Surface-modified engineered exosomes attenuated cerebral ischemia/reperfusion injury by targeting the delivery of quercetin towards impaired neurons
Abstract Background The incidence of ischemic stroke in the context of vascular disease is high, and the expression of growth-associated protein-43 (GAP43) increases when neurons are damaged or stimulated, especially in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). Experiment...
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| Format: | Article |
| Language: | English |
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BMC
2021-05-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-021-00879-4 |
| _version_ | 1811182862973534208 |
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| author | Lin Guo Zhixuan Huang Lijuan Huang Jia Liang Peng Wang Liang Zhao Yijie Shi |
| author_facet | Lin Guo Zhixuan Huang Lijuan Huang Jia Liang Peng Wang Liang Zhao Yijie Shi |
| author_sort | Lin Guo |
| collection | DOAJ |
| description | Abstract Background The incidence of ischemic stroke in the context of vascular disease is high, and the expression of growth-associated protein-43 (GAP43) increases when neurons are damaged or stimulated, especially in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). Experimental design We bioengineered neuron-targeting exosomes (Exo) conjugated to a monoclonal antibody against GAP43 (mAb GAP43) to promote the targeted delivery of quercetin (Que) to ischemic neurons with high GAP43 expression and investigated the ability of Exo to treat cerebral ischemia by scavenging reactive oxygen species (ROS). Results Our results suggested that Que loaded mAb GAP43 conjugated exosomes (Que/mAb GAP43-Exo) can specifically target damaged neurons through the interaction between Exo-delivered mAb GAP43 and GAP43 expressed in damaged neurons and improve survival of neurons by inhibiting ROS production through the activation of the Nrf2/HO-1 pathway. The brain infarct volume is smaller, and neurological recovery is more markedly improved following Que/mAb GAP43-Exo treatment than following free Que or Que-carrying exosome (Que-Exo) treatment in a rat induced by MCAO/R. Conclusions Que/mAb GAP43-Exo may serve a promising dual targeting and therapeutic drug delivery system for alleviating cerebral ischemia/reperfusion injury. |
| first_indexed | 2024-04-11T09:38:46Z |
| format | Article |
| id | doaj.art-5fa50a0043fe4374a289804eeb9b41f1 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-11T09:38:46Z |
| publishDate | 2021-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-5fa50a0043fe4374a289804eeb9b41f12022-12-22T04:31:27ZengBMCJournal of Nanobiotechnology1477-31552021-05-0119111510.1186/s12951-021-00879-4Surface-modified engineered exosomes attenuated cerebral ischemia/reperfusion injury by targeting the delivery of quercetin towards impaired neuronsLin Guo0Zhixuan Huang1Lijuan Huang2Jia Liang3Peng Wang4Liang Zhao5Yijie Shi6School of Pharmacy, Jinzhou Medical UniversitySchool of Pharmacy, Jinzhou Medical UniversitySchool of Pharmacy, Jinzhou Medical UniversityLife Science Institution, Jinzhou Medical UniversityKey Laboratory of Neurodegenerative Diseases of Liaoning Province, Jinzhou Medical UniversitySchool of Pharmacy, Jinzhou Medical UniversitySchool of Pharmacy, Jinzhou Medical UniversityAbstract Background The incidence of ischemic stroke in the context of vascular disease is high, and the expression of growth-associated protein-43 (GAP43) increases when neurons are damaged or stimulated, especially in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). Experimental design We bioengineered neuron-targeting exosomes (Exo) conjugated to a monoclonal antibody against GAP43 (mAb GAP43) to promote the targeted delivery of quercetin (Que) to ischemic neurons with high GAP43 expression and investigated the ability of Exo to treat cerebral ischemia by scavenging reactive oxygen species (ROS). Results Our results suggested that Que loaded mAb GAP43 conjugated exosomes (Que/mAb GAP43-Exo) can specifically target damaged neurons through the interaction between Exo-delivered mAb GAP43 and GAP43 expressed in damaged neurons and improve survival of neurons by inhibiting ROS production through the activation of the Nrf2/HO-1 pathway. The brain infarct volume is smaller, and neurological recovery is more markedly improved following Que/mAb GAP43-Exo treatment than following free Que or Que-carrying exosome (Que-Exo) treatment in a rat induced by MCAO/R. Conclusions Que/mAb GAP43-Exo may serve a promising dual targeting and therapeutic drug delivery system for alleviating cerebral ischemia/reperfusion injury.https://doi.org/10.1186/s12951-021-00879-4ROSIschemiaQuercetinExosomesGAP43 |
| spellingShingle | Lin Guo Zhixuan Huang Lijuan Huang Jia Liang Peng Wang Liang Zhao Yijie Shi Surface-modified engineered exosomes attenuated cerebral ischemia/reperfusion injury by targeting the delivery of quercetin towards impaired neurons Journal of Nanobiotechnology ROS Ischemia Quercetin Exosomes GAP43 |
| title | Surface-modified engineered exosomes attenuated cerebral ischemia/reperfusion injury by targeting the delivery of quercetin towards impaired neurons |
| title_full | Surface-modified engineered exosomes attenuated cerebral ischemia/reperfusion injury by targeting the delivery of quercetin towards impaired neurons |
| title_fullStr | Surface-modified engineered exosomes attenuated cerebral ischemia/reperfusion injury by targeting the delivery of quercetin towards impaired neurons |
| title_full_unstemmed | Surface-modified engineered exosomes attenuated cerebral ischemia/reperfusion injury by targeting the delivery of quercetin towards impaired neurons |
| title_short | Surface-modified engineered exosomes attenuated cerebral ischemia/reperfusion injury by targeting the delivery of quercetin towards impaired neurons |
| title_sort | surface modified engineered exosomes attenuated cerebral ischemia reperfusion injury by targeting the delivery of quercetin towards impaired neurons |
| topic | ROS Ischemia Quercetin Exosomes GAP43 |
| url | https://doi.org/10.1186/s12951-021-00879-4 |
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