Project/Area Number |
10450297
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
反応・分離工学
|
Research Institution | Ehime University |
Principal Investigator |
KATO Keiichi Ehime University, Assoc. Prof., 工学部, 助教授 (10117088)
|
Co-Investigator(Kenkyū-buntansha) |
SAEKI Toshiaki Inst Center of Shikoku Cancer-Therapy, Chief. Dr., 癌遺伝子研究室, 室長
TATEISHI Norihiko School of Medicine, Ehime Univ., Assist., 医学部, 助手 (90236555)
SATO Motomichi School of Medicine, Ehime Univ., Lect., 医学部, 講師 (50162491)
TAMASAKI Takashi Yamaki Co. Ltd, Research Dev., Chief Leader, 研究開発室, 室長
SUGAHARA Takuya College of Agriculture Ehume Univ., Assist., 農学部, 助手 (00263963)
|
Project Period (FY) |
1998 – 1999
|
Project Status |
Completed (Fiscal Year 1999)
|
Budget Amount *help |
¥11,100,000 (Direct Cost: ¥11,100,000)
Fiscal Year 1999: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1998: ¥6,400,000 (Direct Cost: ¥6,400,000)
|
Keywords | DDS / Cancer Therapy / Gene transfection / Lipid vesicle / Liposome / Immunovesicle / Alga lectin / Hybridoma |
Research Abstract |
The main purpose of this work is the new preparation of the lipid vesicle, which has a function of specific targeting to a cancer cell to apply to a cancer therapy. As a targeting ligand of "missile device" to a cancer cell, two species of ligands were chosen : one is Eucheuma serra (alga lectin) and another is a monochronal antibody to an antigen of a cancer cell. The ESA showed the specific affinity to a high-mannose. The ESA-immobilized vesicle was found to specifically combine to cancer cells, such asolon adenocarcinoma (COLO201). The vesicle flew smoothly in the supenor artery of rabbit. Moreover, the in-vivo experiments on the injection of the ESA-immobilized vesicle to a rat suggested a life safety of this vesicle because of the rat's living during 5 weeks without decrease in the weight. Another was an investigation on a cationic immnovesicle. The cationic vesicles were prepared by adding the cationic peptide lipids of N+C5Ala2C16 (abbreviated as CPL) to Span80 (sorbitan monooleate), by means of a two-step emulsification technique. Then, the anti-IgM antibody as a model ligand was immobilized to the vesicle (immunovesicle). The antigen of the antibody was the IgM. The IgM was produced at the surface of the human-human hybridoma (HB4C5 cell). The HB4C5 cell was chosen as a model-targeting cell, which was a fusion product of a human lymphocyte from lung cancer patient and a human lymphoma line, NAT-30. The specific binding and the fusion between the immnovesicles and the HB4C5 cells were confirmed by the fluorescence microscopic observation. The addition of the CPL to Span80 enhanced the fusion between the immunovesicles and HB4C5 cells. The transfection of the DNA entrapped in the immunovesicles to HB4C5 was also confirmed. Thus, the lipid vesicles were expected to be applied in a DDS or a gene transfection.
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