Interleukin-4 receptor-targeted liposomal doxorubicin as a model for enhancing cellular uptake and antitumor efficacy in murine colorectal cancer

摘要

Our previous studies showed that colorectal tumor has high interleukin-4 receptor (IL-4R) expression, whereas adjacent normal tissue has low or no IL-4R expression. We also observed that human atherosclerotic plaque-specific peptide-1 (AP1) can specifically target to IL-4R. In this study, we investigated the therapeutic efficacy and systemic toxicity of AP1-conjuagted liposomal doxorubicin. AP1 bound more strongly to and was more efficiently internalized into IL-4R-overexpressing CT26 cells than CT26 control cells. Selective cytotoxicity experiment revealed that AP1-conjugated liposomal doxorubicin preferentially killed IL-4R-overexpressing CT26 cells. AP1-conjugated liposomal doxorubicin administered intravenously into mice produced significant inhibition of tumor growth and showed decreased cardiotoxicity of doxorubicin. These results indicated that AP1-conjugated liposomal doxorubicin has a potent and selective anticancer potential against IL-4R-overexpressing colorectal cancer cells, thus providing a model for targeted anticancer therapy.