A nitroreductase-triggered NIR fluorescent probe for selective visualization in orthotopic breast cancer

Area of Science:

• Biomedical Imaging
• Chemical Biology
• Molecular Oncology

Background:

• Nitroreductase (NTR) is vital in hypoxic breast tumor metabolism, indicating aggressiveness and treatment outcomes.
• Existing probes for NTR visualization have limited photophysical properties, hindering accurate imaging.

Purpose of the Study:

• To develop a novel near-infrared (NIR) activatable fluorescent probe for visualizing nitroreductase (NTR) activity in breast cancer.
• To overcome the limitations of short emission wavelengths and small Stokes shifts in current probes.

Main Methods:

• Constructed DHM-NO2 by coupling the DHM-OH fluorophore with a nitrobenzyl recognition unit.
• Evaluated probe performance in vitro using breast cancer cells (MCF-7) and normal cells (MCF-10A).
• Assessed probe activation and tumor localization in an orthotopic breast cancer mouse model.

Main Results:

• DHM-NO2 exhibited negligible background fluorescence and rapid, NTR-mediated activation, releasing DHM-OH for NIR emission (880 nm).
• The probe demonstrated high sensitivity (25.6 pg/mL detection limit), selectivity, and resistance to ROS/RNS interference.
• Successfully differentiated cancer cells, responded to metabolic modulation, and produced tumor-localized fluorescence in vivo with high tumor-to-normal ratios.

Conclusions:

• DHM-NO2 is a sensitive and selective NIR-I fluorescent probe for monitoring NTR activity in breast cancer.
• The probe's design overcomes previous limitations, enabling effective imaging of tumor metabolism and therapeutic response.
• DHM-NO2 is compatible with standard fluorescence instrumentation, facilitating clinical translation.