Dual detoxification and inflammatory regulation by ceria nanozymes for drug-induced liver injury therapy

Drug-induced liver injury (DILI) is the predominant cause of acute liver failure in many countries, which is closely associated with reactive oxygen species (ROS) and inflammation. Although N-acetylcysteine (NAC) is presently the first-choice antidote for DILI, it often fails to benefit the late stage patients due to its narrow therapeutic time window. Herein, we report ceria nanozymes (CeNZs) that simultaneously scavenge reactive oxygen species and generate oxygen for the treatment of acetaminophen-induced liver injury (a typical form of DILI), enabling a prolonged therapeutic time window as compared to NAC. It is found that CeNZs can effectively scavenge ROS in impaired hepatocytes for detoxification. More importantly, CeNZs can generate abundant oxygen based on their catalase (CAT)-mimic activity, thus further alleviating hypoxia and specifically inhibiting the pro-inflammatory macrophages to relieve inflammation for a promoted hepatocyte regeneration of DILI, which is vital for the treatment of late stage DILI when there is already massive hepatocyte necrosis. The dual detoxification and inflammatory regulation by CeNZs for DILI treatment with relatively long therapeutic time window as compared to NAC, together with the revealed mechanism herein, suggesting the future clinical use of CeNZs for DILI treatment, especially for the late stage DILI treatment.