title: Interleukin-4 receptor-targeted liposomal doxorubicin as a model for enhancing cellular uptake and antitumor efficacy in murine colorectal cancer.
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.
authors.affiliation: a Department of Education and Research ; Taipei City Hospital ; Taipei , Taiwan.
authors.forename: Chih-Yung
authors.initials: CY
authors.lastname: Yang
authors.affiliation: b Institute of Microbiology and Immunology, National Yang-Ming University ; Taipei , Taiwan.
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Liu
authors.affiliation: b Institute of Microbiology and Immunology, National Yang-Ming University ; Taipei , Taiwan.
authors.forename: Ya-Ching
authors.initials: YC
authors.lastname: Tsai
authors.affiliation: b Institute of Microbiology and Immunology, National Yang-Ming University ; Taipei , Taiwan.
authors.forename: Ju-Yu
authors.initials: JY
authors.lastname: Tseng
authors.affiliation: b Institute of Microbiology and Immunology, National Yang-Ming University ; Taipei , Taiwan.
authors.forename: Shu-Ching
authors.initials: SC
authors.lastname: Liang
authors.affiliation: c Department of Surgery ; National Yang-Ming University Hospital ; Yilan , Taiwan.
authors.forename: Chin-Yau
authors.initials: CY
authors.lastname: Chen
authors.affiliation: b Institute of Microbiology and Immunology, National Yang-Ming University ; Taipei , Taiwan.
authors.forename: Wei-Nan
authors.initials: WN
authors.lastname: Lian
authors.affiliation: d Drug Delivery Lab, Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute ; HsinChu , Taiwan.
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Wei
authors.affiliation: d Drug Delivery Lab, Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute ; HsinChu , Taiwan.
authors.forename: Maggie
authors.initials: M
authors.lastname: Lu
authors.affiliation: e Department of Surgery ; Taipei City Hospital ; Taipei , Taiwan.
authors.forename: Ruey-Hwa
authors.initials: RH
authors.lastname: Lu
authors.affiliation: a Department of Education and Research ; Taipei City Hospital ; Taipei , Taiwan.|b Institute of Microbiology and Immunology, National Yang-Ming University ; Taipei , Taiwan.|f School of Medicine, National Yang-Ming University ; Taipei , Taiwan.
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Lin
authors.affiliation: f School of Medicine, National Yang-Ming University ; Taipei , Taiwan.|g Division of Colon and Rectal Surgery; Department of Surgery; Taipei Veterans General Hospital ; Taipei , Taiwan.
authors.forename: Jeng-Kai
authors.initials: JK
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000378:metabolism / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage* / Q000378:metabolism / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D010455:Peptides / Q000008:administration & dosage* / Q000378:metabolism / Q000633:toxicity; D019948:Receptors, Interleukin-4 / Q000378:metabolism*; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
chemical_list: C513345:AP1 peptide; D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D010455:Peptides; D019948:Receptors, Interleukin-4; D004317:Doxorubicin
keywords: AP1; colorectal cancer; interleukin-4 receptor α; targeted drug delivery