Multiplexing Nanodrug Ameliorates Liver Fibrosis via ROS Elimination and Inflammation Suppression.

Abstract

Liver fibrosis is the leading risk factor for hepatocellular carcinoma. Both oxidative stress and inflammation promote the progression of liver fibrosis, but existing therapeutic strategies tend to focus solely on one issue. Additionally, targeting of pathological microstructures is often neglected. Herein, an esterase-responsive carbon quantum dot-dexamethasone (CD-Dex) is developed for liver fibrosis therapy to simultaneously target pathological microstructures, scavenge reactive oxygen species (ROS), and suppress inflammation. Hepatocyte-targeting CD-Dex can efficiently eliminate the intrahepatic ROS, thereby inhibiting the activation of Kupffer cells, preventing further inflammation progression. Moreover, released dexamethasone (Dex) also suppresses inflammatory response by inhibiting the infiltration of inflammatory cells. Antifibrotic experiments demonstrate that CD-Dex significantly alleviates liver injury and collagen deposition, consequently preventing the progression of liver fibrosis. Taken together, these findings suggest that via ROS elimination and inflammation suppression, the newly developed multiplexing nanodrug exhibits great potential in liver fibrosis therapy.