The delivery of thrombi-specific nanoparticles incorporating oligonucleotides into injured cerebrovascular endothelium
The delivery of thrombi-specific nanoparticles incorporating oligonucleotides into injured cerebrovascular endothelium
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将掺有寡核苷酸的血栓特异性纳米粒子递送至受损的脑血管内皮中
DOI：
10.1016/j.biomaterials.2013.02.013
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发表时间：
2013-05-01
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
在急性血管事件中，内皮衍生组织因子（TF）是凝血级联的触发因子。本研究采用EGFP-EGF1蛋白偶联PEG-PLGA纳米颗粒作为TF靶向载体，将NF-kappa B诱骗寡核苷酸（ODNs）掺入其中，并评价所得EGF1-EGFP-NP-ODNs作为治疗皮层梗死的载体。转染TF表达的大鼠脑毛细血管内皮细胞2 h后，EGF1-EGFP-NP-ODNs比NP-ODNs更有效地内化并定位于细胞质中。在给药后4 h和6 h，细胞核中存在odn，并明显抑制TF的表达。体内静脉给药后6 h，大部分EGF1-EGFP-NP积聚在栓塞血管中，分布在受损内皮细胞中，降低TF表达。在给药24小时后，皮质梗死的MR成像主要减少。(c) 2013 Elsevier Ltd.版权所有。
In acute vascular events, the endothelium derived tissue factor (TF) is the trigger of the coagulation cascade. In this study, EGFP-EGF1 protein-conjugated PEG-PLGA nanoparticle was employed as a TF targeting vehicle, the NF-kappa B decoy oligonucleotides (ODNs) was incorporated into it and the resulting EGF1-EGFP-NP-ODNs were evaluated as a vector for therapy of cortex infarction. At 2 h after transfection of TF expressed rat brain capillary endothelial cell, EGF1-EGFP-NP-ODNs was more efficiently internalized and located in the cytoplasm than NP-ODNs. At 4 h and 6 h after administration, ODNs were present in the nuclei and obviously inhibited the TF expression. At 6 h after i.v. administration in vivo, most EGF1-EGFP-NP were accumulated in the embolism vessels, distributed in the damaged endothelial cells and lowered the TF expression. At 24 h after i.v. administration, MR imaging of cortex infarcts were predominantly dwindled. (c) 2013 Elsevier Ltd. All rights reserved.