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

    Research output: Contribution to journalArticle

    231 Citations (Scopus)

    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., ... Ruoslahti, E. (2002). Targeting the prostate for destruction through a vascular address. PNAS, 99(3), 1527-1531. https://doi.org/10.1073/pnas.241655998

    Targeting the prostate for destruction through a vascular address. / Arap, W.; Haedicke, W.; Bernasconi, M.; Kain, Renate; Rajotte, D.; Krajewski, S.; Ellerby, H. M.; Bredesen, D. E.; Pasqualini, R.; Ruoslahti, E.

    In: PNAS, Vol. 99, No. 3, 2002, p. 1527-1531.

    Research output: Contribution to journalArticle

    Arap, W, Haedicke, W, Bernasconi, M, Kain, R, Rajotte, D, Krajewski, S, Ellerby, HM, Bredesen, DE, Pasqualini, R & Ruoslahti, E 2002, 'Targeting the prostate for destruction through a vascular address', PNAS, vol. 99, no. 3, pp. 1527-1531. https://doi.org/10.1073/pnas.241655998
    Arap W, Haedicke W, Bernasconi M, Kain R, Rajotte D, Krajewski S et al. Targeting the prostate for destruction through a vascular address. PNAS. 2002;99(3):1527-1531. https://doi.org/10.1073/pnas.241655998
    Arap, W. ; Haedicke, W. ; Bernasconi, M. ; Kain, Renate ; Rajotte, D. ; Krajewski, S. ; Ellerby, H. M. ; Bredesen, D. E. ; Pasqualini, R. ; Ruoslahti, E. / Targeting the prostate for destruction through a vascular address. In: PNAS. 2002 ; Vol. 99, No. 3. pp. 1527-1531.
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