Quercetin-Loaded\nMelanin Nanoparticles Decorated with\nCollagenase Mediates Synergistic Immunomodulation and Restores Extracellular\nMatrix Homeostasis in Liver Fibrosis

Liver fibrosis is a chronic disease that lacks effective\ndrug treatment.\nChronic damage and inflammation lead to the formation of collagen\nand fibrous scars. However, the excessive accumulation of collagen\nI significantly hinders the delivery of drugs into liver tissue. Therefore,\nthis study developed a quercetin-loaded melanin nanoparticle codecorated\ncollagenase (MNP-QUE-COL) for the treatment of liver fibrosis. These\nresults showed that MNP-QUE-COL degraded excessive collagen I, thereby\nefficiently delivering melanin and quercetin into the liver tissue.\nMNP-QUE-COL exhibited optimal PA/MRI dual-mode imaging ability. In\naddition, the synergistic anti-inflammatory and reactive oxygen species\nscavenging function of quercetin and melanin was achieved by regulation\nof M1–M2 macrophage polarization and inhibition of pro-inflammatory\ncytokine release, reshaping the imbalanced extracellular interstitial\ninflammatory environment. The results of this research suggest that\nMNP-QUE-COL is a safe and efficient therapeutic nanoplatform for liver\nfibrosis, showing promise as a potential therapeutic strategy for\nliver fibrosis and associated diseases.