Targeting the prostate for destruction through a vascular address
Targeting the prostate for destruction through a vascular address
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DOI：
10.1073/pnas.241655998
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发表时间：
2002-02-05
影响因子：
11.1
通讯作者：
Ruoslahti, E
中科院分区：
文献类型：
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作者：
Arap, W;Haedicke, W;Ruoslahti, E
在小鼠身上探索了器官特异性药物靶向，作为治疗前列腺疾病手术的可能替代方案。通过选择能够在静脉注射后归巢到前列腺的噬菌体，从噬菌体展示的肽库中鉴定出能够识别前列腺中血管系统的多肽。注射。以这种方式选择的噬菌体中，有一个定位到前列腺的数量是定位到其他器官的10-15倍。未选择的噬菌体没有表现出这种偏好。噬菌体也与人类前列腺中的血管系统结合。合成了前列腺归巢噬菌体展示的多肽SMSIARL(单字母编码)，并证明当与该噬菌体共同注射到小鼠体内时，SMSIARL(单字母编码)可抑制该噬菌体的归巢。用一种由SMSIARL归巢多肽组成的嵌合肽对小鼠进行全身治疗，这种嵌合肽与破坏线粒体膜的促凋亡多肽相连，会导致前列腺组织破坏，但不会破坏其他器官。该嵌合肽延缓了易患前列腺癌的转基因小鼠(TRAMP小鼠)的癌症发展。这些结果表明，开发一种替代手术切除前列腺的方法是可能的，而且这种治疗方法也可能降低未来的癌症风险。
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.