Visualization of Lung Inflammation to Pulmonary Fibrosis via Peroxynitrite Fluctuation

Area of Science:

• Biomedical Engineering
• Medical Diagnostics
• Pulmonary Medicine

Background:

• Idiopathic pulmonary fibrosis (IPF) is a severe lung disease with poor prognosis.
• Early diagnosis of IPF is challenging due to unknown causes and lack of noninvasive methods.
• Mitochondrial oxidative stress is implicated in the progression of pulmonary fibrosis.

Purpose of the Study:

• To develop a novel fluorescent probe for simultaneous detection in the near-infrared (NIR)-Ia window.
• To investigate the role of peroxynitrite (ONOO-) in various lung conditions, from healthy to fibrotic states.
• To evaluate the therapeutic efficacy of aminoguanidine hemisulfate salt (AG) in pulmonary fibrosis.

Main Methods:

• A ratiometric fluorescent probe, rTPONOO-1, with two-photon and mitochondria-targeting capabilities was synthesized.
• The probe was used to monitor ONOO- levels in lung slices representing different stages of fibrosis.
• Correlation between probe fluorescence and fibrosis severity (assessed by H&E and Masson staining) was analyzed.

Main Results:

• The ratiometric fluorescence changes of rTPONOO-1 showed a linear correlation with the progression rate of pulmonary fibrosis.
• The probe successfully visualized ONOO- levels in different lung states.
• The study demonstrated the potential of AG as a therapeutic agent.

Conclusions:

• The ratiometric fluorescent probe rTPONOO-1 is a promising tool for early IPF diagnosis and progression monitoring.
• rTPONOO-1 facilitates the study of peroxynitrite's role in lung fibrosis.
• The findings support the potential of rTPONOO-1 in guiding effective IPF treatment strategies.