Mitochondrial membrane potential-independent near-infrared fluorescent probes for viscosity-exclusive imaging

Area of Science:

• Biomedical Engineering
• Molecular Imaging
• Biochemistry

Background:

• Mitochondrial viscosity is a key indicator for early disease diagnosis.
• Existing fluorescent probes for mitochondrial viscosity are limited by dependence on mitochondrial membrane potential (MMP) and sensitivity to other microenvironmental factors.

Purpose of the Study:

• To develop a novel, mitochondria-targeting, MMP-independent, and viscosity-exclusive near-infrared (NIR) fluorescent probe.
• To establish a reliable tool for visualizing and quantifying mitochondrial viscosity changes in disease states.

Main Methods:

• Synthesis of ACR-DMA probe, incorporating a thiophene acetonitrile skeleton, pyridinium cation for mitochondrial targeting, and benzyl bromide for immobilization.
• Characterization of ACR-DMA's fluorescence properties, including sensitivity, selectivity, and "turn-on" behavior.
• In vitro and in vivo validation of ACR-DMA in monitoring viscosity changes induced by various agents and in disease models (tumors, inflammation, acute kidney injury).

Main Results:

• ACR-DMA exhibits high sensitivity to viscosity with a significant "turn-on" fluorescence response (>150-fold increase at 710 nm).
• The probe demonstrates firm mitochondrial immobilization and effective monitoring of viscosity fluctuations.
• Successful visualization of mitochondrial viscosity alterations in diverse disease contexts, including tumors, inflammation, and drug-induced acute kidney injury.

Conclusions:

• ACR-DMA is a robust and reliable fluorescent probe for assessing mitochondrial viscosity, overcoming limitations of previous methods.
• The probe's ability to detect viscosity changes in vitro and in vivo offers a promising avenue for early disease diagnosis.
• ACR-DMA holds potential for advancing the understanding and clinical diagnosis of mitochondrial viscosity-related pathologies.