Oxidative stress-responsive fluorescent polymer nanoplatform regulate lipid metabolism through lipophagy

Lipid droplets are dynamic organelles involved in lipid metabolism and various metabolic disorders. Herein, we report the design and synthesis of a novel amphiphilic polymer based on 18β-glycyrrhetinic acid (GA). GA was chemically conjugated to polyethylene glycol (PEG) and further functionalized with a lipid droplet-targeting fluorescent probe D via an oxalate ester bond, then self-assembly yielding PGOD nanoplatform. The PGOD were characterized by a uniform size of 135.6 ± 5.4 nm, a polydispersity index (PDI) of 0.23 ± 0.02, and a zeta potential of 11.81 ± 1.44 mV. These nanoparticles exhibited dual fluorescence properties driven by aggregation-induced emission (AIE) and excited-state intramolecular proton transfer (ESIPT). This work provided that nanoplatform could specifically label lipid droplets to monitor the progress of lipid accumulation, alleviating oxidative stress, and at the same time promote the decomposition of lipid droplets by activating lipophagy, significantly improving the lipid metabolism disorder in the liver of NAFLD model mice.