Dissecting Mitochondrial Sulfur Dioxide Generation Mechanism in Rheumatoid Arthritis with a NIR Luminogenic...

Area of Science:

• Biomedical Engineering
• Analytical Chemistry
• Mitochondrial Biology

Background:

• Sulfur dioxide (SO₂) is a vital mitochondrial antioxidant regulating redox homeostasis.
• Dysregulated mitochondrial SO₂ is implicated in rheumatoid arthritis (RA) pathogenesis.
• Existing SO₂ probes lack stability, sensitivity, and mitochondrial targeting for RA studies.

Purpose of the Study:

• To develop a near-infrared (NIR) luminescence probe for sensitive and real-time detection of mitochondrial SO₂.
• To investigate the role of SO₂ in RA pathogenesis using the developed probe.
• To explore SO₂ generation mechanisms in RA models.

Main Methods:

• Synthesis of an iridium(III) complex-based NIR probe utilizing a Michael addition mechanism.
• Detection of SO₂ in aqueous solutions and imaging of endogenous mitochondrial SO₂ in a cellular RA model.
• Visualization of aspartate aminotransferase 1 (AAT1)-mediated SO₂ generation and assessment of probe penetration in 3D tumor spheroids.

Main Results:

• The probe demonstrated sensitive SO₂ detection with a low limit of detection (2.12 μM).
• Successfully imaged mitochondrial SO₂ levels in a cellular RA model.
• Visualized AAT1-mediated SO₂ generation and showed excellent penetration (approx. 103 μm) in 3D tumor spheroids.

Conclusions:

• The developed NIR probe is a powerful tool for imaging subcellular SO₂ in RA.
• This probe enhances understanding of RA pathological mechanisms.
• It facilitates the development of advanced diagnostic tools for RA.