Wang Deping, Li Bowen, Wang Shuchao, Hao Yingjian, Wang Hua, Sun Wei, Cao Jimin, Zhou Xin, Zheng Bin
Academy of Medical Engineering and Translational Medicine, Tianjin Key Laboratory of Brain Science and Neural Engineering, Xincheng Hospital of Tianjin University, Tianjin University, Tianjin, 300072, China.
Key Laboratory of Cellular Physiology, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan, 030001, China.
NPJ Regen Med. 2023 Aug 11;8(1):44. doi: 10.1038/s41536-023-00315-1.
Mitochondrial dysfunction and subsequent accumulation of reactive oxygen species (ROS) are key contributors to the pathology of ischemic cerebrovascular disease. Therefore, elimination of ROS and damaged mitochondria is crucial for the effective treatment of this disease. For this purpose, we designed an inhalation nanotherapeutic agent, P/D@Mn/CoO, to treat ischemic cerebrovascular disease. Mn/CoO effectively removed excess ROS from cells, reduced acute cellular oxidative stress, and protected neural cells from apoptosis. Furthermore, it depleted the H surrounding mitochondria and depolarized the mitochondrial membrane potential, inducing mitophagy and eliminating abnormal mitochondria, thereby avoiding the continuous overproduction of ROS by eliminating the source of ROS regeneration. On intranasal administration, Mn/CoO encapsulated by platelet membranes and 2,3-(dioxy propyl)-trimethylammonium chloride can bypass the blood-brain barrier, enter the brain through the trigeminal and olfactory pathways, and target inflammatory regions to remove ROS and damaged mitochondria from the lesion area. In rat models of stroke and vascular dementia, P/D@Mn/CoO effectively inhibited the symptoms of acute and chronic cerebral ischemia by scavenging ROS and damaged mitochondria in the affected area. Our findings indicate that the nanotherapeutic agent developed in this study can be used for the effective treatment of ischemic cerebrovascular disease.
线粒体功能障碍及随后活性氧（ROS）的积累是缺血性脑血管病病理过程的关键因素。因此，清除ROS和受损线粒体对于有效治疗该疾病至关重要。为此，我们设计了一种吸入式纳米治疗剂P/D@Mn/CoO来治疗缺血性脑血管病。Mn/CoO能有效清除细胞内过量的ROS，减轻急性细胞氧化应激，并保护神经细胞免于凋亡。此外，它消耗线粒体周围的H，使线粒体膜电位去极化，诱导线粒体自噬并消除异常线粒体，从而通过消除ROS再生来源避免ROS的持续过量产生。经鼻给药时，被血小板膜和2,3-（二氧丙基）-三甲基氯化铵包裹的Mn/CoO可绕过血脑屏障，通过三叉神经和嗅觉途径进入大脑，并靶向炎症区域以清除病变区域的ROS和受损线粒体。在中风和血管性痴呆大鼠模型中，P/D@Mn/CoO通过清除受影响区域的ROS和受损线粒体，有效抑制了急性和慢性脑缺血症状。我们的研究结果表明，本研究开发的纳米治疗剂可用于有效治疗缺血性脑血管病。
