| Project/Area Number |
16360415
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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 |
Biofunction/Bioprocess
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| Research Institution | Ehime University |
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Principal Investigator |
KATO Keiichi Ehime University, Graduate School of Science and Engineering, Associate Professor, 理工学研究科, 助教授 (10117088)
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| Co-Investigator(Kenkyū-buntansha) |
SUGAHARA Takuya Ehime University, Faculty of Agriculture, Associate Professor, 農学部, 助教授 (00263963)
AKIYAMA Koichi Ehime University, Integrated Center for Sciences, Assistant Professor, 総合科学研究支援センター, 助手 (80231835)
MASUDA Seizo Ehime University, Integrated Center for Sciences, Senior Assistant Professor, 総合科学研究支援センター, 講師 (50363263)
SUZUKI Yoji Ehime University, Graduate School of Medicine, Senior Assistant Professor, 医学系研究科, 講師 (20226567)
立石 憲彦 愛媛大学, 医学部, 助教授 (90236555)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2004: ¥11,000,000 (Direct Cost: ¥11,000,000)
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| Keywords | DDS / Cancer therapy / Apoptosis / Span80 / Liposome / Immunovesicle / Alga lectin / Gene transfection / Span80 / アポトーシス |
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| Research Abstract |
The main purpose of this work is the practical clinical application of the novel vesicle for a cancer therapy in drug delivery system (DDS), preparing a non-ionic surfactant vesicle, composed of Span80 (sorbitan monooleate). As the immobilized ligand as a "tumor-targeting missile device" on the Span80 vesicle, two species of ligands were chosen: (1) novel alga lectin ESA (Eucheuma Serra agglutinin:) and (2) monochronal antibody against the antigen of a tumor cell.
We revealed that Span80 was a surfactant mixture of sorbitan ester isomers of mono-, di-tri-and tetra-esters and the vesicle membrane was constructed as constant composition of the isomers by a thermodynamic self-assembly. The main component was diester (about 60%). Span80 vesicle had higher fluidity and superior characteristics such as membrane fusion, heat-satiability, metabolism and low-cost, compared with usual liposome with natural phospholipids. The ESA-immobilized Span80-vesicle (ESA vesicle) was revealed to specifically combine to cancer cells, such as colon adenocarcinoma (Colo201, Colon26) in vivo. We could also reveal that the ESA vesicle, injected to a mouse with the colon adenocarcinomas, transferred through the blood wall and targeted at the tumor following by the apoptotic death (confirmed by TUNNEL analysis) of the tumor. The vesicle accumulated in the liver was perfectly metabolized within 48 hours. The Span80 vesicle containing anticancer drug of docetaxcel (TXT) could perfectly controlled the mouse tumor. The influence of the vesicle size and the side effect could not be observed. The apoptotic mechanism (through Caspae3 and 8) was also clarified by genome-analysis. We could also demonstrate the effective control of the growth of the model human brain-tumor (from ERM5-1 cell) by injecting the immunovesicle immobilized with anti-EGFR antibody. Moreover, using the immunovesicle as a vector, gene transfection to the ERM5-1 tumor in vivo was successfully performed.
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