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Joint Study on the Development of New PDT Photosensitizers

Research Project

Project/Area Number 04044065
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionTokyo 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)
KeywordsPhthalocyanine / 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 … More 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

Report

(3 results)
  • 1994 Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] T.Nishisaka,T.Fukami,and I.Okura: "Fluorescence compounds contained in tumor" J.Jap.Soc.Laser Med.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Nishisaka,T.Fukami,K.Tabata,D.Wohrle,and I.Okura: "Protoporphyrin and zinc protoporphyrin in the blood of tumor transplanted mice" Chem.Lett.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Kamachi,T.Hiraishi,and I.Okura: "Photoinduced hydrogen evolution with hydrogenase and Cytochrome c_3" Chem.Lett.33-34 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Kamachi,S.Uno,T.Hiraishi,and I.Okura: "Purification and properties of intact hydrogenase from Desulfovibrio vulgaris" J.Mol.Catal.,A:Chem.95. 93-98 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Takeno,J.Hirota,T.Kamachi,I.Okura,Y.Sakuma,and T.Nishisaka: "Characterization of sulfonated zinc phthalocyanines as photosensitizers for PDT" Lasers in the Life Sciences. 6. 173-178 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Nishisaka,O.Ishibashi,and I.Okura: "Reaction mechanism of photodynamic therapy with zinc phthalocyanine" Porphyrins. 3. 21-27 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 大倉一郎(分担): "生物物理化学" 講談社サイエンティフィク, 250 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 大倉一郎(分担): "光がかかわる触媒化学-光合成から環境化学まで-" 学会出版センター, 184 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Nishisaka, T.Fukami, and I.Okura: "Fluorescence compounds contained in tumor" J.Jap.Soc.Laser Med.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Nishisaka, T.Fukami, K.Tabata, D.Wohrle, and I.Okura: "Protoporphyrin and zinc protoporphyrin in the blood of tumor transplanted mice" Chem.Lett.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Kamachi, T.Hiraishi, and I.Okura: "Photoinduced hydrogen evolution with hydrogenase and Cytochrome c_3" Chem.Lett.33-34 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Kamachi, S.Uno, T.Hiraishi, and I.Okura: "Purification and properties of intact hydrogenase from Desulfovibrio vulgaris (Miyazaki)" J.Mol.Catal., A : Chem.95. 93-98 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Takeno, J.Hirota, T.Kamachi, I.Okura, Y.Sakuma, and T.Nishisaka: "Characterization of sulfonated zinc phthalocyanines as photosensitizers for PDT" Lasers in the Life Sciences. 6. 173-178 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Nishisaka, O.Ishibashi, and I.Okura: "Reaction mechanism of photodynamic therapy with zinc phthalocyanine" Porphyrins. 3. 21-27 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ichiro Okura et al.: Kodansha Scientific Publisher. Biophysical Chemistry, 250 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ichiro Okura et al.: Gakkai Shuppan Center. Chemisty of Photocatalysis-From Photosynthesis to Environmental Chemistry, 184 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] J.Hirota,T.Takeno,I.Okura: "Preparation and characterization of bisviologen-linked porphyrin" J.Photochem.Photobiol.A,Chem.77. 29-35 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] J.Hirota,I.Okura: "Photoinduced intramolecular electron transfer in bisviologen-linked prophyrin in acetonitrile" J.Phys.Chem.97. 6867-6870 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] S.Aono,T.Kamachi,I.Okura: "Membrane-bound hydrogenase from a Thermophilic hydrogen oxidizing bacterium,Bacillus schlegelii" Biosci,Biotech.Biochem.57. 1177-1179 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 大倉一郎: "金属ポルフィリンの光増感作用-太陽エネルギーの化学エネルギーへの変換を中心にして" ファルマシア. 29. 376-379 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 西坂剛、円入寛子、竹野哲、大倉一郎: "メチレンブルーを光増感剤とする光化学療法に関する研究" 日本化学会誌. 867-873 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 竹野哲,西坂剛,大倉一郎: "亜鉛スルホフタロシアニンを利用した光化学治療" 日本レーザー医学会誌. 14. 15-20 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 大倉一郎(分担): "実験化学講座" 丸善, 523 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 大倉一郎(分担): "化学ハンドブック" 朝倉書店, 1031 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 大倉一郎 他: "触媒技術の動向と展望" 触媒学会, 562 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ichiro OKURA: "Photoinduced intramolecular electron transfer in viologen linked zinc porphyrins in dimethyl sulfoxide" J.Phys.Chem.96. 4466-4469 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Shigetoshi AONO: "Photoinduced electron transfer between zinc protoporphyrin reconstituted myoglobin and methylviologen" Bull.Chem.Soc.Jpn.65. 591-593 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Shigetoshi AONO: "Purification and characterization of a 7-Fe ferredoxin from a Thermophilic hydrogen oxidizing bacterium,Bacillus schlegelii" J.Biochem.112. 792-795 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Ichiro OKURA: "Photoinduced intramolecular electron transfer in viologen-linked zinc porphyrins in acetonitrile" Inorg.Chim.Acta. 201. 11-13 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Tsuyoshi NISHISAKA: "Photodynamic therapy by porphyrin oligomer as tumor localizer" Lasers Life Sci.4. 87-92 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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