Jihong Liu, Dongni Yin, Wen Zhang, Xin Wang, Tony D. James, Ping Li, Bo Tang
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引用次数: 0
Abstract
Hepatic ischemia–reperfusion injury (HIRI) is the main cause of postoperative liver dysfunction and liver failure. Traditional separation of HIRI diagnosis and therapy confers several disadvantages, including the inability to visualize the therapeutic and asynchronous action. However, developing a versatile material with integrated diagnosis and treatment for HIRI remains a great challenge. Given that hypochlorous acid (HOCl) plays a crucial oxidative role in HIRI, we developed a single-component multifunctional fluorescent theranostic platform (MB-Gly) with a “three-in-one” molecular design incorporating a near-infrared fluorophore methylene blue, glycine and a HOCl-response unit, which could not only provide real-time visualization of HIRI but also boost targeted drug delivery. Using MB-Gly, we were able to achieve real-time and dynamic monitoring of HOCl during HIRI in hepatocytes and mouse livers and reduce the liver damage in hepatocytes and mice. RNA sequencing illustrated the therapeutic role of MB-Gly associated with changes in gene expression related to apoptosis, oxidative stress, metabolism and inflammation. To the best of our knowledge, this is the first multifunctional fluorescent theranostic system for HIRI reported to date. Our smart “three-in-one” approach shines light on the etiology and pathogenesis of HIRI, providing profound insights into the development of potential therapeutic targets.
肝缺血再灌注损伤(HIRI)是导致术后肝功能障碍和肝衰竭的主要原因。传统的肝缺血再灌注损伤诊断和治疗分离有几个缺点,包括无法观察治疗效果和作用不同步。然而,开发一种能综合诊断和治疗 HIRI 的多功能材料仍然是一项巨大的挑战。鉴于次氯酸(HOCl)在 HIRI 中起着关键的氧化作用,我们开发了一种单组分多功能荧光治疗平台(MB-Gly),其 "三合一 "分子设计融合了近红外荧光团亚甲基蓝、甘氨酸和 HOCl 反应单元,不仅能提供 HIRI 的实时可视化,还能促进靶向给药。利用 MB-Gly,我们能够实现肝细胞和小鼠肝脏 HIRI 期间 HOCl 的实时动态监测,并减少肝细胞和小鼠肝脏的损伤。RNA 测序表明,MB-Gly 的治疗作用与细胞凋亡、氧化应激、新陈代谢和炎症相关基因表达的变化有关。据我们所知,这是迄今为止报道的首个针对 HIRI 的多功能荧光治疗系统。我们的 "三合一 "智能方法揭示了 HIRI 的病因和发病机制,为开发潜在的治疗靶点提供了深刻的见解。
期刊介绍:
Chemical Science is a journal that encompasses various disciplines within the chemical sciences. Its scope includes publishing ground-breaking research with significant implications for its respective field, as well as appealing to a wider audience in related areas. To be considered for publication, articles must showcase innovative and original advances in their field of study and be presented in a manner that is understandable to scientists from diverse backgrounds. However, the journal generally does not publish highly specialized research.