Near-infrared ratiometric fluorescence imaging of lysosomal polarity in live cells and in vivo

A lysosome-targeted and polarity-specific NIR ratiometric response probe, DCM-ML, was established for linearly ratiometric imaging of lysosomal polarity in biosystems. [Display omitted] •A NIR probe DCM-ML was developed for ratiometric detection of lysosomal polarity.•Decreased polarity in apoptotic cells and cancer cells were found by DCM-ML staining.•Increased polarity in cells during autophagy process were found by DCM-ML staining.•Declining polarity in zebrafish development process was detected by DCM-ML staining. Lysosomal polarity changes have been reported to be able to reflect cell status in physiological and pathological processes, and may serve as a ubiquitous marker for cancer detection. Thus, to monitor polarity in lysosome is of great importance to distinguish abnormal cells in cell biology and oncologic pathology. Herein, a lysosome-targeted and near-infrared (NIR) emissive probe, named DCM-ML, was found to be highly sensitive toward polarity, with fluorescence intensity exhibiting a linearly ratiometric relationship (I655/I705) against polarity (Δf). The potential of DCM-ML for polarity detection has been successfully demonstrated in physiological and pathological processes in both cells and zebrafish. It was found that lysosomal polarity in cancer cells (HeLa, MCF-7 and HepG2) was lower than that in normal cells (LO2), and it would be gradually decreasing with the cell damage getting worse; while in contrast, lysosomal polarity increased gradually in autophagy process. Moreover, lysosomal polarity changes in zebrafish development were successfully monitored for the first time with the NIR ratiometric probe, which exhibited a gradually increasing trend during the development process. And polarity in live embryos and larvae was also found to be higher than that in dead ones. All the results demonstrate that DCM-ML has the potential application for cancer cell diagnosis, dead cell identification, and real-time monitoring of autophagy and zebrafish development processes by imaging of lysosomal polarity. The development of the probe should be helpful for studying lysosome-related physiological and pathological processes.