Pasqualini R, Ruoslahti E
La Jolla Cancer Research Center, The Burnham Institute, California 92037, USA.
Nature. 1996 Mar 28;380(6572):364-6. doi: 10.1038/380364a0.
Preferential homing of tumour cells and leukocytes 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, and an endothelial marker responsible for tumour homing to the lungs has also been identified. 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 was 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.
肿瘤细胞和白细胞向特定器官的优先归巢表明，组织携带有循环细胞可接触到的独特标记分子。已鉴定出内皮表面上的器官选择性地址分子，其可介导淋巴细胞归巢至各种淋巴器官以及发生炎症的组织，并且还鉴定出一种负责肿瘤归巢至肺部的内皮标记物。在此，我们报告一种基于对随机肽序列进行体内筛选来研究器官选择性靶向的新方法。鉴定出了能够介导噬菌体选择性定位于脑和肾血管的肽，并且这些肽对这些器官显示出高达13倍的选择性。合成了脑定位噬菌体展示的其中一种肽，并证明其可特异性抑制同源噬菌体定位于脑中。当包被在戊二醛固定的红细胞上时，该肽可使静脉注射的细胞选择性定位于脑中。这些肽序列代表了鉴定选择性内皮标记物的第一步，这可能有助于将细胞、药物和基因靶向至选定组织。
