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Mitochondrial-Targeted Ratiometric Near-Infrared Fluorescence Probe for Monitoring Nitric Oxide in Rheumatoid

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A new fluorescent probe, NFL-NH2, effectively visualizes nitric oxide (NO) in rheumatoid arthritis (RA). This mitochondrial-targeted probe aids in early RA diagnosis by tracking NO levels in cells and live mice models.

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Area of Science:

  • Biomedical Engineering
  • Chemical Biology
  • Medical Diagnostics

Background:

  • Rheumatoid arthritis (RA) is an autoimmune disease where nitric oxide (NO) plays a key role in inflammation.
  • Accurate assessment of NO levels is crucial for understanding RA pathology and progression.

Purpose of the Study:

  • To develop a novel mitochondrial-targeted, near-infrared fluorescent probe (NFL-NH2) for visualizing and quantifying NO in RA.
  • To assess the probe's efficacy in detecting NO in cellular and animal models of RA.

Main Methods:

  • Synthesis of NFL-NH2 probe utilizing intramolecular charge transfer.
  • Evaluation of probe's response to NO, including sensitivity and detection limit.
  • Testing probe's mitochondrial targeting and NO detection in RAW 264.7 cells.
  • Application of the probe for in vivo ratiometric fluorescence imaging in RA mouse models.

Main Results:

  • NFL-NH2 exhibited a significant 44-fold fluorescence intensity ratio change in response to NO, with a low detection limit of 0.536 nM.
  • The probe demonstrated accurate mitochondrial targeting and sensitive detection of both exogenous and endogenous NO in cellular assays.
  • In vivo imaging revealed NFL-NH2's ability to rapidly detect NO levels correlated with inflammatory damage in RA mouse models.

Conclusions:

  • NFL-NH2 is a highly sensitive and specific fluorescent probe for NO detection.
  • The probe facilitates real-time monitoring of NO dynamics in RA.
  • NFL-NH2 shows significant potential as a diagnostic tool for NO-mediated RA diseases.