Nanozymes with Broad-Spectrum Scavenging of Reactive Oxygen Species (ROS) Alleviate Inflammation in Acute Liver Injury

Reactive oxygen species (ROS) related oxidative stress causes an inflammatory storm and massive hepatocyte necrosis in acute liver injury (ALI). Necrotic hepatocytes trigger an irreversible secondary injury mediated by the innate immune system, potentially leading to liver failure or even death. Therefore, antioxidant therapies may be hepatoprotective. Herein, we have reported novel metal-phenolic nanozymes (CA-Mn NPs) with broad-spectrum ROS scavenging ability. CA-Mn NPs inhibited hepatocyte apoptosis and prevented the recruitment of inflammatory monocytes through antioxidant mechanism in vitro. Meanwhile, CA-Mn NPs suppressed cell apoptosis and the levels of inflammatory factors in carbon tetrachloride (CCl4)-induced ALI mice. We further focused on the anti-inflammatory mechanisms of CA-Mn NPs and found that the Nrf2-Keap1 signaling pathway was upregulated and the NF-kappa B p65 pathway was downregulated. Besides, CA-Mn NPs restored the autophagic function and converted the M1 type macrophages to the M2 type. RNA sequencing also confirmed that CA-Mn NPs regulate the expression of apoptotic, autophagic, and inflammatory genes. Overall, the clearance of ROS by CA-Mn NPs prevented inflammation and apoptosis in ALI mice, providing new insights for the development of therapeutic strategies.