A mitochondria-targeted nanozyme with enhanced antioxidant activity to prevent acute liver injury by remodeling mitochondria respiratory chain

Abstract

Developing nanomedicines with enhanced activity to scavenge reactive oxygen species (ROS) has emerged as a promising strategy for addressing ROS-associated diseases, such as drug-induced liver injury. However, designing nanozymes that not only remove ROS but also accelerate the repair of damaged liver cells remains challenging. Here, a two-pronged black phosphorus/Ceria nanozyme with mitochondria-targeting ability (TBP@CeO₂) is designed. TBP@CeO₂ nanozymes exhibit multienzyme activities and display significantly enhanced ROS scavenging capacity. They can effectively mitigate acetaminophen (APAP)-induced liver injury by scavenging excessive ROS and restoring mitochondrial complex II activity to promote energy-dependent liver cell repair. The in vitro experiments reveal that TBP@CeO₂ nanozymes can effectively eliminate ROS and restore mitochondrial function, thereby decreasing the cytotoxicity on BRL 3A cells exposed to APAP/H₂O₂. The in vivo studies show that TBP@CeO₂ nanozymes can improve the complex II activity and mitochondrial function in the liver, decreasing ROS and ensuring sufficient adenosine triphosphate (ATP) production, which helps protect the liver tissue against oxidative damage. This research introduces an innovative design strategy for nanozymes in the treatment of ROS-related diseases.