Liver Fibrosis Amelioration by Macrophage-Biomimetic Polydopamine Nanoparticles via Synergistically Alleviating Inflammation and Scavenging ROS.

The progression of liver fibrosis is determined by the interaction of damaged hepatocytes, active hepatic stellate cells, and macrophages, contributing to the development of oxidative stress and inflammatory environments within the liver. Unfortunately, the current pharmacological treatment for liver fibrosis is limited by its inability to regulate inflammation and oxidative stress concurrently. In this study, we developed a cell membrane biomaterial for the treatment of liver fibrosis, which we designated as PM. PM is a biomimetic nanomaterial constructed by encapsulating polydopamine (PDA) with a macrophage membrane (MM). It is hypothesized that PM nanoparticles (NPs) can successfully target the site of inflammation, simultaneously inhibit inflammation, and scavenge reactive oxygen species (ROS). In vitro experiments demonstrated that PM NPs exhibited strong antioxidant properties and the ability to neutralize pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β). Moreover, the capacity of PM NPs to safeguard cells from oxidative stress and their anti-inflammatory efficacy in an inflammatory model were validated in subsequent cellular experiments. Additionally, PM NPs exhibited a high biocompatibility. In a mouse model of hepatic fibrosis, PM NPs were observed to aggregate efficiently in the fibrotic liver, displaying excellent antioxidant and anti-inflammatory properties. Notably, PM NPs exhibited superior targeting, anti-inflammatory, and ROS scavenging abilities in inflamed tissues compared to MM, PDA, or erythrocyte membrane-encapsulated PDA. Under the synergistic effect of anti-inflammation and antioxidant, PM NPs produced significant therapeutic effects on liver fibrosis in mice. In conclusion, the synergistic alleviation of inflammation and ROS scavenging by this specially designed nanomaterial, PM NPs, provides valuable insights for the treatment of liver fibrosis and other inflammatory- or oxidative stress-related diseases.