Polarity-responsive N/S-codoped carbon dots for single-lipid-droplet analysis under metabolic perturbations.

Lipid droplets (LDs) undergo remodeling of their polarity microenvironment during abnormalities in lipid metabolism, accompanied by changes in LD abundance and size. However, the narrow ranges of polarity response, insufficient targeting specificity, and limited stability of existing probes hinder the dynamic and accurate monitoring of individual LDs. Here, we developed nitrogen and sulfur codoped carbon dots (NSCDs) for monitoring polarity-related microenvironmental responses of individual LDs under metabolic perturbations. NSCDs exhibited a solvent-dependent decrease in fluorescence intensity and an approximately 80 nm red shift in emission. NSCDs were rapidly internalized and preferentially localized in LDs. Nutrient deprivation and inhibition of triacylglycerol synthesis decreased area-normalized NSCDs fluorescence, whereas OA-induced lipid accumulation increased it, reflecting distinct polarity-related microenvironmental responses. Furthermore, time-lapse imaging captured local events resembling LD fusion during SR59230A treatment, accompanied by enhanced local fluorescence during these remodeling events. These results support the use of NSCDs for dynamically monitoring polarity-related microenvironmental responses of individual LDs under metabolic perturbations.