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

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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.

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Author and article information

Journal

Journal ID (nlm-ta): Cancer Biol Ther

Journal ID (iso-abbrev): Cancer Biol. Ther

Journal ID (pmc): KCBT

Title: Cancer Biology & Therapy

Publisher: Taylor & Francis

ISSN (Print): 1538-4047

ISSN (Electronic): 1555-8576

Publication date Collection: November 2015

Publication date (Electronic): 5 October 2015

Volume: 16

Issue: 11

Pages: 1641-1650

Affiliations

[1 ] Department of Education and Research; Taipei City Hospital ; Taipei, Taiwan

[2 ] Institute of Microbiology and Immunology, National Yang-Ming University ; Taipei, Taiwan

[3 ] Department of Surgery; National Yang-Ming University Hospital ; Yilan, Taiwan

[4 ] Drug Delivery Lab, Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute ; HsinChu, Taiwan

[5 ] Department of Surgery; Taipei City Hospital ; Taipei, Taiwan

[6 ] School of Medicine, National Yang-Ming University ; Taipei, Taiwan

[7 ] Division of Colon and Rectal Surgery; Department of Surgery; Taipei Veterans General Hospital ; Taipei, Taiwan

Author notes

^†These authors contributed equally to this work.

[* ]Correspondence to: Jeng-Kai Jiang; Email: jkjiang@ 123456vghtpe.gov.tw

Article

Accession ID: PMC4846110 Pmcid ID: PMC4846110 Pmc-uid ID: 4846110 Publisher ID: 1095397

DOI: 10.1080/15384047.2015.1095397

PMC ID: 4846110

PubMed ID: 26436767

SO-VID: 18780f7a-fe36-4821-8f7f-5b8d500accf0

History

Date received : 16 March 2015

Date revision received : 6 July 2015

Date accepted : 12 September 2015

Page count

Figures: 5, Tables: 0, References: 60, Pages: 10

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