A multifunctional GLP-MnO₂ nanozyme suppresses TGF-β1/Smad signaling through ROS scavenging and dual-modality...

Liver fibrosis, characterized primarily by oxidative stress and excessive extracellular matrix deposition, represents a significant health burden. TGF-β1/Smad pathway activation serves as a central driver of this process. Unfortunately, current clinical treatments for liver fibrosis all have certain limitations, highlighting the urgency of developing novel therapeutic approaches. In this study, Ganoderma lucidum polysaccharide (GLP)-MnO₂ nanoenzymes primarily treat liver fibrosis through two mechanisms: first, it exhibits potent activity of antioxidant enzymes, such as catalase (CAT) and superoxide dismutase (SOD), successfully scavenging superoxide anion (·O₂^-), hydrogen peroxide (H₂O₂), and hydroxyl radicals (·OH) in fibrotic liver regions to alleviate oxidative stress. Second, it prevents the TGF-β1/Smad pathway from being activated. Consequently, fewer Collagen I, α-SMA, and inflammatory mediators TNF-α, IL-6, and IL-1β are produced. Additionally, this nanozyme exhibits passive liver targeting and dual-modality photoacoustic imaging (PAI) and magnetic resonance imaging (MRI) properties, providing crucial support for both therapeutic intervention and disease assessment in liver fibrosis. Collectively, these results show the therapeutic potential of GLP-MnO₂ nanozyme in treating liver fibrosis.