2023 Fiscal Year Annual Research Report
Precisely activating ferroptosis by Fe(II)-triggered drug release for enhanced cancer therapy
| Project/Area Number |
22K20530
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| Research Institution | Kyoto University |
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Principal Investigator |
MU Huiying 京都大学, 工学研究科, 助教 (80967399)
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| Project Period (FY) |
2022-08-31 – 2024-03-31
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| Keywords | Fe2+ / fluorescent dye / cleavage / pH-responsive / tumor imaging |
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| Outline of Annual Research Achievements |
In the year of FY2023, we prepared various molecules to evaluate the Fe2+-triggered reaction based on this project. The oxime ester was used as a promising cleavage linker for fluorescent dye with a tunable substituent. And we evaluated the effects of various substituents on the Fe2+-mediated reactions, including electron-donated/withdrawing moieties and FRET-paired fluorophores, and etc. The fluorescence output of probes was chosen to investigate their cleavage of oxime ester by Fe2+ in various conditions. It was hound that a good ratiometric properties of the FRET-type probe was achieved upon the activation of Fe2+. However, the stability of probe should be furtherly adjusted due to its high electron-withdrawing property of substituent. This research will be continued to conduct in the future.
In addition, we designed and developed a fluorescent sensor CypH2S with a pH-sensitive cyclic substructure for detection of acidic tumor microenvironment. Upon pH variation, the sensor underwent structural changes: the closed-ring form, CypH2S-C, exhibited suppressed dye aggregation, while the open-ring form, CypH2S-O, tended to aggregate in aqueous solutions under slightly acidic conditions. Importantly, CypH2S facilitated rapid and selective tumor visualization in a living mouse model via fluorescence imaging of its pH-responsive aggregation with a 1.9-fold tumor/background ratio less than 1 hour. Furthermore, prompt clearance of CypH2S from the bloodstream post-tumor detection. This work also pubished in the journal of Sensors and Actuators B: Chemical with a high evaluation.
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