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.

Progress and perspectives: fluorescent to long-lived emissive multifunctional probes for intracellular sensing and imaging

“…Apart from the development of multi-organelle targeting molecular probes, multi-analyte responsive probes have been employed to monitor the intracellular changes due to the different analyte levels under diverse pathophysiological conditions. 90,91 For example, the overexpression of HClO is known to cause oxidative stress in cells and is related to several neurodegenerative diseases. 90,92 However, H 2 S acts as an HClO inhibitor and reduces the chances of oxidative stress.…”

“…90,91 For example, the overexpression of HClO is known to cause oxidative stress in cells and is related to several neurodegenerative diseases. 90,92 However, H 2 S acts as an HClO inhibitor and reduces the chances of oxidative stress. Hence, the development of a probe to simultaneously detect the intracellular fluctuation of H 2 S and HClO is crucial to monitoring normal cellular functioning.…”

A NIR‐II Fluorescent Probe for Hydrogen Sulfide Detection Based on Blocking Intramolecular Charge Transfer

“…[4,5] Trace amounts of H 2 S exist in mammals to regulate the immune system, nerve conduction, vasodilation, energy metabolism, and oxidative stress response. [6][7][8] However, clinically, various diseases, such as cardiovascular disease, diabetes, down syndrome, cirrhosis, and Alzheimer's disease, are tightly correlated with the level of H 2 S. [9][10][11][12] Therefore, given the crucial roles of H 2 S in indicating human physiological activities and treatment efficacy, it is of profound significance to develop a noninvasive and rapid method for H 2 S detection. [13][14][15] To date, a variety of approaches have been developed to detect H 2 S, [16][17][18][19][20][21][22] including colorimetry, [23] electrochemical analysis, [24] gas chromatography, [25] metal sulfide precipitation, [26] among others.…”

A Simple ICT-Based Fluorescent Probe for HOCl and Bioimaging Applications

“…Nevertheless, fluorescence imaging technology has been became one of the most useful tools and it is widely used in chemical testing, biological analysis and medical research owing to its outstanding advantages such as high sensitivity, specific selectivity, and real-time non-invasiveness. At present, by means of the oxidation reactions, a series of organic small molecule fluorescence probes for ClO − detection have been established (the typical cases are displayed in Table S1) [14][15][16][17][18][19][20][21][22][23], including boron dipyrromethene, rhodamine, naphthalimide, triphenylamine, coumarin and nile red. Those dyes were modified with a variety of ClO − specific recognition sites to form the different kinds of organic small molecule fluorescent probes.…”