Precisely activating ferroptosis by Fe(II)-triggered drug release for enhanced cancer therapy

通过 Fe(II) 触发药物释放精确激活铁死亡以增强癌症治疗

• 批准号: 22K20530
• 负责人: MU Huiying
• 金额: $ 1.83万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Research Activity Start-up
• 财政年份: 2022
• 资助国家: 日本
• 起止时间: 2022-08-31 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-22K20530/
• 关键词: iron(II); fluorescent probe; activatable; pH-responsive; cyanine dye; ferroptosis; fluorescent imaging; cancer therapy; bond cleavage

In the year of FY2022, the development and optimization of iron(II)-responsive drug release system in vitro was mainly conducted. Several oxime ester models were designed and synthesized. The stability and reactivity towards Fe2+ in aqueous solutions were evaluated. The proposed reaction mechanism and reaction product for the Fe2+-activated release were confirmed by ESI-MS spectra. Fluorescent cyanine dye and tumor-targeting moiety cRGD were synthesized by following the reported work of our research group.My research also focused on the design and synthesis of novel reaction-based functional fluorescent sensors to detect the diseases-related tiny changes in biological specimens such as pH, and enzymes. Due to the poor water-solubility and easily aggregation of cyanine dyes in aqueous solutions which hamper their biocompatibility in biological application. I am trying to develop the water-soluble Near-infrared pH-responsive cyanine dyes through introduction of several sulfonate groups to the benzoindole moiety of cyanine dyes. The dyes containing two or three anionic groups exhibited better water-solubility even in aqueous solutions without surfactant or organic solvents. Interestingly, I found that the aggregation nanoparticle size of dye in aqueous solutions was changed dependent on pH values which is promising to be used for the improved EPR effect for targeted and specific tumor imaging in vivo models.Besides, some cell experiments about enzyme-responsive probes for the cooperations with other researcher were conducted in this year.

于2022财政年度，本集团主要进行铁（II）响应性药物体外释放系统的开发及优化。设计并合成了几种肟酯模型物。评价了其在水溶液中的稳定性和对Fe 2+的反应性。通过ESI-MS光谱证实了Fe 2+激活释放的反应机理和反应产物。本课题组在前期工作的基础上，合成了荧光菁染料和肿瘤靶向基团cRGD，并设计合成了新型的基于反应的功能性荧光传感器，用于检测生物样品中与疾病相关的pH、酶等微小变化。由于菁染料水溶性差，在水溶液中易聚集，影响了其生物相容性。本论文试图通过在菁染料的苯并吲哚结构上引入磺酸基来开发水溶性的近红外pH响应菁染料。含两个或三个阴离子基团的染料在不含表面活性剂或有机溶剂的水溶液中也表现出较好的水溶性。有趣的是，我发现染料在水溶液中聚集的纳米颗粒大小随pH值的变化而变化，这有望用于改善EPR效应，用于靶向和特异性肿瘤体内成像模型。此外，今年与其他研究人员合作进行了一些酶响应探针的细胞实验。

项目成果

Photoacoustic Signal Enhancement of Al- and Si-Phthalocyanines Caused by Photoinduced Cleavage of Water-Soluble Axial Ligand

水溶性轴向配体光诱导断裂引起的铝和硅酞菁的光声信号增强

• DOI: 10.1016/j.jphotochem.2023.114547
• 发表时间: 2023
• 期刊: Journal of Photochemistry and Photobiology A: Chemistry
• 作者: Kohei Nogita;Koji Miki;Naoto Imaizumi;Masahiro Oe;Huiying Mu;and Kouichi Ohe
• 通讯作者: and Kouichi Ohe

アニオン性置換基を有する水溶性pH応答型シアニン色素の開発

具有阴离子取代基的水溶性pH响应型花青染料的开发

• 发表时间: 2023
• 作者: Shuai Shao;Huiying Mu;三木康嗣;大江浩一
• 通讯作者: 大江浩一

Steric Control in Activator-Induced Nucleophilic Quencher Detachment-Based Probes: High-Contrast Imaging of Aldehyde Dehydrogenase 1A1 in Cancer Stem Cells

• DOI: 10.1002/cplu.202200319
• 发表时间: 2022-11-01
• 期刊: CHEMPLUSCHEM
• 影响因子: 3.4
• 作者: Oe，Masahiro;Suzuki，Kanae;Ohe，Kouichi
• 通讯作者: Ohe，Kouichi