Abstract

Drug-induced liver injury (DILI) is a major cause of acute liver failure worldwide, with limited therapeutic options available. This condition progresses through a complex cascade involving oxidative stress, inflammation, and a failure to regenerate damaged tissue. To tackle these interconnected challenges, we developed an integrated biomimetic nanoplatform that synergistically combined rhodium nanozymes (Rhzymes) with mesenchymal stem cell-derived extracellular vesicle mimetics (MEMs). The Rhzymes provided potent multi-antioxidant activity by scavenging reactive oxygen and nitrogen species (ROS/RNS), thereby alleviating oxidative damage and inflammatory responses. Meanwhile, the MEMs functioned as smart delivery carriers with a natural affinity for the damaged liver. They enhanced the accumulation of the therapeutic cargo at the injury site and independently contribute to healing by promoting tissue repair and regeneration. Through this synergistic collaboration, the Rh@MEMs system not only improved targeted delivery to the damaged liver but also resolved the key pathological factors of DILI-oxidative damage, inflammation, and inadequate regeneration. As a result, the Rh@MEMs platform demonstrated significantly enhanced therapeutic efficacy against DILI both in vitro and in vivo . This study highlights the promise of synergistic nanozyme-biomimetic vesicle integration, as a multifunctional strategy for the treatment of DILI.