Mitochondria-targeting probes with large Stokes shift for detecting Amyloid-β and cellular viscosity changes

Area of Science:

• Biomedical Imaging
• Molecular Probes
• Neuroscience

Background:

• Pathological accumulation of amyloid-beta (Aβ) is linked to increased mitochondrial viscosity.
• Effective in vivo imaging probes require deep tissue penetration, high sensitivity, and specificity.
• Developing red-shifted theranostic agents with enhanced mitochondrial targeting is crucial for early disease diagnosis.

Purpose of the Study:

• To design and synthesize novel M-series fluorescent probes (M13–M15) for enhanced mitochondrial viscosity monitoring.
• To investigate the photophysical properties and Aβ aggregate interactions of the M-series probes.
• To evaluate the probes' efficacy in early diagnosis and treatment of Alzheimer's disease (AD).

Main Methods:

• Rational design of M-series probes based on Q-series compounds, incorporating a quinoline moiety to enhance intramolecular charge transfer (ICT).
• Characterization of photophysical properties, including absorption/emission wavelengths and Stokes shift, in DMSO.
• Evaluation of probe response to Aβ aggregates and assessment of mitochondrial targeting efficiency and viscosity monitoring in HeLa cells.

Main Results:

• M-series probes exhibited red-shifted absorption and emission, with M13 showing an 806 nm emission and a 266 nm Stokes shift in DMSO.
• The probes demonstrated effective monitoring of mitochondrial viscosity variations in cells.
• M14 achieved a high colocalization coefficient of 0.89 with a commercial mitochondrial dye, indicating strong mitochondrial targeting in HeLa cells.

Conclusions:

• The M-series fluorescent probes possess favorable photophysical properties and excellent mitochondrial targeting capabilities.
• These probes can effectively monitor changes in mitochondrial viscosity, a potential biomarker for Alzheimer's disease.
• The developed probes show significant potential for the early diagnosis and therapeutic strategies for Alzheimer's disease.