A lysosome-targetable near infrared fluorescent probe for glutathione sensing and live-cell imaging

A novel near-infrared self-quenching dye SQSS consisting of two SQ fluorophores and a cystamine linker was constructed for the selective detection of GSH. Owing to the enhanced aggregation-caused quenching (ACQ) and FRET-mediated self-quenching effects, the background fluorescence intensity of SQSS is very weak, providing relatively high signal-to-noise ratio. The disulfide linker of SQSS can be selectively cleaved by glutathione (GSH) rather than other biothiols to produce two SQ derivatives through cooperative intermolecular hydrogen bonds and specific electrostatic interactions. The exclusive interaction of GSH with SQSS interrupt the FRET self-quenching effects between two SQ fluorophores, thereby generating a significant turn on spectral response for detection of GSH in near infrared region. Cell imaging experiments showed that SQSS can monitor endogenous and exogenous GSH in tumor or normal cells. More importantly, colocalization experiments indicated that SQSS mainly located in the lysosome, an organelle tightly associated with GSH functions. With the excellent membrane permeability and lysosome-specificity, it is convinced that SQSS will be a powerful tool in the future research on the function of GSH in lysosomes.