1. Interleukin-4 receptor-targeted liposomal doxorubicin as a model for enhancing cellular uptake and antitumor efficacy in murine colorectal cancer.
- Author
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Yang CY, Liu HW, Tsai YC, Tseng JY, Liang SC, Chen CY, Lian WN, Wei MC, Lu M, Lu RH, Lin CH, and Jiang JK
- Subjects
- Animals, Antibiotics, Antineoplastic metabolism, Antibiotics, Antineoplastic toxicity, Apoptosis drug effects, Cell Line, Tumor, Colorectal Neoplasms metabolism, Colorectal Neoplasms pathology, Doxorubicin metabolism, Doxorubicin toxicity, Drug Screening Assays, Antitumor, Humans, Liposomes, Male, Mice, Mice, Inbred BALB C, Neoplasm Transplantation, Peptides metabolism, Peptides toxicity, Treatment Outcome, Tumor Burden drug effects, Antibiotics, Antineoplastic administration & dosage, Colorectal Neoplasms drug therapy, Doxorubicin administration & dosage, Peptides administration & dosage, Receptors, Interleukin-4 metabolism
- Abstract
Our previous studies showed that colorectal tumor has high interleukin-4 receptor α (IL-4Rα) expression, whereas adjacent normal tissue has low or no IL-4Rα expression. We also observed that human atherosclerotic plaque-specific peptide-1 (AP1) can specifically target to IL-4Rα. 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-4Rα-overexpressing CT26 cells than CT26 control cells. Selective cytotoxicity experiment revealed that AP1-conjugated liposomal doxorubicin preferentially killed IL-4Rα-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-4Rα-overexpressing colorectal cancer cells, thus providing a model for targeted anticancer therapy.
- Published
- 2015
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