2007 Fiscal Year Final Research Report Summary
Gene delivery using polyion complex micelle for the treatment of aortic aneurysm
| Project/Area Number |
17390345
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | The University of Tokyo |
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Principal Investigator |
MIYATA Tetsuro The University of Tokyo, Hospital, Associate Professor (70190791)
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| Co-Investigator(Kenkyū-buntansha) |
KOYAMA Hiroyuki The University of Tokyo, Hospital, Project Associate Professor (10241994)
SHIGEMATSU Kunihuri The University of Tokyo, Hospital, Assistant Professor (20215966)
OBA Makoto The University of Tokyo, Hospital, Project Assistant Professor (20396716)
KIMURA Hideo The University of Tokyo, Hospital, Assistant Professor (60327070)
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| Project Period (FY) |
2005 – 2007
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| Keywords | Nano-material / Surgery / Circulation, Hypertension |
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| Research Abstract |
(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 aneurysm
Since 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 artery
Because 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.
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