A mitochondria-targeted fluorescent probe based on an anti-diffusion strategy for in situ imaging of fatty liver, inflammation and cancer.

Abnormal mitochondrial viscosity is closely associated with a wide range of diseases and cellular dysfunction. It is crucial to develop fluorescent probes for precisely monitoring changes of mitochondrial viscosity in the detection and treatment of associated diseases. However, mitochondria-targeted fluorescent probes currently faced off-target problems because their high water-solubility could hinder the accurate detection of mitochondrial viscosity. Herein, a viscosity-sensitive fluorescent probe, HPQ-MV was designed and synthesized in this work. The indole cation and HPQ (2-(2'-hydroxyphenyl)-4(3H)-quinazolinone) moiety were introduced could make the probe HPQ-MV have excellent mitochondrial targeting properties and reduce the aqueous solubility of HPQ-MV made the probe less susceptible to diffusion, respectively. When the mitochondrial membrane potential was decreased, HPQ-MV could remain stable in the mitochondria and not cause false-negative signals. HPQ-MV had a signal-to-noise ratio of up to 2900-fold with respect to viscosity which was unaffected by pH and polarity. Additionally, HPQ-MV possessed a tissue permeability of up to 62.6 μM and had effectively facilitated in vivo imaging of fatty liver, inflammation, and in situ tumors.