Idiopathic pulmonary fibrosis is a chronic and highly lethal lung disease that largely results from oxidative stress; however, effective antioxidant therapy by targeting oxidative stress pathogenesis is still lacking. The big challenge is to develop an ideal antioxidant material with superior antifibrotic effects. Herein, we report that V4C3 nanosheets (NSs) can serve as a potential antioxidant for treatment of pulmonary fibrosis by scavenging reactive oxygen and nitrogen species. Interestingly, subtle autoxidation can adjust the valence composition of V4C3 NSs and significantly improve their antioxidant behavior. Valence engineering triggers multiple antioxidant mechanisms including electron transfer, H atom transfer, and enzyme-like catalysis, thus endowing V4C3 NSs with broad-spectrum, high-efficiency, and persistent antioxidant capacity. Benefiting from antioxidant properties and good biocompatibility, V4C3 NSs can significantly prevent myofibroblast proliferation and extracellular matrix abnormality, thus alleviating the progression of bleomycin-induced pulmonary fibrosis in vivo by scavenging ROS, anti-inflammation, and rebuilding antioxidant defenses. This study not only provides an important strategy for designing excellent antioxidant nanomaterials, but also proposes a proof-of-concept demonstration for the treatment of pulmonary fibrosis and other oxidative stress-related diseases.
Keywords: V4C3 nanosheets; antioxidant; pulmonary fibrosis; reactive oxygen species; valence engineering.