Targeting the prostate for destruction through a vascular address

W. Arap, W. Haedicke, M. Bernasconi, Renate Kain, D. Rajotte, S. Krajewski, H. M. Ellerby, D. E. Bredesen, R. Pasqualini, E. Ruoslahti

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    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.

    Original languageEnglish
    Pages (from-to)1527-1531
    Number of pages4
    JournalPNAS
    Volume99
    Issue number3
    DOIs
    Publication statusPublished - 2002

    Keywords

    • VIVO PHAGE DISPLAY
    • CANCER
    • LIBRARIES
    • DELIVERY
    • PEPTIDES
    • MOUSE

    Cite this

    Arap, W., Haedicke, W., Bernasconi, M., Kain, R., Rajotte, D., Krajewski, S., Ellerby, H. M., Bredesen, D. E., Pasqualini, R., & Ruoslahti, E. (2002). Targeting the prostate for destruction through a vascular address. PNAS, 99(3), 1527-1531. https://doi.org/10.1073/pnas.241655998