2010 Fiscal Year Final Research Report
Development of Nanotherapy System for Intractable Disease with Hybrid Liposomes-Cancer therapy with hybrid liposomes-
| Project/Area Number |
20360377
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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 | Sojo University |
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Principal Investigator |
UEOKA Ryuichi Sojo University, 生物生命学部, 教授 (70099076)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMOTO Yoko 崇城大学, 生物生命学部, 教授 (00133562)
MATSUSHITA Taku 崇城大学, 生物生命学部, 教授 (10209538)
GOTO Koichi 崇城大学, 生物生命学部, 教授 (30279377)
ICHIHARA Hideaki 崇城大学, 生物生命学部, 助教 (70369114)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 癌 / シグナル伝達 / トランスレーショナルリサーチ / 脂質 / 細胞・組織 |
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| Research Abstract |
We have produced hybrid liposomes (HL) which can be prepared by sonication of vesicular and micellar molecules in a buffer solution. The physical properties of HL such as size, shape, membrane fluidity, and the temperature of phase separation can be controlled by changing the constituents and compositional ratio. We have investigated the anticancer effects of HL and following results are obtained.
(A) The uniform and stable structure of HL-n composed of dimyristoylphosphatidylcholine (DMPC) and polyoxyethylene dodecyl ethers (C_<12>(EO)_n : n=21～25) with a diameter of 80 nm was observed by electron microscope and dynamic light scattering method.
(B) The remarkable inhibitory effects of HL on the growth of various tumor cells were attained in vitro.
(C) Reduction of mitochondrial membrane potential and activation of caspase-8, caspase-9, and caspase-3 were observed in the tumor cells treated with HL, indicating that apoptotic signal by HL-n should pass through mitochondria and these caspases.
(D) A good correlation between the membrane fluidity of HL and inhibitory effects of HL for tumor cells was obtained.
(E) Significantly high chemotherapeutic effects were obtained in vivo experiments using mice model of carcinoma after the treatment with HL without any drug.
(F) After the approval of the bioethics committee, prolonged survival was attained in patients with lymphoma after the intravenous injection of HL without any side effect.
The membrane targeted chemotherapy with drug-free HL was established for the first time.
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