Viscosity is a fundamental property in biological systems, influencing organelle function and molecular diffusion. Abnormal viscosity is associated with diseases such as metabolic disorders, neurodegeneration, and cancer. Lysosomes, central to cellular degradation and recycling, are sensitive to viscosity changes, which can disrupt enzymatic activity and cellular homeostasis. Monitoring lysosomal viscosity provides essential information on lysosomal health, helping to uncover underlying mechanisms in various diseases. Recognizing the need for effective monitoring of lysosomal viscosity changes in living cells, we have developed a near-infrared (NIR) viscosity-responsive fluorescent probe, VFLyso, specifically designed for lysosomal targeting. Based on the twisted intramolecular charge transfer (TICT) mechanism, VFLyso exhibits strong NIR fluorescence, a fast response, and a notable fluorescence response to viscosity variations (F/F = 65.5-fold), along with excellent selectivity and stability under physiological conditions. Our studies demonstrated that VFLyso could accurately monitor lysosomal viscosity changes in both cell cultures and animal models, including zebrafish and mouse models of fatty liver. This work not only provides a powerful tool for real-time monitoring of lysosomal viscosity but also offers valuable insights into the role of viscosity in disease progression, paving the way for potential diagnostic applications in related disorders.
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Application of a near-infrared viscosity-responsive fluorescent probe for lysosomal targeting in fatty liver mice.
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Viscosity is a fundamental property in biological systems, influencing organelle function and molecular diffusion. Abnormal viscosity is associated with diseases such as metabolic disorders, neurodegeneration, and cancer. Lysosomes, central to cellular degradation and recycling, are sensitive to viscosity changes, which can disrupt enzymatic activity and cellular homeostasis.
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Department of Radiology, Changhai Hospital, Naval Medical University, Changhai Road 168, Shanghai 200433, China. Electronic address:
Background: Lysosomes, as an indispensable subcellular organelle have numerous physiological functions closely associated with HS and viscosity, and accurate assessment of HS/viscosity fluctuations in lysosomes is essential for gaining a comprehensive understanding of lysosome-related physiological activities and pathological processes. The previous single-response fluorescent probes for either HS or viscosity alone have the potential to generate "false positive" signals in a complex biological environment. In contrast, dual-locked probes can simultaneously respond to multiple targets simultaneously, which could effectively eliminate this defect.
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School of Chemistry and Chemical Engineering, Anhui University of Technology, Ma'anshan 243032, PR China. Electronic address:
Peroxynitrite (ONOO) and viscosity are critical indicators of lysosome functionality, intimately linked to numerous diseases' pathophysiological processes. Hence, creating reliable analytical techniques to observe fluctuations in lysosomal ONOO and viscosity is highly important. This study presents the development of a novel naphthalimide-based fluorescent probe, Nap-Cy, specifically designed to target lysosomes and simultaneously detect both ONOO and viscosity.
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School of Electronics and Information Engineering, Changshu Institute of Technology, Changshu 215500, PR China. Electronic address:
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Laboratoire des biomolécules, LBM, Département de chimie, École normale supérieure, PSL University, Sorbonne Université, CNRS, 75005, Paris, France.
Dipolar fluorescent molecular rotors (FMRs) are environmentally-sensitive fluorophores that can be used in bioimaging applications to sense local viscosity and polarity. Their sensitivity to viscosity can also be used for the fluorogenic labeling of biomolecules such as DNA or proteins. In particular, we have previously used FMRs to develop a series of tunable fluorogens targeting the self-labeling protein tag Halotag for wash-free protein imaging in live cells.
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