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Design of a NIR-I Viscosity-Sensitive Fluorescent Probe for Tracking Nuclear Physiological Changes During Different
Jiaying Yu1, Hao Zhang1, Shen Yuan2
1Department of Central Laboratory, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Northern Jiangsu Institute of Clinical Medicine, Nanjing Medical University, Huai'an 223300, Jiangsu Province, China.
Analytical Chemistry
|January 5, 2026
Summary
We developed YY-2, a novel fluorescent probe for live-cell nuclear tracking. This probe offers rapid, low-toxicity nuclear staining and enables detailed visualization of cellular structures and dynamics.
Area of Science:
- Chemical Biology
- Molecular Imaging
- Biochemistry
Background:
- Organic small-molecule fluorescent probes are vital for cellular imaging.
- Existing probes may have limitations in toxicity or staining efficiency.
Purpose of the Study:
- To design and evaluate a novel viscosity-sensitive fluorescent probe, YY-2, for live-cell nuclear tracking.
- To investigate the intermolecular interactions and computational properties of YY-2 for DNA binding.
Main Methods:
- Design and synthesis of the YY-2 probe.
- Computational analysis including electrostatic potential (ESP) and DNA binding energy calculations.
- Live-cell imaging experiments with various cell types (KYSE150, SiHa).
Main Results:
- YY-2 demonstrated efficient live-cell nuclear staining within 15 min at 0.2 μM in a wash-free manner.
- The probe exhibits favorable DNA binding energy and lower toxicity compared to Hoechst 33342.
- YY-2 enabled discrimination of nuclear substructures and spatiotemporal monitoring of nuclear changes.
Conclusions:
- YY-2 is a promising fluorescent probe for live-cell nuclear tracking and imaging.
- Its design leverages intermolecular interactions for specific DNA binding and fluorescence turn-on.
- The probe facilitates detailed visualization of nuclear dynamics in various cell types.

