Chen Chongqing, Wu Haitao, Li Qianhui, Liu Menghua, Yin Fan, Wu Miaomiao, Wei Xiaoli, Wang Hua, Zha Zhengbao, Wang Fei
School of Pharmacy, Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei 230032, China.
Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Biomater Sci. 2023 Mar 28;11(7):2348-2358. doi: 10.1039/d2bm01968j.
As one of the leading cases of acute liver failure triggered by excessive Acetaminophen (APAP), breakdown of the antioxidant system, inflammatory response, and inescapable apoptosis following overaccumulation of reactive oxygen species (ROS) play crucial roles in the mechanisms of APAP-induced liver injury (AILI). Therefore, cutting off ROS overproduction at the source is considered promising. Here, manganese Prussian blue nanozymes (MPBZs) with superior antioxidant enzyme-like activity are prepared as an effective strategy for hepatocyte protection, in which MPBZs accumulated in the liver show anti-oxidation properties by scavenging superfluous ROS. Importantly, in addition to alleviating oxidative stress, bioactive MPBZs with abundant variable valence states as a natural antioxidant enzymes mediated the responses of multi-biological signaling pathways and , including Nrf2-Keap1, NF-κB, and mitochondrial-induced apoptosis signaling pathways, enhancing tolerance for imminent AILI. Taking nanomedicine, hepatology, and catalytic chemistry into consideration, the revealed superior performance of AILI prevention suggests that MPBZ-based nano-detoxification therapy may offer an effective alternative against AILI.
作为对乙酰氨基酚（APAP）过量引发急性肝衰竭的主要病例之一，抗氧化系统的崩溃、炎症反应以及活性氧（ROS）过度积累后不可避免的细胞凋亡在APAP诱导的肝损伤（AILI）机制中起关键作用。因此，从源头上切断ROS的过度产生被认为是有前景的。在此，制备具有优异类抗氧化酶活性的锰普鲁士蓝纳米酶（MPBZs）作为肝细胞保护的有效策略，其中在肝脏中积累的MPBZs通过清除多余的ROS表现出抗氧化特性。重要的是，除了减轻氧化应激外，具有丰富可变价态的生物活性MPBZs作为天然抗氧化酶介导了包括Nrf2-Keap1、NF-κB和线粒体诱导的凋亡信号通路在内的多生物信号通路的反应，增强了对即将发生的AILI的耐受性。考虑到纳米医学、肝病学和催化化学，所揭示的预防AILI的卓越性能表明基于MPBZ的纳米解毒疗法可能为对抗AILI提供一种有效的替代方法。
