Wang Fengqin, Jiang Yinfang, Wang Yang
School of Mechanical Engineering, Nantong Institute of Technology, Nantong, Jiangsu, China.
Front Chem. 2025 Jan 20;13:1545850. doi: 10.3389/fchem.2025.1545850. eCollection 2025.
Carbon monoxide (CO) based gas therapy has recently garnered significant attention due to its remarkable therapeutic effects for various major diseases. However, the primary challenge in gas therapy is the effective delivery of gas prodrug to targeted sites, as well as achieving precise spatial-temporal control over their release behavior. In this work, we provide a facile method to design ROS-responsive and mitochondrial targeting CO-delivery nanoplatform, based on the thiol-functionalized metal-organic framework (MOF), abbreviated as UiO-66-SH, incorporating the drug resveratrol (RES) for combined tumor therapy. After endocytosis by tumor cells and localization within the mitochondria, UiO@FeCO@RES was decomposed by ATP to release RES and generate CO gas via a Fenton-like reaction between hydroxyl radicals (·OH) and FeCO. RES acts as an ATPase inhibitor, disrupting the metabolism of the respiratory chain in tumor cell and thereby facilitating ATP-blocked metabolic therapy. experimental results demonstrate that the combination therapy, involving both RES drug and CO gas therapy, exhibits a synergistic effect against cancer cells. This synergistic strategy has endowed UiO@FeCO@RES as a promising material for biomedical applications.
基于一氧化碳（CO）的气体疗法最近因其对各种重大疾病具有显著治疗效果而备受关注。然而，气体疗法的主要挑战在于将气体前药有效递送至靶向部位，并对其释放行为实现精确的时空控制。在这项工作中，我们提供了一种简便的方法来设计具有活性氧（ROS）响应性和线粒体靶向性的CO递送纳米平台，该平台基于硫醇功能化金属有机框架（MOF），简称为UiO-66-SH，并负载药物白藜芦醇（RES）用于联合肿瘤治疗。肿瘤细胞内吞并定位于线粒体后，UiO@FeCO@RES被三磷酸腺苷（ATP）分解以释放RES，并通过羟基自由基（·OH）与FeCO之间的类芬顿反应生成CO气体。RES作为一种ATP酶抑制剂，破坏肿瘤细胞呼吸链的代谢，从而促进ATP阻断的代谢疗法。实验结果表明，RES药物和CO气体疗法的联合治疗对癌细胞具有协同作用。这种协同策略使UiO@FeCO@RES成为一种有前途的生物医学应用材料。
