Hydrophilic polymeric fluorescent probes based on benzothiadiazole constructed for real-time monitoring of lipid droplet levels in cells.

Lipid droplets (LDs) are vital organelles that regulate neutral-lipid storage and metabolism, membrane architecture, and inter-membrane trafficking. Quantifying LD heterogeneity is essential for elucidating determinants of LD biogenesis and their roles in metabolic disorders and cancer. Here, we report a water-soluble polymeric probe, NBMA-co-PEGMA400, constructed by employing benzothiazole as the fluorescent core and hydrophilic PEGMA400 as the solubilizing segment via reversible addition-fragmentation chain-transfer (RAFT) polymerization. The probe exhibits pronounced solvatochromism, reflecting its sensitivity to environmental polarity. It rapidly penetrates cellular membranes and generates punctate, high-contrast fluorescence in both HeLa and HepG2 cells, achieving excellent co-localization with the commercial Nile Red dye (Pearson's coefficients: 0.91 and 0.80, respectively). These results establish NBMA-co-PEGMA400 as a robust fluorescent polymer for real-time biomonitoring of lipid droplets and highlight its potential for early disease diagnosis.