Trojan Horse-Like Biohybrid Nanozyme for Ameliorating Liver Ischemia-Reperfusion Injury

Liver ischemia and reperfusion (I/R) injury is a reactive oxygen species (ROS)-related disease that occurs during liver transplantation and resection and hinders postoperative liver function recovery. Current approaches to alleviate liver I/R injury have limited effectiveness due to the short circulation time, poor solubility, and severe side effects of conventional antioxidants and anti-inflammatory drugs. Herein, a universal strategy is proposed to fabricate a Trojan horse-like biohybrid nanozyme (THBN) with hepatic-targeting capabilities. Tannic acid (TA) mediates adeno-associated virus (AAV8) decoration onto 2D Ti₃C₂ nanosheets, resulting in THBN with a size of 116.2 ± 9.5 nm. Remarkably, THBN exhibits catalase (CAT)-like activity, broad-spectrum ROS scavenging activity and targeted delivery to liver tissue owing to the presence of AAV8. Both in vivo and in vitro experiments confirmed the efficacy of THBN in attenuating liver I/R injury by mitigating inflammation and oxidative stress and inhibiting hepatocellular apoptosis. RNA-seq analysis suggests that THBN may alleviate liver I/R injury by activating the PKC pathway. The effective targeting and therapeutic capabilities of THBN represent an advancement in nanotherapeutics for hepatic ischemia‒reperfusion injury, shedding light on the promising potential of this next-generation nanotherapeutic approach.