Vanadium Carbide Nanosheets with Broad-Spectrum Antioxidant Activity for Pulmonary Fibrosis Therapy

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.