鉄イオンによるオキシム切断に基づく蛍光センサーによるリソソーム内鉄代謝機構の解明

使用基于铁离子肟裂解的荧光传感器阐明溶酶体中的铁代谢机制

• 批准号: 20J15123
• 负责人: Mu Huiying
• 金额: $ 1.09万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2020
• 资助国家: 日本
• 起止时间: 2020-04-24 至 2022-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-20J15123/
• 关键词: fluorescent probe; pH-responsive; hemicyanine dye; living cells; reaction-based probes

In the year of PD researcher (R3), Huiying Mu's 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 small molecules. Compared with cyanine dyes in her previous research, the hemicyanine dyes have advantages in easy functionalization and short synthesis procedures. Therefore, a series of pH-responsive hemicyanine dyes were developed trough simple synthesized route to introduce the substitutions with varied electron donating ability. After evaluated their photophysical properties, she found that these sensors exhibited tunable absorption and emission wavelength, stokes shift, and pH-responsiveness depend on the substitutions. Among them, the sensor containing morphorine functional group as a lysosome targeting moiety showed optimized pKa value (6.2) for selectively subcellular organelle imaging in living cells. Furthermore, this sensor showed good reversibility for the detection of pH fluctuation under the stimulations under biological systems. The further research of this work will be continued for new applications in vivo.Besides,the authors' reasearch also foucused on the development of Fe(II)-responsive fluorescent probes, and this project will be continued in the future.

在PD研究员年(R3)，穆慧英的研究还集中在设计和合成新型基于反应的功能荧光传感器，以检测生物标本中与疾病相关的微小变化，如pH和小分子。与她之前研究的菁染料相比，半花菁染料具有官能化容易和合成步骤短的优点。因此，通过简单的合成路线开发了一系列pH响应型半花菁染料，以引入具有不同给电子能力的取代基。在评估了它们的光物理性质后，她发现这些传感器具有可调的吸收和发射波长、斯托克斯位移和pH响应性，取决于取代基。其中，含有吗啡官能团作为溶酶体靶向部分的传感器在活细胞中显示出最佳的pKa值(6.2)，用于选择性亚细胞细胞器成像。此外，该传感器对生物系统刺激下的pH波动检测具有良好的可逆性。这项工作的进一步研究将继续在活体中的新应用。此外，作者的研究也集中在Fe(II)响应型荧光探针的开发上，该项目将在未来继续进行。

项目成果

Dual-Stimuli-Responsive Probes for Detection of Ovarian Cancer Cells and Quantification of Both pH and Enzyme Activity

• DOI: 10.1246/bcsj.20210168
• 发表时间: 2021-06
• 期刊: Bulletin of the Chemical Society of Japan
• 影响因子: 4
• 作者: Wenting Huo;K. Miki;D. Tokunaga;Huiying Mu;Masahiro Oe;H. Harada;K. Ohe

pH-Activatable Cyanine Dyes for Selective Tumor Imaging Using Near-Infrared Fluorescence and Photoacoustic Modalities

• DOI: 10.1021/acssensors.0c01926
• 发表时间: 2021-01-22
• 期刊: ACS SENSORS
• 影响因子: 8.9
• 作者: Mu, Huiying;Miki, Koji;Ohe, Kouichi
• 通讯作者: Ohe, Kouichi

pH-activatable cyanine dyes for selective tumor imaging using near-infrared fluorescence and pgotoacoustic modalities

pH 可激活花青染料，用于使用近红外荧光和 pgotoacoustic 模式进行选择性肿瘤成像

• 发表时间: 2021
• 作者: Huiying Mu;Koji Miki;and Kouichi Ohe
• 通讯作者: and Kouichi Ohe

MMP-2-Activatable Photoacoustic Tumor Imaging Probes Based on Al- and Si-Naphthalocyanines

• DOI: 10.1021/acs.bioconjchem.1c00266
• 发表时间: 2021-06-25
• 期刊: BIOCONJUGATE CHEMISTRY
• 影响因子: 4.7
• 作者: Miki, Koji;Imaizumi, Naoto;Ohe, Kouichi
• 通讯作者: Ohe, Kouichi