Engineered inhaled nanocatalytic therapy for ischemic cerebrovascular disease by inducing autophagy of abnormal mitochondria
Abstract 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,...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-08-01
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| Series: | npj Regenerative Medicine |
| Online Access: | https://doi.org/10.1038/s41536-023-00315-1 |
| _version_ | 1827724164680646656 |
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| author | Deping Wang Bowen Li Shuchao Wang Yingjian Hao Hua Wang Wei Sun Jimin Cao Xin Zhou Bin Zheng |
| author_facet | Deping Wang Bowen Li Shuchao Wang Yingjian Hao Hua Wang Wei Sun Jimin Cao Xin Zhou Bin Zheng |
| author_sort | Deping Wang |
| collection | DOAJ |
| description | Abstract 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/Co3O4, to treat ischemic cerebrovascular disease. Mn/Co3O4 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/Co3O4 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/Co3O4 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. |
| first_indexed | 2024-03-10T22:10:51Z |
| format | Article |
| id | doaj.art-f958ce1186764c08a87b5a663dd90252 |
| institution | Directory Open Access Journal |
| issn | 2057-3995 |
| language | English |
| last_indexed | 2024-03-10T22:10:51Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Regenerative Medicine |
| spelling | doaj.art-f958ce1186764c08a87b5a663dd902522023-11-19T12:36:58ZengNature Portfolionpj Regenerative Medicine2057-39952023-08-018111410.1038/s41536-023-00315-1Engineered inhaled nanocatalytic therapy for ischemic cerebrovascular disease by inducing autophagy of abnormal mitochondriaDeping Wang0Bowen Li1Shuchao Wang2Yingjian Hao3Hua Wang4Wei Sun5Jimin Cao6Xin Zhou7Bin Zheng8Academy of Medical Engineering and Translational Medicine, Tianjin Key Laboratory of Brain Science and Neural Engineering, Xincheng Hospital of Tianjin University, Tianjin UniversityAcademy of Medical Engineering and Translational Medicine, Tianjin Key Laboratory of Brain Science and Neural Engineering, Xincheng Hospital of Tianjin University, Tianjin UniversityAcademy of Medical Engineering and Translational Medicine, Tianjin Key Laboratory of Brain Science and Neural Engineering, Xincheng Hospital of Tianjin University, Tianjin UniversityKey Laboratory of Cellular Physiology, Ministry of Education, and the Department of Physiology, Shanxi Medical UniversitySchool of Pharmaceutical Science and Technology, Tianjin UniversityAcademy of Medical Engineering and Translational Medicine, Tianjin Key Laboratory of Brain Science and Neural Engineering, Xincheng Hospital of Tianjin University, Tianjin UniversityKey Laboratory of Cellular Physiology, Ministry of Education, and the Department of Physiology, Shanxi Medical UniversityKey Laboratory of Cellular Physiology, Ministry of Education, and the Department of Physiology, Shanxi Medical UniversityAcademy of Medical Engineering and Translational Medicine, Tianjin Key Laboratory of Brain Science and Neural Engineering, Xincheng Hospital of Tianjin University, Tianjin UniversityAbstract 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/Co3O4, to treat ischemic cerebrovascular disease. Mn/Co3O4 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/Co3O4 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/Co3O4 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.https://doi.org/10.1038/s41536-023-00315-1 |
| spellingShingle | Deping Wang Bowen Li Shuchao Wang Yingjian Hao Hua Wang Wei Sun Jimin Cao Xin Zhou Bin Zheng Engineered inhaled nanocatalytic therapy for ischemic cerebrovascular disease by inducing autophagy of abnormal mitochondria npj Regenerative Medicine |
| title | Engineered inhaled nanocatalytic therapy for ischemic cerebrovascular disease by inducing autophagy of abnormal mitochondria |
| title_full | Engineered inhaled nanocatalytic therapy for ischemic cerebrovascular disease by inducing autophagy of abnormal mitochondria |
| title_fullStr | Engineered inhaled nanocatalytic therapy for ischemic cerebrovascular disease by inducing autophagy of abnormal mitochondria |
| title_full_unstemmed | Engineered inhaled nanocatalytic therapy for ischemic cerebrovascular disease by inducing autophagy of abnormal mitochondria |
| title_short | Engineered inhaled nanocatalytic therapy for ischemic cerebrovascular disease by inducing autophagy of abnormal mitochondria |
| title_sort | engineered inhaled nanocatalytic therapy for ischemic cerebrovascular disease by inducing autophagy of abnormal mitochondria |
| url | https://doi.org/10.1038/s41536-023-00315-1 |
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