| Project/Area Number |
12555262
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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 | 展開研究 |
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| Research Field |
高分子合成
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| Research Institution | NIIHAMA NATIONAL COLLEGE OF TECHNOLOGY |
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Principal Investigator |
SUNAMOTO Junzo NIIHAMA NATIONAL COLLEGE OF TECHNOLOGY President, 校長 (80037811)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASE Nobuki Department of Applied Chemistry and Biotechnology, Assistant Professor, 生物応用化学科, 助教授 (00311100)
USHIO Kazutoshi Department of Applied Chemistry and Biotechnology, Professor, 生物応用化学科, 教授 (30203508)
MANABE Masahiro Department of Applied Chemistry and Biotechnology, Professor, 生物応用化学科, 教授 (70044089)
LAI Douglas T. 日本学術振興会, 外国人特別研究員
DOUGLAS T.,Lai Japan Society for the Promotion of Science, post doctoral fellow
DAGULAS T. Lai 日本学術振興会, 外国人特別研究員
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥11,100,000 (Direct Cost: ¥11,100,000)
Fiscal Year 2001: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2000: ¥8,300,000 (Direct Cost: ¥8,300,000)
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| Keywords | cancer specific / drug carrier / folic acid / hydrophobized polysaoccharide / folate-modified / DDS |
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| Research Abstract |
In the present study, we have synthesized folate-modified cholesterol-bearing pullulan (FCHP) to develop cancer-specific drug carrier for various anticancer reagents.
FCHP was synthesized by the reaction of folic acid γ-2-aminoethylamide and 4-nitorophenyl chloroformate-activated cholesterol-bearing pullulan. The substitution ratio was estimated as 10% per glucoside units. FCHP was easily dissolved in PBS (or watcr) and formed macromolecular micelle either solely or with CHP. FCHP and FCHP-CHP nanoparticle seemed to stably bind doxorubicin a representative anticancer reagent, below the ratio of 0.02 : 5 (DOX : FCHP or FCHP-CHP, W/W).
Then, several combinations of FCHP, unmodified cholesterol-bearing pullulan (CHP) and doxorubicin (DOX) mixture were tested for cancer selective cytotoxicity. After pre-screening of several nanoparticle mixtures by the cancer cells-normal cells mixed cultivation system (a human epidermoid cancer KB cells known as expressing a high level of folate receptor, and a normal human fetal lung fibroblast TIG-1-20 cells were co-cultured in the same dishes), the cytotoxic effects of the nanoparticle mixtures for KB and TIG-1-20 in single cell cultivation system were separately quantified by cell counting using trypan blue method. FCHP (50 mg/L) itself was proved to have no cytotoxic effects toward human cells. Representatvely, a combination of FCHP-CHP-DOX of 1 : 4 : 0.02 (weight ratio, added to the cultivation medium at the concentration of 0.2 mg/L DOX) gave sharp and selective damage against cancer KB cells, while the same nanoparticle mixture only weakly damaged the growth of normal fibroblast TIG-1-20 cells. In addition, FCHP-CHP-DOX (1 : 4 : 0.02) complex seemed to be able to lead KB cells to the cell apoptosis more effectively than the same amount of DOX itself.
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