A synthetic peptide mediated active targeting of cisplatin liposomes to Tie2 expressing cells
A synthetic peptide mediated active targeting of cisplatin liposomes to Tie2 expressing cells
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DOI：
10.1016/j.jconrel.2009.06.024
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发表时间：
2009-11-03
影响因子：
10.8
通讯作者：
Xu, Yuhong
中科院分区：
文献类型：
--
作者：
Mai, Junhua;Song, Shuxian;Xu, Yuhong
Tie 2受体是一种酪氨酸激酶受体，在血管新生中起重要作用，在多种肿瘤细胞中高度表达。在这项研究中，我们报道了一种由新型肽配体PHI指导的主动靶向脂质体系统，该系统可以提高特异性针对Tie 2表达细胞的药物功效。通过噬菌体展示文库筛选结合表面等离子体共振结合测定来选择PH 1肽（TMGFTAPRFPHY）。它与DSPE-PEG（2000）-马来酰亚胺脂质的远端共价结合，并作为靶向配体加载到脂质体膜上。这些含有抗癌药物顺铂的PH 1-PEG-脂质体显示与Tie 2阳性细胞紧密结合，介导含有药物的脂质体的主动内吞作用，并且导致比mPEG涂覆的脂质体高得多的细胞特异性细胞毒性。它们不仅可用于靶向血管内皮细胞以实现抗血管生成作用，而且可用于改善表达Tie 2的癌细胞中的药物递送和释放。这种脂质体制剂可以发展成为一种非常有用的节拍化疗剂。(C)2009 Elsevier B. V.保留所有权利。
Tie2 receptor is a receptor tyrosine kinase that plays important roles in vascular angiogenesis, and also highly expressed by a number of cancer cells. In this study, we reported an active targeting liposome system directed by a novel peptide ligand PHI that can improve drug efficacies specifically to Tie2 expressing cells. The PH1 peptide (TMGFTAPRFPHY) was selected by phage display library screening combined with surface plasmon resonance binding assays. It was covalently conjugated to the distal end of DSPE-PEG(2000)-Maleimide lipid and loaded onto liposome membranes as the targeting ligand. These PH1-PEG-liposomes containing the anticancer drug cisplatin were showed to bind tightly to Tie2 positive cells, mediate active endocytosis of the drug containing liposomes, and result in much higher cell specific cytoxicities than mPEG coated liposomes. They can be used not only to target vascular endothelial cells for anti-angiogenesis effects, but also to improve drug delivery and release in Tie2 expressing cancer cells. Such liposome formulation may be developed into a very useful agent for metronomic chemotherapy. (C) 2009 Elsevier B.V. All rights reserved.