Development of degradable polycyclic hosts that releases drugs and emits fluorescence in response to multiple external stimuli

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K05448
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 33010:Structural organic chemistry and physical organic chemistry-related
• Research Institution: Fukuoka University
• Principal Investigator: Hayashida Osamu 福岡大学, 理学部, 教授 (20231532)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: ホストゲスト化学 / 分子認識 / ゲスト放出 / 薬物送達 / ジスルフィド

Outline of Final Research Achievements

In this study, we developed host molecules that can more accurately release guest molecules (drugs) to cancer cells by breaking down in response to multiple external stimuli such as reducing agents and pH changes. We synthesized degradable host 1, which has a pH-responsive functional group in its side chain and a reduction-responsive disulfide in its molecular skeleton. The guest-binding ability of 1 changed in response to changes in pH, and it was possible to release guest molecules more effectively with the two stimuli of pH change and addition of a reducing agent. Furthermore, we synthesized a degradable host 2 that emits fluorescence upon addition of glutathione (GSH) as a reducing agent. By adding GSH, the disulfide bond of 2 was cleaved, and the released pyrene thiolate self-associated, successfully emitting excimer fluorescence.

Free Research Field

ホストゲスト化学

Academic Significance and Societal Importance of the Research Achievements

本研究では、還元剤や pH 変化などの複数の外部刺激に応答して分解し、捕捉したゲストを放出できる分解型ホスト分子を開発した。さらに、還元剤としてグルタチオンの添加に伴って、ジスルフィド結合が開裂し、放出したピレンのチオラート体が自己会合してエキシマー蛍光を発する分解型ホスト分子も合成した。これら分解型ホスト分子の分子設計と合成は、ホストゲスト化学や超分子化学の学術分野の発展に貢献するものであり、がん細胞を標的とした薬物送達システムの開発への基礎的知見を与えるものと期待される。