| Project/Area Number |
17H03086
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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 |
Bio-related chemistry
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| Research Institution | Shizuoka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
村上 浩雄 浜松医科大学, 医学部附属病院, 助教 (10432212)
金山 尚裕 浜松医科大学, 医学部, 副学長 (70204550)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
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| Keywords | 光線力学的療法 / 光増感剤 / がん治療 / ポルフィリン / 電子移動 / 活性制御 / 一重項酸素 / タンパク質損傷 / 細胞毒性 / がん細胞選択性 / 抗腫瘍活性 / がん選択性 / 生体分子 / 光物性 / 癌 / 薬理学 / 有機化学 |
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| Outline of Final Research Achievements |
Photodynamic therapy is less-invasive treatment for cancer. A less-toxic administered photosensitizers induce oxidative damage to biomacromolecules under visible-light irradiation, resulting in necrosis or apoptosis of cancer cells. However, the traditional photosensitizers require oxygen and their effects are restricted under hypoxia. To solve this problem, novel P(V)porphyrin photosensitizers were designed and synthesized. These P(V)porphyrins could photosensitize the protein oxidation through electron transfer. Cancer-selective photocytotoxicity and a significant photodynamic effect on a mouse tumor model by these P(V)porphyrins were demonstrated. By the substitution of the axial ligand of P(V)porphyrins, the target-selective photooxidation through the self-aggregation was possible. In addition, using the pyridyl moiety as an electron donor, the photosensitizing activity of P(V)porphyrins could be controlled by pH to realize the selective treatment of the acidic cancer cells.
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| Academic Significance and Societal Importance of the Research Achievements |
電子移動でがん細胞に酸化ダメージを与えるP(V)ポルフィリン光増感剤を合成し、新しい概念の光治療を提唱した。合成したP(V)ポルフィリンは、がん細胞選択性に優れるが、分子修飾によりターゲット選択性の向上やがん細胞内のような弱酸性環境での活性制御にも成功した。
我が国は、超高齢社会となって久しく、止血が困難なために手術できない患者が増加している。低侵襲ながん治療が重要であり、その代表例といえる放射線治療等は、大掛かりな医療設備が必要で高額である。本研究の成果は、簡便で低コストな光線力学的療法の従来の課題を克服したことであり、新たな低侵襲がん治療法の実現と普及へつながる可能性をもつ。
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