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An Activatable NIR Fluorescent Rosol for Selectively Imaging Nitroreductase Activity.

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Area of Science:

  • Biomedical Engineering
  • Molecular Imaging
  • Cancer Diagnostics

Background:

  • Tumor hypoxia is a key factor in therapeutic resistance and cancer progression.
  • Current probes for hypoxia detection have limitations in photophysical properties.
  • Nitroreductase (NTR) activity is a biomarker for hypoxic tumor cells.

Purpose of the Study:

  • To design and develop a novel, activatable molecular probe for imaging hypoxic tumor cells.
  • To overcome the limitations of existing fluorogenic constructs for hypoxia detection.
  • To enable targeted cancer therapies and understand disease progression mechanisms.

Main Methods:

  • Rational design of an ultracompact xanthene core-based molecular probe (NO-Rosol).
  • Utilized Density Functional Theory (DFT) calculations for scaffold and moiety selection.
  • Evaluated probe's photophysical properties, selectivity, and fluorescence enhancement in solution and cell cultures.

Main Results:

  • NO-Rosol exhibits OFF-ON near-infrared (NIR) fluorescence (> 700 nm) with a large Stokes shift (> 150 nm).
  • Demonstrated selective imaging of NTR activity with 705 nm emission and 157 nm Stokes shift.
  • Achieved significant fluorescence enhancement (28-fold in solution, 12-fold in cells) due to NTR activity.

Conclusions:

  • NO-Rosol is the first activatable xanthene core-based probe for selective imaging of NTR activity in hypoxic environments.
  • The probe's design overcomes limitations of existing hypoxia imaging agents.
  • NO-Rosol shows promise for preclinical studies in providing favorable contrast for hypoxia detection.