Targeting the prostate for destruction through a vascular address

Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1527-31. doi: 10.1073/pnas.241655998.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / blood supply
  • Adenocarcinoma / pathology*
  • Adenocarcinoma / virology
  • Animals
  • Apoptosis
  • Bacteriophages / physiology*
  • Endothelium, Vascular / virology*
  • Gene Library
  • Humans
  • Intracellular Membranes / pathology
  • Male
  • Mice
  • Mice, Transgenic
  • Mitochondria / pathology
  • Peptide Library
  • Prostatic Neoplasms / blood supply
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / virology

Substances

  • Peptide Library