| Project/Area Number |
15500335
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biological material science
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| Research Institution | Sojo University |
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Principal Investigator |
MATSUMOTO Yoko Sojo University, Faculty of Engineering, Professor, 工学部, 教授 (00133562)
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| Co-Investigator(Kenkyū-buntansha) |
UEOKA Ryuichi Sojo University, Faculty of Engineering, Professor, 工学部, 教授 (70099076)
MATSUSHITA Taku Sojo University, Faculty of Engineering, Assistant Professor, 工学部, 助教授 (10209538)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | liposome / apoptosis / antitumor effect / caspase / chemotherapy / carcinoma mice / 肺がん |
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| Research Abstract |
Hybrid liposomes can be prepared by simply ultrasonicating a mixture of vesicular and micellar molecules in a buffer solution. The physical properties of these liposomes, such as size, membrane fluidity, phase transition temperature, and hydrophobicity can be controlled by changing the composition.
The inhibitory effects of hybrid liposomes composed of phospholipids having the same hydrophilic head group (phosphatidylcholine group) and different hydrophobic alkyl chains (L-α-dilauroylphosphatidylcholine (C_<12>: DLPC), L-α-dimyristoylphosphatidylcholine (C_<14>: DMPC), L-α-dipal-mitoylphosphatidylcholine (C_<16>:DPPC)) and polyoxyethylene-dodecyl ether (C_<12>(EO)_<23>) on the growth of human leukemia (HL60) cells in vitro were examined. Hybrid liposomes composed of DMPC and polyoxyethylene (10) dodecyl ether (C_<12>(EO)_<10>) were found to inhibit the growth of human promyelocytic leukemia (HL-60) cells without using any drugs.
Induction of apoptosis by hybrid liposomes in HL-60 cells was verified on the basis of fluorescence microscopy and flow cytometry analysis, after fusion and accumulation of hybrid liposomes which was revealed on the basis of microphysiometer. We elucidated the pathways of apoptosis induced by the hybrid liposomes. That is, hybrid liposomes fused and accumulated in tumor cell membranes, and the apoptosis signal first passed through mitochondria, caspase-9 and caspase-3, second through Fas, caspase-8, caspase-3 and then reached the nucleus. Hybrid liposomes themselves can induce apoptosis in human tumor cells along with high inhibitory effects on the growth of tumor cells.
We examined therapeutic effects of DMPC/C_<12>(EO)_<23> hybrid liposomes on mice model of carcinoma in vitro. The prolonged survival ratio of 150% was obtained in the treated with hybrid liposomes of DMPC/C_<12>(EO)_<23> without any side effects.
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