Department of Pharmaceutics, College of Pharmacy, Third Military Medical University (Army Medical University), Chongqing 400038, China.
Biomater Sci. 2020 Dec 15;8(24):7117-7131. doi: 10.1039/d0bm01660h.
Drug-induced tissue injury has become a growing public health problem. Gastrointestinal injury and liver dysfunction are the most common side effects related to drug therapies, resulting in high morbidity and mortality in recent years. The overproduction of reactive oxygen species (ROS) is critically involved in the pathogenesis of drug-induced tissue injury. Consequently, antioxidant therapy represents a very promising strategy for the treatment of drug-induced tissue injury. Herein, a multifunctional antioxidant nanotherapy (TON) is engineered from a cyclodextrin-derived ROS-responsive material and a radical scavenger tempol, and is capable of eliminating a broad spectrum of ROS. After oral administration, TON can passively accumulate in the inflamed gastrointestinal tissues in mice with indomethacin-induced gastrointestinal injury. Correspondingly, TON shows superior efficacy in two representative murine models of indomethacin-induced gastrointestinal injury and acetaminophen-induced hepatic injury via attenuating oxidative stress and mitigating inflammatory responses. Additionally, preliminary in vitro and in vivo experiments demonstrate the good safety profile of TON. Consequently, the ROS-responsive antioxidant nanotherapy TON is promising for the treatment of drug-induced tissue and organ injury.
药物诱导的组织损伤已成为一个日益严重的公共卫生问题。胃肠道损伤和肝功能障碍是与药物治疗最常见的副作用，导致近年来发病率和死亡率高。活性氧（ROS）的过度产生在药物诱导的组织损伤发病机制中起关键作用。因此，抗氧化治疗代表了治疗药物诱导的组织损伤的一种很有前途的策略。在此，设计了一种多功能抗氧化纳米治疗（TON），它由环糊精衍生的 ROS 响应材料和自由基清除剂 Tempo 组成，能够消除广泛的 ROS。口服后，TON 可以在吲哚美辛诱导的胃肠道损伤的小鼠的炎症胃肠道组织中被动积累。相应地，TON 通过减轻氧化应激和减轻炎症反应，在两种代表性的吲哚美辛诱导的胃肠道损伤和对乙酰氨基酚诱导的肝损伤的小鼠模型中显示出优越的疗效。此外，初步的体外和体内实验证明了 TON 的良好安全性。因此，ROS 响应性抗氧化纳米治疗 TON 有望用于治疗药物引起的组织和器官损伤。
