| Project/Area Number |
10470134
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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 |
Gastroenterology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
TABATA Yasuhiko Institute for Frontier Medical Sciences, Kyoto University, Professor, 再生医科学研究科, 教授 (50211371)
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| Co-Investigator(Kenkyū-buntansha) |
OKAZAKI Kazuichi Graduate School of Medicine, Kyoto University, Associate Professor, 医学研究科, 助教授 (70145126)
筏 義人 京都大学, 再生医科学研究所, 教授 (00025909)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥11,700,000 (Direct Cost: ¥11,700,000)
Fiscal Year 1999: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1998: ¥6,800,000 (Direct Cost: ¥6,800,000)
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| Keywords | Fullerene / Poly(ethylene glycol) / Water-soluble conjugate / Light irradiation / Anti-tumor activity / Photodynamic therapy |
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| Research Abstract |
Fullerene is known to efficiently generate singlet oxygen when irradiated with light. This will facilitate to induce a photodynamic effect on tumor, if its preferential accumulation in the tumor tissue is attained. To explore this tumor targeting of Fullerene, we chemically modified the water-insoluble fullerene with polyethylene glycol (PEG) not only to make fullerene soluble in water but also to enlarge its molecular size. When injected intravenously to mice carrying a tumor mass in the back subcutis, the large-sized, water-soluble fullerene-PEG conjugate exhibited higher accumulation and more prolonged fullerene retention in the tumor tissue than in the normal tissue. The conjugate was excreted from the body with time without being accumulated in a specific organ. Following intravenous injection of fullerene-PEG conjugates to the tumor-bearing mice coupled with exposure of the tumor site to visible light, the volume increase of the tumor mass was suppressed. Histological examination revealed that conjugate injection plus light irradiation strongly induced tumor necrosis without any damage to the overlaying normal skin. The antitumor effect of the conjugates increased with the increasing irradiation power and the fullerene dose, and the treatment with fullerene in a conjugate (424 g/kg) cured tumor at an irradiation power of 107 J/cmィイD12ィエD1. These findings indicate that the PEG-modified fullerene is a high potential agent for photodynamic tumor therapy.
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