Integrated cascade antioxidant nanozymes-Cu 5.4 O@CNDs combat acute liver injury by regulating retinol metabolism

作者：Jiayu Chen, Yujie Zhang, Zhichao Deng, Yuanyuan Zhu, Chenxi Xu, Bowen Gao, Wenlong Wang, Jie Xiao, Zhengtao Xiao, Mingzhen Zhang, Kangsheng Tu · 发表于：Theranostics · 年份：2025 · DOI：10.7150/thno.106811 · 被引用次数：8 · 研究领域：Advanced Nanomaterials in Catalysis、Nanoplatforms for cancer theranostics、Electrochemical sensors and biosensors

Background: Acute liver failure (ALF) represents a critical medical condition marked by the abrupt onset of hepatocyte damage, commonly induced by etiological factors such as hepatic ischemia/reperfusion injury (HIRI) and drug-induced hepatotoxicity.Across various types of liver injury, oxidative stress, heightened inflammatory responses, and dysregulated hepatic retinol metabolism are pivotal contributors, particularly in the context of excessive reactive oxygen species (ROS).Methods: C-dots were combined with Cu5.4O USNPs to synthesize a cost-effective nanozyme, Cu5.4O@CNDs, which mimics the activity of cascade enzymes.The in vitro evaluation demonstrated the ROS scavenging and anti-inflammatory capacity of Cu5.4O@CNDs.The therapeutic potential of Cu5.4O@CNDs was evaluated in vivo using mouse models of hepatic ischemia/reperfusion injury and LPS/D-GalN induced hepatitis, with transcriptome analysis conducted to clarify the mechanism underlying hepatoprotection.Results: The Cu5.4O@CNDs demonstrated superoxide dismutase (SOD) and catalase (CAT) enzyme activities, as well as hydroxyl radical (OH) scavenging capabilities, effectively mitigating ROS in vitro.Furthermore, the Cu5.4O@CNDs exhibited remarkable targeting efficacy towards inflammation cells induced by H2O2 and hepatic tissues in murine models of hepatitis, alongside exhibiting favorable biocompatibility in both in vitro and in vivo settings.Moreover, it has been demonstrated that Cu5.4O@CNDs effectively scavenged ROS...