The Design and Development of Molecular Probes for Evaluating the Malignancy of Cancer Stem Cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19027
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 33:Organic chemistry and related fields
• Research Institution: Kyoto University
• Principal Investigator: Ohe Kouichi 京都大学, 工学研究科, 教授 (90213636)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: がん幹細胞 / 酵素応答性プローブ / ESIDPT / 凝集誘起発光 / 活性酸素種

Outline of Final Research Achievements

To evaluate the malignancy of cancer stem cells, we have developed (1) dual-responsive molecular probes, (2) high-contrast visualization techniques for aldehyde dehydrogenase (ALDH) activity, and (3) probes aimed at responding to ALDH and other in vivo environmental stimuli while facilitating rapid probe excretion.
We synthesized a dual-responsive PiQ that responds to carboxylesterase (CE) and hydrogen peroxide, a reactive oxygen species in vivo, and established a technique for visualizing biological information.From the perspective of developing tools for evaluating the malignancy of cancer stem cells, we focused on improving the performance of the probe C5S-A, which responds to ALDH subtypes specifically expressed in cancer stem cells. We newly synthesized βC5S-A and evaluated the performance of the probe.

Free Research Field

有機合成化学・生物有機化学

Academic Significance and Societal Importance of the Research Achievements

がん幹細胞はがんの増殖や再発に大きく関与していることや通常のがん細胞と異なり薬物耐性が高いことが知られている．そのためその可視化技術の確立はがんの早期発見に加えて悪性度評価の観点から重要と考えられている．しかし，がん幹細胞を選択的に可視化できる分子プローブは本研究代表者らが開発したものを含め数例に限られている．また，悪性度の高いがん幹細胞を同定する技術開発も立ち遅れている．したがって，がん幹細胞の悪性度を識別できる高機能性分子プローブの開発は，効果的ながん治療につながるポテンシャルを秘めており，学術的価値とともに社会的意義が大きいと考えられる．