ABSTRACT
Aberrant mitochondrial viscosity is closely associated with many diseases and cellular malfunctions. Thus, the development of reliable methods for monitoring mitochondrial viscosity variations has attracted considerable attention. Herein, through stepwise structural modulation of the dihydroxanthene fluorophore (DHX), we developed three NIR fluorescent probes, named DHX-V-1-3, for detecting mitochondrial viscosity. Among them, DHX-V-3 displayed the highest signal-to-noise ratio (67-fold) for viscosity with outstanding selectivity and showed excellent mitochondria targeting and immobilization ability. At the cellular level, the DHX-V-3 probe was successfully applied to image the mitochondrial viscosity in live cells upon treatment with lipopolysaccharide (LPS) or nystatin. Moreover, benefiting from its NIR emission and the increased depth of tissue imaging, DHX-V-3 demonstrated the ability to visualize the increased viscosity in LPS-treated mice.
Subject(s)
Fluorescent Dyes , Lipopolysaccharides , Humans , Animals , Mice , Fluorescent Dyes/chemistry , Viscosity , Lipopolysaccharides/pharmacology , Lipopolysaccharides/analysis , Mitochondria/chemistry , Microscopy, Fluorescence/methods , HeLa CellsABSTRACT
Herein, seven viscosity-sensitive probes were developed via simple structural modification of dicyanoisophorone (DCO)-derived dyes. Among them, DCO-5 significantly enhances (180-fold) the response signal in highly viscous aqueous media while showing insensitivity to polarity changes or pH variations, and enables the successful detection of viscosity changes in nystatin-treated HepG2 cells, PC 12 cells and zebrafish.
