Gene delivery using polyion complex micelle for the treatment of aortic aneurysm

使用聚离子复合胶束进行基因递送治疗主动脉瘤

基本信息

批准号：
17390345
负责人：
MIYATA Tetsuro
金额：
$ 9.38万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390345/
关键词：
Nano-material Surgery Circulation, Hypertension

项目摘要

(1) Development of novel polyion complex micelles (PCI micelles)To improve gene transfer efficiency, we developed two types of novel PCI micelles. One is PCI micelle added with circular RGD peptide. Circular RGD peptide could enhance delivery specificity of PCI micelle for endothelial cell and vascular smooth muscle cell. Another micelle is PEG-DET, which could promote intracellular-movement of micelle from endosome to cytoplasm (endosomal escape).(2) Mouse model of aortic aneurysmSince large amount of PCI micelle is necessary for gene delivery to rat aortic aneurysm, we aimed to establish mouse model of aortic aneurysm. Previous studies showed that continuous administration of angiotensin II potentially induced formation of aortic aneurysm. We tried the same protocol of angiotensin II administration to mouse, but aortic rupture due to dissection occurred in most of cases. Although we changed administration dose and delivery period, no formation of true aneurism was observed in mouse model.(3) Evaluation of gene transfer efficiency using neointimal model of rat carotid arteryBecause mouse model of aortic aneurysm could not be established, we decided to evaluate in vivo gene transfer efficiency of PCI micelle by delivering to neointima of rat carotid artery. First, rat carotid artery was injured with balloon catheter to induce neointimal lesion. At 3 weeks after the injury, PIC micelle containing marker gene DNA was administrated into the arterial lumen and incubated for 20 minutes. After the incubation, blood flow was resumed, and 3days later, gene expression was evaluated. Now, we are evaluating gene transfer efficiency of circular RGD-added PCI micelle on this model.

（1）开发新型的Polyion复合胶束（PCI胶束）以提高基因转移效率，我们开发了两种类型的新型PCI胶束。一种是添加了含有圆形RGD肽的PCI胶束。圆形RGD肽可以提高内皮细胞和血管平滑肌细胞的PCI胶束的递送特异性。另一个胶束是PEG-DET，它可以促进胶束从内体到细胞质的细胞内移动（内体逃逸）。（2）主动脉瘤的小鼠模型大量PCI胶束是基因递送到大鼠主动脉瘤的基因递送所必需的，我们旨在建立小鼠模型的主动脉瘤模型。先前的研究表明，连续施用血管紧张素II可能诱导的主动脉瘤的形成。我们尝试了对小鼠的血管紧张素II给药的相同方案，但是在大多数情况下，由于解剖引起的主动脉破裂。 Although we changed administration dose and delivery period, no formation of true aneurism was observed in mouse model.(3) Evaluation of gene transfer efficiency using neointimal model of rat carotid arteryBecause mouse model of aortic aneurysm could not be established, we decided to evaluate in vivo gene transfer efficiency of PCI micelle by delivering to neointima of rat carotid artery.首先，大鼠颈动脉用球囊导管受伤，以诱导新内膜病变。受伤后3周，将含有标记基因DNA的PIC胶束施加到动脉腔中并孵育20分钟。孵育后，恢复血液，然后在3天后评估基因表达。现在，我们正在评估该模型上圆形RGD增添PCI胶束的基因转移效率。