A tissue factor targeted nanomedical system for thrombi-specific drug delivery
A tissue factor targeted nanomedical system for thrombi-specific drug delivery
复制标题
用于血栓特异性药物输送的组织因子靶向纳米医学系统。
DOI：
10.1016/j.biomaterials.2012.06.094
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发表时间：
2012-10-01
期刊：
影响因子：
14
通讯作者：
Hu, Yu
中科院分区：
文献类型：
--
作者：
Shi, Wei;Mei, Heng;Hu, Yu
组织因子（TF）是一种分子量为47 kDa的膜结合糖蛋白，在受损的内皮、动脉粥样硬化斑块或肿瘤血管中以高浓度存在，是凝血级联反应的重要触发因子。在本研究中，我们表达并纯化了TF靶向蛋白-EGFP-EGF 1，将其巯基化并与PEG-PLGA纳米颗粒的马来酰亚胺缀合，形成TF靶向纳米医学系统：EGF 1-EGFP-NP。该系统进行了仔细的特点和系统的靶向效率进行了评估。EGF 1-EGFP-NP可显著促进TF过表达的BCEC通过EGF 1/TF介导的内吞途径特异性摄取TF。此外，药代动力学研究表明，EGF 1-EGFP-NP具有与NP相同的血液循环时间。实时荧光图像显示，脑梗死区EGF 1-EGFP-NP表达增强。共聚焦显微镜和透射电镜进一步显示，EGF 1-EGFP-NP与TF结合，并通过受损的内皮进一步转染。体外细胞活性实验和体内凝血实验证实了EGF 1-EGFP-NP的安全性。(C)2012爱思唯尔有限公司保留所有权利。
Tissue factor (TF) is a 47 kDa membrane-bound glycoprotein, which is present at high concentrations on damaged endothelium, atherosclerotic plaques or tumor vasculature, and is an important trigger of coagulation cascade. In this study, we have expressed and purified the TF targeting protein-EGFP-EGF1, which was thiolated and conjugated to the malemide of the PEG-PLGA nanoparticle to form a TF targeting nanomedical system: EGF1-EGFP-NP. The system was carefully characterized and the targeting efficiency was systematically evaluated. The EGF1-EGFP-NP could significantly facilitate specific uptake by TF overexpressed BCEC via EGF1/TF mediated endocytosis pathway. In addition, the pharmacokinetic study demonstrated that EGF1-EGFP-NP has the same blood circulation time as NP. Enhanced accumulation of EGF1-EGFP-NP in the cortex infarction region was also observed by real-time fluorescence image. Confocal microscopy and TEM further showed that EGF1-EGFP-NP combined with TF and further transfected through the damaged endothelium. Moreover, in vitro cell viability experiment and in vivo coagulation ability confirmed that the EGF1-EGFP-NP was safe. (C) 2012 Elsevier Ltd. All rights reserved.