Project/Area Number |
04044065
|
Research Category |
Grant-in-Aid for international Scientific Research
|
Allocation Type | Single-year Grants |
Section | Joint Research |
Research Institution | Tokyo Institute of Technology |
Principal Investigator |
OKURA Ichiro Tokyo Institute of Technology, 生命理工学部, 教授 (90089821)
|
Co-Investigator(Kenkyū-buntansha) |
NISHISAKA Tsuyosi Japan Advanced Institute of Science and Technology, 材料科学研究科, 教授 (40101084)
WOHRLE Dieter University of Bremen, 有機高分子学科, 教授
DIETER Wohrl ブレーメン大学, 有機高分子学科, 教授
|
Project Period (FY) |
1992 – 1994
|
Project Status |
Completed (Fiscal Year 1994)
|
Budget Amount *help |
¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1993: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
Keywords | Phthalocyanine / Porphyrin / Photodynamic Therapy / Photosensitizer / Hematoporphyrin / ヘマトポルフィリン誘導体 |
Research Abstract |
Photodynamic therapy (PDT) of cancer utilizing photosensitizers has been widely investigated. Though hematoporphyrin derivatives (HpD) have been used for PDT,they absorb little light of longer wavelengths (above 600 nm) which have good tissue penetration. In this study we synthesized zinc phthalocyanines with different degree of sulfonation, ZnTSPc and ZnSPc_<mix> and compared their tumor uptake, affinity to protein and phototoxicity. HeLa cells were incubated with both ZnTSPc and ZnSPc_<mix> solutions. Solutions were then removed and cells were washed with fresh medium followed by addition of 0.1 N NaOH.The maxima at 680 nm were observed especially in the case of ZnSPc_<mix>. This indicates that cellular uptake of ZnSPc_<mix> was better than that of ZnTSPc. It is concluded that ZnSPc_<mix> is more easily dissociated in cells than ZnTSPc. HeLa cells were irradiated by DCM dye laser after incubation with F-10 medium containing ZnTSPc or ZnSPc_<mix>. After irradiation, the trypan blue meth
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od was carried out. In the case of ZnTSPc, phototoxicity decreased with decreasing irradiation energy. In comparison, the phototoxicity by ZnSPc_<mix> was observed even at low dye concentration. Though the dye concentration and irradiation energy were low, HeLa Cells were damaged by irradiation with ZnSPc_<mix>. From the above results, ZnSPc_<mix> is a better sensitizer for PDT than ZnTSPc. Properties of zinc phthalocyanines sulfonated to difierent degrees were studied as sensitizers for PDT.From the spectrofluorometric analysis, ZnSPc_<mix> was incorporated in cells better than ZnTSPc. It was also clear that the affinity of ZnSPc_<mix> with serum proteins was higher than that of ZnTSPc. PDT experiment showed that cells were damaged by ZnSPc_<mix> even at low concentration and irradiation energy. Observation of the cell-dying process by SEM showed a large difference between cellular morphological changes by both compounds. This behavior of ZnSPc_<mix> depends on the increase of its penetration into cells due to the increase of its hydrophobicity. Less
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