Nanodrug rescues liver fibrosis via synergistic therapy with H 2 O 2 depletion and Saikosaponin b1 sustained release.
Mengyun PengMeiyu ShaoHongyan DongXin HanMin HaoQiao YangQiang LyuDongxin TangZhe ShenKuilong WangHaodan KuangGang CaoPublished in: Communications biology (2023)
Hypoxia and hydrogen peroxide (H 2 O 2 ) 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 H 2 O 2 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 MnO 2 and anti-fibrosis Saikosaponin b1 (Ssb1) is subsequently constructed for antifibrotic therapy. MnO 2 catalyzes the accumulated H 2 O 2 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 MnO 2 @PLGA/Ssb1 nanosystem displays enhanced antifibrotic efficiency through removing excess H 2 O 2 and hypoxic stress, which may be a promising therapeutic approach for liver fibrosis treatment.
Keyphrases
- liver fibrosis
- hydrogen peroxide
- growth factor
- oxidative stress
- induced apoptosis
- end stage renal disease
- drug delivery
- transforming growth factor
- pulmonary fibrosis
- newly diagnosed
- chronic kidney disease
- ejection fraction
- nitric oxide
- cancer therapy
- wastewater treatment
- peritoneal dialysis
- dna damage
- endoplasmic reticulum stress
- prognostic factors
- ischemia reperfusion injury
- endothelial cells
- idiopathic pulmonary fibrosis
- systemic sclerosis
- cell cycle arrest
- type diabetes
- stem cells
- skeletal muscle
- patient reported outcomes
- adipose tissue
- mesenchymal stem cells
- cell proliferation
- anti inflammatory
- drug release