Targeting the prostate for destruction through a vascular address

被引:219
作者
Arap, W
Haedicke, W
Bernasconi, M
Kain, R
Rajotte, D
Krajewski, S
Ellerby, HM
Bredesen, DE
Pasqualini, R
Ruoslahti, E
机构
[1] Burnham Inst, Canc Res Ctr, La Jolla, CA 92037 USA
[2] Univ Vienna, Dept Ultrastruct Pathol & Cell Biol, A-1090 Vienna, Austria
关键词
D O I
10.1073/pnas.241655998
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:1527 / 1531
页数:5
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