Engineering red-emissive carbon dots for monitoring lysosomal polarity in living cells and zebrafish

Lysosomal polarity is an essential microenvironment parameter in biological systems that is intimately associated to a wide range of cellular statuses. Monitoring polarity fluctuations in lysosomes is extremely meaningful for investigating lysosome-related diseases. Herein, we reported the de novo design and one-step synthesis of lysosome-targeted, red-emissive carbon dots (Lyso-CDs) using Nile Blue A, 3-nitrophenylboronic acid, and 4-morpholinoaniline as precursors, thereby endowing the CDs with abundant electron-donating groups and electron-withdrawing groups on the surface. Specifically, Lyso-CDs showed a high sensitivity to polarity owing to the formation of effective intramolecular charge-transfer (ICT) systems, with fluorescence intensity exhibiting a linear relationship against polarity (R2 = 0.9934). By virtue of the advantages, including rapid staining, outstanding biocompatibility, and strong lysosome binding ability, the Lyso-CDs have been applied in imaging the lysosomal polarity changes in cells and zebrafish induced by drugs. Moreover, lysosomal polarity was found to be lower in cancer cells than in healthy cells. Additionally, the Lyso-CDs were effectively applied to track the changes of lysosomal polarity during the autophagy process. More importantly, a gradually increasing trend in lysosomal polarity was demonstrated at zebrafish embryonic development. This work will provide a significant strategy for the design of fluorescent carbon dots in terms of structure and functionality, consequently further promoting the study on lysosome-related diseases.