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Multi-organelle-targeting pH-dependent NIR fluorescent probe for lysosomal viscosity

Chinese Chemical Letters 2023年第3期34卷 378-382页

作者： Huili Wang Yishuo Sun Xuemei Lin Wei Feng Zhanxian Li Mingming Yu Green Catalysis Center and College of Chemistry Zhengzhou UniversityZhengzhou 450001China Department of Chemistry State Key Laboratory of Molecular Engineering of PolymersInstitutes of Biomedical Sciences&Collaborative Innovation Center of Chemistry for Energy MaterialsFudan UniversityShanghai 200433China

The normal operation of lysosome, mitochondria, Golgi apparatus and endoplasmic reticulum plays a significant role in maintaining cell homeostasis. Reflecting the state and function of lysosomes, viscosity is a pivotal parameter to assess the stability of microenvironment. Herein, based on TICT mechanism,a new NIR pH-dependent fluorescent probe DCIC with push-pull electronic moiety was synthesized to identify the lysosomes viscosity. In viscous media, DCIC was highly sensitive to viscosity, fluorescence intensity increased by 180 times as viscosity increased from 1.0 cp to 438.4 cp. In addition, DCIC have high localization ability for lysosome, mitochondria, Golgi apparatus, and endoplasmic reticulum and can monitor lysosomal viscosity fluctuations with laser confocal microscopy.

关键词： NIR lysosomal viscosity PH-dependent Multi-organelle localization

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A lysosome-targeting dual-functional fluorescent probe for imaging intracellular viscosity and beta-amyloid

A lysosome-targeting dual-functional fluorescent probe for i...

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第十一届全国化学生物学学术会议

作者： Jinsheng Liu Hui-ya Tan Jinwu Yan School of Biology and Biological Engineering South China University of Technology

A lysosome-targeting dual-functional fluorescent probe was rationally designed and developed for imaging intracellular lysosomal viscosity and beta-amyloid. Neutral merocyanine dye（MC-1） was selected as the fluorophore to design probe Lyso-MC, In our study, a 3-morpholinopropylamine moiety was rationally introduced as an electron-donor to enhance the π electron conjugation so as to improve the fluorescence quantum yield, and function as a lysosomal targeting group. Lyso-MC exhibited an excellent linear relationship between the logarithm of fluorescence intensity and the logarithm of viscosity（R2 = 0.99, x = 0.53）. Meanwhile, the probe also showed a significant turn-on fluorescence response when bound to Aβ aggregates and a high sensitivity towards Aβ aggregates（detection limit: 10.2 nM）. Besides this, Lyso-MC was applied to monitor lysosomal viscosity changes and detect intracellular Aβ aggregates. More importantly, the real-time tracking of the dynamic movement of lysosomes, as vesicle structures, was achieved using Lyso-MC. Taking advantage of its remarkable properties, this versatile probe could be a promising imaging tool for use in Alzheimer’s disease pathology-related fields.

关键词： dual-functional fluorescent probe lysosomal viscosity beta-amyloid

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A novel Fluorescent Protein Chromophore Analogue to simultaneously probe lysosome viscosity and β-Amyloid fibrils

A novel Fluorescent Protein Chromophore Analogue to simultan...

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第十一届全国化学生物学学术会议

作者： Han Sun Hua-xiang Leng Jin-sheng Liu Jin-wu Yan School of Biology and Biological Engineering South China University of Technology

Alzheimer’s disease（AD） is an incurable neurodegenerative disease. To improve the diagnostic level of AD is essential to early treatment and effectively utilizes disease-modifying drugs. The amyloid cascade hypothesis and its revised version identify insoluble β-amyloid deposition as a good diagnostic biomarker for AD. We hypothesized that lysosomal viscosity may be an auxiliary biomarker for AD based on literature research. Herein, we have successfully developed the FP chromophore analogue C25 as a dual-functional fluorescent probe which respond to Aβ fibrils and viscosity in lysosome with distinguishable turn-on fluorescence signals around 570 nm and 600 nm, respectively. The probe C25 can also monitor the process of digesting Aβ in lysosome. The probe C25 can serve as a promising tool for developing the early diagnosis and innovative therapeutics of AD.

关键词： Alzheimer’s Disease Aβ fibrils lysosomal viscosity dual-functional fluorescent probe FP chromophore

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