Cancer cell-specific imaging with the fluorescent probe responding by thymidine phosphorylase

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K05360
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 37030:Chemical biology-related
• Research Institution: Shibaura Institute of Technology
• Principal Investigator: Hatano Akihiko 芝浦工業大学, 工学部, 教授 (10333163)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: チミジンホスホリラーゼ / 過リン酸分解反応 / 蛍光プローブ / 癌診断 / 癌マーカー / 有機合成

Outline of Final Research Achievements

AAngiogenesis is the first step in the growth of cancer cells, and if this stage can be detected, it will lead to early detection. Thymidine phosphorylase (TP) is an angiogenic factor and is involved in the growth and metastasis of cancer cells. We considered that TP observation would be a marker for early detection of cancer cells. In this study, we developed a fluorescent probe that responds to the enzymatic activity of TP, which is an angiogenesis factor, and aimed to visualize the early development process of cancer cells. First, as a diagnostic agent whose fluorescence intensity changes with TP, we attempted to covalently bond a dansyl group as a fluorescent dye and a dabsyl group as a quenching agent to thymidine. When the TP response activity was evaluated using the synthesized probe, it was found that the phosphorolysis decomposition reaction proceeded by about 45% in 1 hour.

Free Research Field

酵素工学，生体関連化学

Academic Significance and Societal Importance of the Research Achievements

日本人の死因一位は癌である（約30％）。消化器官の内視鏡観察時に癌の疑いのある組織は，ヨード染色による目視判定が行われ，次に対象組織が採取されて病理検査が行われる。ヨード染色は簡便であるが副作用が問題である。癌の判定は組織を少量採取し，病理検査の結果を経て診断と癌組織の切除範囲が決定されるため，時間と労力がかかる。術中の薬剤塗布検査が病理検査と同じ精度で癌組織を検出できれば，癌組織の切除はリアルタイムで実施可能となり，正確，迅速，患者への負担軽減と再発防止に繋がると考えられる。そのため，簡単に癌細胞の場所を診断できるような新しいプローブ分子の開発が望まれている。