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Anti-neovascular therapy using novel peptides homing to angiogenic vessels

Oncogene volume 21, pages 2662–2669 (2002)Cite this article

Abstract

Cancer chemotherapy targeted to angiogenic vessels is expected to cause indirect tumor regression through the damage of the neovasculature without the induction of drug resistance. To develop a tool for neovasculature-specific drug delivery, we isolated novel peptides homing to angiogenic vessels formed by a dorsal air sac method from a phage-displayed peptide library. Three distinct phage clones that markedly accumulated in murine tumor xenografts presented PRPGAPLAGSWPGTS-, DRWRPALPVVLFPLH- or ASSSYPLIHWRPWAR-peptide respectively. After the determination of the epitope sequences of these peptides, we modified liposomes with epitope penta-peptides. Liposome modified with APRPG-peptide showed high accumulation in murine tumor xenografts, and APRPG-modified liposome encapsulating adriamycin effectively suppressed experimental tumor growth. Finally, specific binding of APRPG-modified liposome to human umbilical endothelial cells, and that of PRP-containing peptide to angiogenic vessels in human tumors, i.e., islet cell tumor and glioblastoma, were demonstrated. The present study indicates the usefulness of APRPG-peptide as a tool for anti-neovascular therapy, a novel modality of cancer treatment.

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Acknowledgements

The authors thank Dr Yoji Ikawa at RIKEN for commenting on the manuscript. This work was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science and by Terumo Life Science Foundation. T Asai is a Research Fellow of the Japan Society for the Promotion of Science.

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Authors and Affiliations

  1. Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka, 422-8526, Japan

    Naoto Oku, Tomohiro Asai, Koh Watanabe, Koichi Kuromi, Mayumi Nagatsuka, Kohta Kurohane & Hironori Kikkawa

  2. Molecular Medical Science Institute, Otsuka Pharmaceutical Co., Ltd., 463-10 Kagasuno, Kawauchi-cho, Tokushima, 771-0192, Japan

    Koichi Ogino, Michinori Tanaka, Dai Ishikawa & Takao Taki

  3. Hamamatsu Photonics K.K., 5000 Hirakuchi, Hamakita, Shizuoka, 434-0041, Japan

    Hideo Tsukada

  4. Department of Laboratory Medicine and Central Clinical Laboratories, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan

    Masanobu Momose & Jun Nakayama

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  1. Naoto Oku
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  2. Tomohiro Asai
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  14. Takao Taki
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Correspondence to Naoto Oku.

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Oku, N., Asai, T., Watanabe, K. et al. Anti-neovascular therapy using novel peptides homing to angiogenic vessels. Oncogene 21, 2662–2669 (2002). https://doi.org/10.1038/sj.onc.1205347

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  • DOI: https://doi.org/10.1038/sj.onc.1205347

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