Glucose-Modified Viscosity-Responsive Turn-On Fluorescence Molecular Rotors for Wash-Free Live-Cell Imaging

Area of Science:

• Biochemistry
• Molecular Biology
• Cancer Research

Background:

• Overexpression of glucose transporters (GLUTs) is a hallmark of cancer cells, making them a key diagnostic target.
• Current imaging agents like 2-NBDG have limitations, including low brightness and the need for high concentrations and washing steps.

Purpose of the Study:

• To develop novel, bright, wash-free fluorescent probes for GLUT-mediated imaging of prostate cancer cells.
• To utilize viscosity-sensitive fluorophores to create "turn-on" imaging capabilities.

Main Methods:

• Synthesis of fluorescent molecular rotors (FMRs) based on the DMAB core with structural modifications like julolidine incorporation.
• Conjugation of DMAB-based fluorophores to glucose or glucosamine to create GLUT-targeted probes.
• Evaluation of probe performance in PC-3 prostate cancer cells, including wash-free imaging, inhibition studies, and comparison with 2-NBDG.

Main Results:

• Modified FMRs, particularly Julo-Ph, exhibited enhanced fluorescence quantum yields and viscosity sensitivity.
• The glucosamine conjugate, GlcN-Julo-Ph, enabled bright, wash-free fluorescence imaging of PC-3 cells.
• GlcN-Julo-Ph demonstrated superior performance over 2-NBDG, showing brighter intracellular fluorescence at lower concentrations without washing.

Conclusions:

• Viscosity-sensitive FMRs are effective for designing "turn-on" imaging probes.
• GlcN-Julo-Ph provides a promising platform for rapid, low-background detection of cancer cells via GLUT imaging.