Construction of dual-rotor-BODIPY-based fluorescent probes with improved sensitivity and brightness for lipid-droplet...

Lipid droplets (LDs) function as crucial organelles for intracellular lipid storage and their viscous vibrations are closely associated to metabolic disorders. However, existing fluorescent probes for viscosity are mainly constrained by relatively low sensitivity/brightness or weak lipid-droplet specificity. In this work, based on the one-rotor probe Bz-BDP with a meso-benzene, dual-rotor probes BT-BDP and BI-BDP utilized a benzothiazole or benzimidazole and a meso-benzene as two cooperative rotors. Remarkably, BT-BDP demonstrated superior fluorescence enhancements at 571 nm (946 folds) in glycerol compared to that in water, which was sufficiently higher than Bz-BDP at 531 nm (145 folds) and BI-BDP at 591 nm (190 folds). More interestingly, BT-BDP displayed excellent brightness in glycerol (Ф_F = 0.87). All these three probes exhibited good linear fluorescence enhancements for quantitatively monitoring the viscosity changes. Then, BT-BDP showed good targeting ability towards lipid droplets (R = 0.95) and successfully applied to monitor intracellular viscosity changes, which was further used to image LDs in liver tissues with deep tissue penetration (up to 21.2 μm) and high contrast. Therefore, we reported a successful example of dual rotor-BODIPY-based fluorescent probe BT-BDP for monitoring LDs-viscosity changes in cells and imaging LDs in tissues with improved sensitivity and brightness, proving a potential strategy for designing highly sensitive fluorescent rotors.