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Research Articles: Therapeutics, Targets, and Development

Hepatocellular carcinoma cell-specific peptide ligand for targeted drug delivery

¹ Institute of Cellular and Organismic Biology, Academia Sinica; ² Institute of Pathology, College of Medicine, National Taiwan University; and ³ Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan

Requests for reprints: Han-Chung Wu, Institute of Cellular and Organismic Biology, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan. Phone: 886-2-2789-9558; Fax: 886-2-2785-8059. E-mail: hcw0928{at}gate.sinica.edu.tw

Abstract

Hepatocellular carcinoma is the fourth leading cause of cancer death worldwide. Novel treatment strategies derived from increased knowledge of molecular oncology are constantly being developed to cure this disease. Here, we used phage display to identify a novel peptide (SP94), which binds specifically to hepatocellular carcinoma cells. In vitro, the phage clone PC94 was shown to bind to hepatocellular carcinoma cell lines by ELISA and flow cytometry analysis. In vivo, PC94 homed specifically to tumor tissues but not to normal visceral organs in severe combined immunodeficient mice bearing human hepatocellular carcinoma xenografts. This homing ability could be competitively inhibited by synthetic peptide, SP94. Immunohistochemical staining confirmed that PC94 localized to tumor tissues and that it could not be detected in SP94-competed tumor tissues. In addition, PC94 recognized the tumor tissue but not nontumor tissue in surgical specimens from hepatocellular carcinoma patients, with a positive rate of 61.3% (19 of 31). With the conjugation of SP94 and liposomal doxorubicin, the targeted drug delivery system enhanced the therapeutic efficacy against hepatocellular carcinoma xenografts through enhanced tumor apoptosis and decreased tumor angiogenesis. Our results indicate that SP94 has the potential to improve the systemic treatment of patients with advanced hepatocellular carcinoma. [Mol Cancer Ther 2008;7(3):579–89]

Grant support: Academia Sinica and National Science Council Taiwan grant NSC-96-2323-B-001-002 (H-C. Wu).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Note: A. Lo and C-T. Lin contributed equally to this work.

⁴ Supplementary material for this article is available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/).

Received 12/ 3/07; accepted 1/ 4/08.