Targeting the prostate for destruction through a vascular address.
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.
Arap
Wadih
W
Cancer Research Center, The Burnham Institute, La Jolla, CA 92037, USA.
Haedicke
Wolfgang
W
Bernasconi
Michele
M
Kain
Renate
R
Rajotte
Daniel
D
Krajewski
Stanislaw
S
Ellerby
H Michael
HM
Bredesen
Dale E
DE
Pasqualini
Renata
R
Ruoslahti
Erkki
E
D000230:Adenocarcinoma / Q000098:blood supply / Q000473:pathology* / Q000821:virology; D000818:Animals; D017209:Apoptosis; D001435:Bacteriophages / Q000502:physiology*; D004730:Endothelium, Vascular / Q000821:virology*; D015723:Gene Library; D006801:Humans; D007425:Intracellular Membranes / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000473:pathology; D019151:Peptide Library; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000473:pathology* / Q000821:virology
D019151:Peptide Library