Developments of triple pH-activatable photosensitizer for highly selective photodynamic therapy of cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K05688
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 37010:Bio-related chemistry
• Research Institution: Gunma University
• Principal Investigator: HORIUCHI Hiroaki 群馬大学, 大学院理工学府, 准教授 (00334136)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 光増感剤 / がん / 光線力学療法 / pH応答性 / 一重項酸素 / 蛍光

Outline of Final Research Achievements

We have developed a photosensitizer with high cancer selectivity for use in near-infrared photodynamic therapy for cancer. This photosensitizer does not absorb near-infrared light under neutral conditions, which is a general biological environment. And even if it absorbs light, formation quantum yield of oxygen production and fluorescence quantum yield were quite low. This state is called tripe OFF state. On the other hand, when it accumulated in an acidic environment such as lysosome in cancer cells, this molecule turned to triple ON state, which means that it was able to efficiently absorb near-infrared light, generate singlet oxygen, and show fluorescence. We clarified the pH response mechanism. Based on this mechanism, we modified molecules for applications to biological systems, and obtained the molecular design strategies. Furthermore, it was clarified that it functions even in liposomes, which is a pseudo-biological environment.

Free Research Field

光化学

Academic Significance and Societal Importance of the Research Achievements

現在の主力のガン治療法は強力である反面、副作用も大きく、患者の生活の質の改善は重要である。光と薬剤を組み合わせた光線力学療法は非侵襲的なガン治療法として期待されている。しかしながら薬剤が正常組織中に分布することを完全に抑制することは困難であり、治療中の光や日常的な光による副作用が治療法の普及を妨げている要因の一つである。本課題では薬剤である光増感剤にトリプルpH応答性機能を付与したことにより、よりガン特異的な治療薬として期待でき、将来的に本課題のメカニズムを導入できれば、日帰り治療が可能な、手軽なガン治療法として普及できる可能性を有する。