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Targeting the prostate for destruction through a vascular address

  • Wadih Arap
  • Wolfgang Haedicke
  • Michele Bernasconi
  • Renate Kain
  • Daniel Rajotte
  • Stanislaw Krajewski
  • H. Michael Ellerby
  • Dale E. Bredesen
  • Renata Pasqualini
  • Erkki Ruoslahti
The National Academy of Sciences
Publication Date
Feb 05, 2002
  • Medicine


Organ specific drug targeting was explored in mice as a possible alternative to surgery to treat prostate diseases. Peptides that specifically recognize the vasculature in the prostate were identified from phage-displayed peptide libraries by selecting for phage capable of homing into the prostate after an i.v. injection. One of the phage selected in this manner homed to the prostate 10–15 times more than to other organs. Unselected phage did not show this preference. The phage bound also to vasculature in the human prostate. The peptide displayed by the prostate-homing phage, SMSIARL (single letter code), was synthesized and shown to inhibit the homing of the phage when co-injected into mice with the phage. Systemic treatment of mice with a chimeric peptide consisting of the SMSIARL homing peptide, linked to a proapoptotic peptide that disrupts mitochondrial membranes, caused tissue destruction in the prostate, but not in other organs. The chimeric peptide delayed the development of the cancers in prostate cancer-prone transgenic mice (TRAMP mice). These results suggest that it may be possible to develop an alternative to surgical prostate resection and that such a treatment may also reduce future cancer risk.

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