Dual-Color Visualization of Hepatic Fibrosis and Multidimensional Assessment of Therapeutic Drugs by a Multifunctional Single-Molecular Fluorescent Probe

Abstract

There is a high relevance between changes in ClO^– levels/mitochondrial morphology and the development of hepatic fibrosis; however, the efficient tools that are capable of real-time monitoring both of them and exploring their interrelations are extremely rare. Herein, we developed a multifunctional fluorescent probe based on a “three-in-one” strategy, named Mito-XS, which is firmly anchored in mitochondria, allowing for the ratiometric detection of ClO^– and the accurate analysis of mitochondrial morphology. Probe Mito-XS can sensitively capture the changes of ClO^– levels in mitochondria and successfully achieve simultaneous real-time monitoring of ClO^– levels and mitochondrial morphology during oxidative stress. Utilizing probe Mito-XS, the evaluations of three therapeutic drugs (silymarin, methyl ferulic acid, and puerarin) on protecting cells from CCl₄-induced damage were visualized by assessing their capabilities of inhibiting ClO^– levels and maintaining mitochondrial morphology. Furthermore, dual-color imaging in hepatic fibrosis mice models revealed the exacerbation of hepatic fibrosis, and the therapeutic effect of puerarin can be tracked by the fluctuation of ClO^– levels. Therefore, probe Mito-XS is an effective imaging tool to monitor mitochondrial morphology and ClO^– levels at the same time and has the potential to work as an evaluation tool to screen therapeutic drugs for hepatic fibrosis treatment.