Application of Phage Display to Discovery of Tumor-Specific Homing Peptides: Developing Strategies for Therapy and Molecular Imaging of Cancer

  • Lee Seung-Min
  • Yoon Gil-Suk
  • Yoo Eun-Sang
  • Kwon Tae-Gyun
  • Kim In-San
  • Lee Byung-Heon
Part of the Methods in Molecular Biology™ book series (MIMB, volume 512)


Selective delivery of drugs or imaging dyes to tumor is the central challenge for improving existing therapy and diagnosis of cancer. Phage display of random peptides has been used to identify homing peptides that are specific to tumor cells or tumor blood vessels. These homing peptides can be conjugated with imaging agents or therapeutic drugs and may be a promising tool for affinity-based targeted delivery of imaging agents and drugs. This chapter describes the procedures for phage display selection of peptides that selectively bind to bladder tumor cells and home to tumor tissues in vivo. It also describes the application of the tumor-specific peptide to the detection of bladder cancer cells in the patient urine.

Key words

Bladder cancer Homing peptide Phage display Molecular imaging Targeted delivery 



This work was supported by the Ministry of Science and Technology (F104AA010003-06A0101-00310), grant No. RTI04-01-01 from the Regional Technology Innovation Program of the Ministry of Knowledge Economy (MKE), and Brain Korea 21 Project in 2006.


  1. 1.
    Reuter, V. E. and Melamed, M. R. (1989) The lower urinary tract. New York, Raven Press, pp. 1355–92.Google Scholar
  2. 2.
    Michaud, D. S. (2007) Chronic inflammation and bladder cancer Urol Oncol 25, 260–8.Google Scholar
  3. 3.
    Raghavan, D., Shipley, W. U., Garnick, M. B., Russell, P. J., and Richie, J. P. (1990) Biology and management of bladder cancer N Engl J Med 322, 1129–38.CrossRefPubMedGoogle Scholar
  4. 4.
    Wiener, H. G., Mian, C., Haitel, A., Pycha, A., Schatzl, G., and Marberger, M. (1998) Can urine bound diagnostic tests replace cystos-copy in the management of bladder cancer? J Urol 159, 1876–80.CrossRefPubMedGoogle Scholar
  5. 5.
    Ruoslahti, E. (2002) Specialization of tumor vasculature Nat Rev Cancer 2, 83–90.CrossRefPubMedGoogle Scholar
  6. 6.
    Pasqualini, R. and Ruoslahti, E. (1996) Organ targeting in vivo using phage display peptide libraries Nature 380, 364–6.CrossRefPubMedGoogle Scholar
  7. 7.
    Lee, S. M., Lee, E. J., Hong, H. Y., Kwon, M. K., Kwon, T. H., Choi, J. Y., Park, R. W., Kwon, T. G., Yoo, E. S., Yoon, G. S., Kim, I. S., Ruoslahti, E., and Lee, B. H. (2007) Targeting bladder tumor cells in vivo and in the urine with a peptide identified by phage display Mol Cancer Res 5, 11–19.CrossRefPubMedGoogle Scholar
  8. 8.
    Smith, G. P. (1985) Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface Science 228, 1315–17.CrossRefPubMedGoogle Scholar
  9. 9.
    Pasqualini, R., Koivunen, E., and Ruoslahti, E. (1997) Alpha v integrins as receptors for tumor targeting by circulating ligands Nat Biotechnol 15, 542–6.CrossRefPubMedGoogle Scholar
  10. 10.
    Ladner, R. C., Sato, A. K., Gorzelany, J., and de Souza, M. (2004) Phage display-derived peptides as therapeutic alternatives to antibodies Drug Discov Today 9, 525–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Hoffman, J. A., Laakkonen, P., Porkka, K., Ber-nasconi, M., and Ruoslahti, E. (2004) In vivo and ex vivo selections using phage-displayed libraries In: T. Clackson, Lowman, H. B. (ed.), Phage display, 1st edition, Vol. 266. New York, Oxford University Press, pp. 171–92.Google Scholar
  12. 12.
    Ohyama, C., Kawamura, S., Satoh, M., Saito, S., Yoshikawa, K., Hoshi, S., and Orikasa, S. (1997) Endoscopic observation for detection and monitoring of N-butyl-N-(4-hydroxy-butyl)nitrosamine-induced bladder tumor in rats Urol Res 25, 183–6.CrossRefPubMedGoogle Scholar
  13. 13.
    Azzazy, H. M. and Highsmith, W. E., Jr. (2002) Phage display technology: clinical applications and recent innovations Clin Bio-chem 35, 425–45.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Lee Seung-Min
    • 1
  • Yoon Gil-Suk
  • Yoo Eun-Sang
  • Kwon Tae-Gyun
    • 2
  • Kim In-San
    • 1
  • Lee Byung-Heon
    • 1
  1. 1.Department of Biochemistry and Cell Biology and Cell & Matrix Research InstituteDaeguKorea
  2. 2.Department of Urology, School of MedicineKyungpook National UniversityDaeguKorea

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