Organ targeting in vivo using phage display peptide libraries
Organ targeting in vivo using phage display peptide libraries
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DOI：
10.1038/380364a0
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发表时间：
1996-03-28
期刊：
影响因子：
64.8
通讯作者：
Ruoslahti, E
中科院分区：
文献类型：
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作者：
Pasqualini, R;Ruoslahti, E
肿瘤细胞（1,2）和白细胞（3,4）对特定器官的优先寄养表明，组织携带可循环细胞可访问的独特标记分子。在内皮表面上的器官选择性分子已被鉴定出对各种淋巴机构和受炎症的组织的淋巴细胞归巢（5-8）的组织（5-8），并且还鉴定出了负责肺部肿瘤归巢的内皮标记物（9）（9）。在这里，我们报告了一种基于随机肽序列的体内筛查来研究器官选择靶向的新方法。鉴定出能够介导噬菌体在脑和肾血管中选择性定位的肽，并对这些器官表现出多达13倍的选择性。脑部位置噬菌体MAS所显示的肽之一合成并显示为特异性抑制同源噬菌体在大脑中的定位。当涂在戊二醛固定的红细胞上时，肽会导致静脉注射细胞的选择性定位到大脑中，这些肽序列代表了识别选择性内皮标记的第一步，这可能在靶向细胞，药物和基因中有用。
PREFERENTIAL homing of tumour cells(1,2) and leukocytes(3,4) to specific organs indicates that tissues carry unique marker molecules accessible to circulating cells. Organ-selective address molecules on endothelial surfaces have been identified for lymphocyte homing to various lymphoid organs and to tissues undergoing inflammation(5-8), and an endothelial marker responsible for tumour homing to the lungs has also been identified(9). Here we report a new approach to studying organ-selective targeting based on in vivo screening of random peptide sequences. Peptides capable of mediating selective localization of phage to brain and kidney blood vessels were identified, and showed up to 13-fold selectivity for these organs. One of the peptides displayed by the brain-localizing phage mas synthesized and shown to specifically inhibit the localization of the homologous phage into the brain. When coated onto glutaraldehyde-fixed red blood cells, the peptide caused selective localization of intravenously injected cells into the brain, These peptide sequences represent the first step towards identifying selective endothelial markers, which may be useful in targeting cells, drugs and genes into selected tissues.