A near-infrared fluorescence probe with large Stokes shift for selectively monitoring nitroreductase in living cells...

Area of Science:

• Biomedical Engineering
• Chemical Biology
• Molecular Imaging

Background:

• Solid tumors often exhibit hypoxia due to insufficient oxygen supply.
• Nitroreductase (NTR) is overexpressed in solid tumors and serves as a biomarker for hypoxia.
• Efficient methods for assessing tumor hypoxia levels are highly desirable.

Purpose of the Study:

• To develop a novel near-infrared (NIR) fluorescence probe for monitoring NTR activity.
• To assess hypoxia levels in living cells and tumor-bearing models using the developed probe.
• To evaluate the probe's selectivity, sensitivity, and imaging capabilities.

Main Methods:

• Synthesis of a new NIR fluorescence probe (MR) with a "push-pull" structure.
• Investigation of the probe's response to NTR activity, involving reduction of a nitro-unit to an amino-moiety.
• Characterization of the probe's properties, including fluorescence signals, Stokes shift, selectivity, and limit of detection.
• Validation using cellular confocal fluorescence imaging and in vivo studies in tumor-bearing mice.

Main Results:

• The MR probe exhibited selective reduction by NTR, leading to prominent NIR fluorescence emission.
• The probe demonstrated intense NIR signals, a large Stokes shift, high selectivity, and a low limit of detection (46 ng/mL).
• MR successfully detected NTR levels in hypoxic cells and visualized elevated NTR in tumor-bearing mouse models.

Conclusions:

• The developed MR probe is an effective tool for monitoring NTR activity and assessing hypoxia levels.
• This NIR fluorescence-based platform offers a promising approach for real-time hypoxia detection in biological systems.
• The probe facilitates the visualization of hypoxia variations in tumors, aiding in cancer research and diagnostics.