Mitochondria-Targeted Chemosensor to Discriminately and Continuously Visualize HClO and H2S with Multiresponse Fluorescence Signals for In Vitro and In Vivo Bioimaging

Abstract

Bioactive molecules play a vital role in the process of regulating the redox balance in the intracellular environment, especially in maintaining the function of organelles. To explore the association and function of bioactive molecules in organelles, it is essential to develop a chemosensor tool that uses multiresponse fluorescence signals to distinguish between and track two related bioactive molecules in organelles. However, the development of sensors with multiresponse functions is still a challenging task. Herein, we present a unique and practical single chemosensor (Mito-CTC) that can monitor HClO (as an oxidative substance) and H2S (as a reductive substance) in mitochondria (organelle targeting) with multiresponse fluorescence signals. The response of the sensor to HClO and H2S changes from red to green and blue channel emission simultaneously, respectively, thereby providing a specific signal response to reductive/oxidative substances in the mitochondria. Using a single chemosensor, we have realized multichannel bioimaging of the exogenous and endogenous HClO and H2S in cellular mitochondria. Additionally, the excellent properties of the sensor Mito-CTC can be used to reveal the relationship between HClO and H2S in mitochondria. Meanwhile, Mito-CTC has been endowed with the ability to image in bacteria and zebrafish attributed to the good permeability and low cytotoxicity. Expectantly, drug-induced liver injury (DILI) caused by fluoxetine (an antidepressant drug) and the degree of drug-induced toxicity to the liver were evaluated using Mito-CTC through discriminating and imaging HClO, indicating that Mito-CTC has the potential function of evaluating the toxicity of the drug to the liver.