A Rhodol-Based Fluorescent Probe With Spirocyclic Ring Open-Close Tunability for Sensitive Tracking of Lysosomal...

Area of Science:

• Cell Biology
• Biochemistry
• Molecular Imaging

Background:

• Subcellular organelle polarity is crucial for biological and pathological processes.
• Lysosomes, key organelles, require accurate polarity sensing for disease mechanism studies.
• Existing methods lack specificity or efficiency in monitoring lysosomal polarity in vivo.

Purpose of the Study:

• To develop a novel fluorescent probe for sensitive and specific detection of lysosomal polarity.
• To investigate the role of lysosomal polarity in cellular senescence and cancer.
• To establish a correlation between lysosomal polarity and cellular physiological states.

Main Methods:

• Design and synthesis of ROMO, a rhodol-based, morpholine-containing fluorescent probe.
• Characterization of ROMO's response to environmental polarity using spectroscopy.
• Application of ROMO for real-time monitoring of lysosomal polarity in living cells (young, senescent, healthy, and cancerous) using fluorescence microscopy.

Main Results:

• ROMO exhibits a tunable spirocyclic structure that opens/closes based on polarity, converting from nonfluorescent to red-emitting.
• A linear correlation was observed between ROMO's fluorescence intensity and solvent polarity.
• Lysosomal polarity was significantly higher in healthy cells than in cancer cells and increased with cellular senescence.

Conclusions:

• ROMO is an effective tool for monitoring lysosomal polarity in living cells.
• Lysosomal polarity serves as a potential biomarker for distinguishing healthy from cancerous cells.
• Lysosomal polarity changes are linked to cellular senescence progression.