Biomimetic astrocyte cell membrane-fused nanovesicles for protecting neurovascular units in hypoxic ischemic encephalopathy
Abstract Hypoxic ischemic encephalopathy (HIE) refers to neonatal hypoxic brain injury caused by severe asphyxia during the perinatal period. With a high incidence rate and poor prognosis, HIE accounts for 2.4% of the global disease burden, imposing a heavy burden on families and society. Current cl...
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BMC
2024-12-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-024-03053-8 |
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| author | Zihao Liu Qian Xia Chanyue Wang Jiacan Xu Kangqian Tian Zhihai Wang Longji Li Yuchen Li Hao Shang Qian Liu Tao Xin |
| author_facet | Zihao Liu Qian Xia Chanyue Wang Jiacan Xu Kangqian Tian Zhihai Wang Longji Li Yuchen Li Hao Shang Qian Liu Tao Xin |
| author_sort | Zihao Liu |
| collection | DOAJ |
| description | Abstract Hypoxic ischemic encephalopathy (HIE) refers to neonatal hypoxic brain injury caused by severe asphyxia during the perinatal period. With a high incidence rate and poor prognosis, HIE accounts for 2.4% of the global disease burden, imposing a heavy burden on families and society. Current clinical treatment for HIE primarily focuses on symptomatic management and supportive care. Therefore, the developments of effective treatment strategies and new drug formulations are critical for improving the prognosis of HIE patients. In order to protect the compromised neurovascular units after HIE, we prepared membrane-fused nanovesicles for delivering rapamycin and si EDN1 (TRCAM@RAPA@si EDN1). Due to the homotypic targeting feature of membrane-fused nanovesicles, we employed astrocyte membranes as synthetic materials to improve the targeting of astrocytes in brain while reducing the clearance of nanovesicles by circulatory system. Additionally, the surface of cell membrane was modified with CXCR3 receptors, enhancing the homing of nanovesicles to infarcted lesions. Lipid vesicles were modified with TK and RVG29 transmembrane peptides, enabling responsive release of internal drugs and blood-brain barrier penetration. Internally loaded rapamycin could promote protective autophagy in astrocytes, improve cellular oxidative stress, while si EDN1 could reduce the expression level of endothelin gene, thereby reducing secondary damage to neurovascular units. Graphical Abstract |
| format | Article |
| id | doaj-art-75eb5de8d8f14940b21925f0f4f804a0 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-75eb5de8d8f14940b21925f0f4f804a02024-12-22T12:45:28ZengBMCJournal of Nanobiotechnology1477-31552024-12-0122111810.1186/s12951-024-03053-8Biomimetic astrocyte cell membrane-fused nanovesicles for protecting neurovascular units in hypoxic ischemic encephalopathyZihao Liu0Qian Xia1Chanyue Wang2Jiacan Xu3Kangqian Tian4Zhihai Wang5Longji Li6Yuchen Li7Hao Shang8Qian Liu9Tao Xin10Department of Neurosurgery, Shandong Provincial Hospital, Shandong First Medical UniversityDepartment of Endocrinology, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityDepartment of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityDepartment of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Shandong First Medical UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Shandong First Medical UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Shandong First Medical UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Shandong First Medical UniversityDepartment of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Shandong First Medical UniversityAbstract Hypoxic ischemic encephalopathy (HIE) refers to neonatal hypoxic brain injury caused by severe asphyxia during the perinatal period. With a high incidence rate and poor prognosis, HIE accounts for 2.4% of the global disease burden, imposing a heavy burden on families and society. Current clinical treatment for HIE primarily focuses on symptomatic management and supportive care. Therefore, the developments of effective treatment strategies and new drug formulations are critical for improving the prognosis of HIE patients. In order to protect the compromised neurovascular units after HIE, we prepared membrane-fused nanovesicles for delivering rapamycin and si EDN1 (TRCAM@RAPA@si EDN1). Due to the homotypic targeting feature of membrane-fused nanovesicles, we employed astrocyte membranes as synthetic materials to improve the targeting of astrocytes in brain while reducing the clearance of nanovesicles by circulatory system. Additionally, the surface of cell membrane was modified with CXCR3 receptors, enhancing the homing of nanovesicles to infarcted lesions. Lipid vesicles were modified with TK and RVG29 transmembrane peptides, enabling responsive release of internal drugs and blood-brain barrier penetration. Internally loaded rapamycin could promote protective autophagy in astrocytes, improve cellular oxidative stress, while si EDN1 could reduce the expression level of endothelin gene, thereby reducing secondary damage to neurovascular units. Graphical Abstracthttps://doi.org/10.1186/s12951-024-03053-8Hypoxic ischemic encephalopathyCell membrane-fused nanovesicleNeurovascular unitsAstrocyteAutophagy |
| spellingShingle | Zihao Liu Qian Xia Chanyue Wang Jiacan Xu Kangqian Tian Zhihai Wang Longji Li Yuchen Li Hao Shang Qian Liu Tao Xin Biomimetic astrocyte cell membrane-fused nanovesicles for protecting neurovascular units in hypoxic ischemic encephalopathy Journal of Nanobiotechnology Hypoxic ischemic encephalopathy Cell membrane-fused nanovesicle Neurovascular units Astrocyte Autophagy |
| title | Biomimetic astrocyte cell membrane-fused nanovesicles for protecting neurovascular units in hypoxic ischemic encephalopathy |
| title_full | Biomimetic astrocyte cell membrane-fused nanovesicles for protecting neurovascular units in hypoxic ischemic encephalopathy |
| title_fullStr | Biomimetic astrocyte cell membrane-fused nanovesicles for protecting neurovascular units in hypoxic ischemic encephalopathy |
| title_full_unstemmed | Biomimetic astrocyte cell membrane-fused nanovesicles for protecting neurovascular units in hypoxic ischemic encephalopathy |
| title_short | Biomimetic astrocyte cell membrane-fused nanovesicles for protecting neurovascular units in hypoxic ischemic encephalopathy |
| title_sort | biomimetic astrocyte cell membrane fused nanovesicles for protecting neurovascular units in hypoxic ischemic encephalopathy |
| topic | Hypoxic ischemic encephalopathy Cell membrane-fused nanovesicle Neurovascular units Astrocyte Autophagy |
| url | https://doi.org/10.1186/s12951-024-03053-8 |
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