Valence Engineering Driven Multiple Mechanisms of Superior Antioxidant Nanosheets for Treatment of Pulmonary Fibrosis

Abstract

Idiopathic pulmonary fibrosis is a chronic and highly lethal lung disease that largely associated with oxidative stress. Unfortunately, there is currently no effective antioxidant therapy targeting oxidative stress pathogenesis. One key and great challenge is finding ideal antioxidant materials with superior anti-fibrotic effects. In this study, we report novel antioxidant V4C3 nanosheets (V4C3 NSs) for treatment of pulmonary fibrosis by scavenging reactive oxygen and nitrogen species. It is found that the subtle auto-oxidation can adjust the valence composition of V4C3 NSs and prominently improve their antioxidant behavior. The valence engineering triggers the multiple antioxidant mechanisms of electron transfer, H atom transfer and enzyme like catalysis, thus endowing V4C3 NSs with broad-spectrum, high-efficiency and persistent antioxidant capacity. Benefiting from the super antioxidant properties and high biocompatibility, V4C3 NSs can significantly prevent myofibroblast proliferation and extracellular matrix abnormality, thus alleviating the progression of pulmonary fibrosis by ROS scavenging, anti-inflammation and rebuilding antioxidant defenses in the bleomycin-induced animal model. This study not only provides an important strategy for designing excellent antioxidant nanomaterials, but also proposes a nanoscheme for the treatment of pulmonary fibrosis and other oxidative stress-related diseases.