GA receptor targeted chitosan oligosaccharide polymer nanoparticles improve non-alcoholic fatty liver disease by inhibiting ferroptosis.

Excessive iron in the liver may exacerbate Non-alcoholic fatty liver disease (NAFLD) by increasing the risk of liver cell expansion, inflammation and fibrosis. Ferroptosis in liver cells may lead the progression of simple fatty liver degeneration to steatohepatitis (NASH). More and more studies shew that ferroptosis played a crucial role in the pathological process of NAFLD. Based on the mechanism of ferroptosis, this study first synthesized a liver targeted 18-β-Glycyrrhetinic-acid-chitosan oligosaccharide -N-acetylcysteine polymer (GCNp), and further curcumin (Cur) was used as model drug to prepare Cur loaded nanodelivery system (GCNp-Cur NPs). The particle size of GCNp-Cur NPs was 132.5 ± 9.8 nm, PDI was 0.148 ± 0.026 and the potential was 23.8 mV. GCNp-Cur NPs can regulate the GPX4/GSH pathway, inhibit lipid peroxidation, restore cellular oxidative environment, reduce free Fe2+, improve cellular lipid metabolism and iron metabolism, thereby NPs inhibited liver cell ferroptosis through multiple pathways. Additionally, GCNp-Cur NPs could also alleviate liver tissue lipid accumulation and oxidative damage, delaying disease progression, and providing a new method and theoretical basis for the treatment of NAFLD.