overexpressed CT26 cells than CT26 control cells, while little binding and internalizing of a control peptide was seen. Selective cytotoxicity experiment revealed AP1-conjugated liposomal doxorubicin preferentially killed the IL-4Rα-overexpressed CT26 cells compared to control CT26 cells. In addition, AP1-conjugated liposomal doxorubicin administered intravenously significantly inhibited tumor growth and decreased cardiotoxicity of doxorubicin in subcutaneously tumor-bearing mouse model. These results indicated that AP1-conjugated liposomal doxorubicin has a potent and selective anticancer potential against IL-4Rα-overexpressed colorectal cancers. Citation Format: Chih-Yung Yang, Chi-Hong Lin, Jeng-Kai Jiang. Interleukin-4 receptor-targeted liposomal doxorubicin for enhanced targeted drug delivery and antitumor effect in colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5521. doi:10.1158/1538-7445.AM2015-5521