Gao Xin, Yang Xinjian, Deng Chunlin, Chen Yaxiao, Bian Yueying, Zhang Xinyu, Jin Yi, Zhang Jinchao, Liang Xing-Jie
Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, College of Chemistry & Materials Science, State Key Laboratory of New Pharmaceutical Preparations and Excipients, Chemical Biology Key Laboratory of Hebei Province, Hebei University, Baoding 071002, PR China.
Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, College of Chemistry & Materials Science, State Key Laboratory of New Pharmaceutical Preparations and Excipients, Chemical Biology Key Laboratory of Hebei Province, Hebei University, Baoding 071002, PR China.
Biomaterials. 2025 Jul;318:123133. doi: 10.1016/j.biomaterials.2025.123133. Epub 2025 Jan 24.
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@CeO) is designed. TBP@CeO 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@CeO nanozymes can effectively eliminate ROS and restore mitochondrial function, thereby decreasing the cytotoxicity on BRL 3A cells exposed to APAP/HO. The in vivo studies show that TBP@CeO 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.
开发具有增强活性以清除活性氧（ROS）的纳米药物已成为解决与ROS相关疾病（如药物性肝损伤）的一种有前景的策略。然而，设计不仅能清除ROS还能加速受损肝细胞修复的纳米酶仍然具有挑战性。在此，设计了一种具有线粒体靶向能力的双管齐下的黑磷/二氧化铈纳米酶（TBP@CeO）。TBP@CeO纳米酶表现出多酶活性，并显示出显著增强的ROS清除能力。它们可以通过清除过量的ROS和恢复线粒体复合物II的活性来促进能量依赖的肝细胞修复，从而有效减轻对乙酰氨基酚（APAP）诱导的肝损伤。体外实验表明，TBP@CeO纳米酶可以有效消除ROS并恢复线粒体功能，从而降低对暴露于APAP/HO的BRL 3A细胞的细胞毒性。体内研究表明，TBP@CeO纳米酶可以改善肝脏中的复合物II活性和线粒体功能，减少ROS并确保足够的三磷酸腺苷（ATP）产生，这有助于保护肝组织免受氧化损伤。本研究为纳米酶治疗ROS相关疾病引入了一种创新的设计策略。
