Mitochondrial-Targeting Near-Infrared Fluorescent Probe for Visualizing Viscosity in Drug-Induced Cells and a Fatty Liver Mouse Model

Abstract

Mitochondria, as “cell energy stations”, are involved in the regulation of various cell functions. Recent investigations revealed that mitochondrial dysfunction that can cause an intracellular viscosity mutation, a process that is associated with an increasing number of diseases that are not curable or manageable. However, conventional viscometers cannot be used to monitor the viscosity changes in living cells and in vivo. In order to cater to the complex biological environment, we present a chemical toolbox, MI-BP-CC, that employs N,N-diethyl and double bonds as sensitive sites for viscosity based on the TICT mechanism (twisted intramolecular charge transfer) to monitor the viscosity of living cells and fatter liver mice. MI-BP-CC features good mitochondrial targeting and a near-infrared emission. Surprisingly, in the presence of viscosity, the MI-BP-CC probe exhibited an ultrasensitive model for viscosity detection showing a red fluorescence signal from a silent “off” state to “on”. More importantly, utilizing the satisfactory detection performance of MI-BP-CC, we have successfully visualized increased viscosity under the pathological models of Parkinson’s (PD) and fatty liver mice. We anticipate that these findings will provide a convenient and efficient tool to understand physiological functions of viscosity in more biosystems.

Near-Infrared Probes for Biothiols (Cysteine, Homocysteine, and Glutathione): A Comprehensive Review

“…Coumarin derivatives are often used for the detection of small analytes, and due to their highly fluorescent nature and photostability, their applications were studied in biological samples via cell imaging. − Feng et al have synthesized and reported NIR-42 , which behaved both as a colorimetric and fluorescent sensor for the detection of Cys in PBS/DMSO (9:1, v/v) through the ICT effect. With Cys, NIR-42 showed a yellow to purple colorimetric change, easily detected by naked eye.…”

Mitochondrial Membrane Potential Independent Near-Infrared Mitochondrial Viscosity Probes for Real-Time Tracking Mitophagy

“…A striking feature of mitophagy is an altered mitochondrial microenvironment. Mitochondrial viscosity, a key index of the mitochondrion microenvironment, is intimately associated with mitochondrial status and affects the interaction between biological signal molecules and chemical substances. − Abnormal viscosity of the mitochondrial matrix may influence the diffusion of metabolites, which has been implicated in several cellular diseases such as cellular malignancies, atherosclerosis, and diabetes, etc. − Therefore, monitoring the local viscosity changes of mitochondria, especially the viscosity changes related to mitophagy, is of great significance to the study of mitophagy. , Traditional viscometry methods, including capillary viscometer, falling ball viscometer, and rotational viscometer, are difficult to measure at the cellular level for the reason of designing for macroscopic fluids. , In contrast, the fluorescence probe method has been proven to be an indispensable method for tracking biomolecules and microenvironmental states due to its high sensitivity, non-invasiveness, and good temporal and spatial resolution. − …”

Dihydroxanthene-Based Near-infrared Fluorescent Probes for Monitoring Mitochondrial Viscosity in Living Cells and Mice

“…Aberrant mitochondrial viscosity correlates with neurodegenerative diseases, atherosclerosis, and diabetes. , Thus, monitoring mitochondrial viscosity variations is essential for understanding a variety of mitochondria-related cellular events. Although numerous fluorescent probes have been developed for monitoring mitochondrial viscosity, − most of them are still incapable of permanent immobilization on mitochondria and have other limitations, such as low response multiple, short emission wavelength, and high background fluorescence. Therefore, it is very challenging to develop mitochondria-immobilized near-infrared probes for the real-time monitoring of mitochondrial viscosity.…”