Nanodrug rescues liver fibrosis via synergistic therapy with H2O2 depletion and Saikosaponin b1 sustained release

Hypoxia and hydrogen peroxide (H₂O₂) accumulation form the profibrogenic liver environment, which involves fibrogenesis and chronic stimulation of hepatic stellate cells (HSCs). Catalase (CAT) is the major antioxidant Enzyme that catalyzes H₂O₂ into oxygen and water, which loses its activity in different liver diseases, especially in liver fibrosis. Clinical specimens of cirrhosis patients and liver fibrotic mice are collected in this work, and results show that CAT decrease is closely correlated with hypoxia-induced transforminmg growth factor β1 (TGF-β1). A multifunctional nanosystem combining CAT-like MnO₂ and anti-fibrosis Saikosaponin b1 (Ssb1) is subsequently constructed for antifibrotic therapy. MnO₂ catalyzes the accumulated H₂O₂ into oxygen, thereby ameliorating the hypoxic and oxidative stress to prevent activation of HSCs, and assists to enhance the antifibrotic pharmaceutical effect of Ssb1. This work suggests that TGF-β1 is responsible for the diminished CAT in liver fibrosis, and our designed MnO₂@PLGA/Ssb1 nanosystem displays enhanced antifibrotic efficiency through removing excess H₂O₂ and hypoxic stress, which may be a promising therapeutic approach for liver fibrosis treatment.