Anti-CHAC1 exosomes for nose-to-brain delivery of miR-760-3p in cerebral ischemia/reperfusion injury mice inhibiting neuron ferroptosis
Abstract Ferroptosis plays a critical role in ischemic stroke, and anti-ferroptosis strategies were regarded as potentially effective measures. Based on ferroptosis-related mechanisms, this study aims to design and prepare anti-ferroptosis exosomes from adipose-derived mesenchymal stem cells (ADSC-E...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-03-01
|
| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-023-01862-x |
| _version_ | 1827974378627792896 |
|---|---|
| author | Yong Wang Huicong Niu Luyu Li Jing Han Zhuohang Liu Min Chu Xianyi Sha Jing Zhao |
| author_facet | Yong Wang Huicong Niu Luyu Li Jing Han Zhuohang Liu Min Chu Xianyi Sha Jing Zhao |
| author_sort | Yong Wang |
| collection | DOAJ |
| description | Abstract Ferroptosis plays a critical role in ischemic stroke, and anti-ferroptosis strategies were regarded as potentially effective measures. Based on ferroptosis-related mechanisms, this study aims to design and prepare anti-ferroptosis exosomes from adipose-derived mesenchymal stem cells (ADSC-Exo) for treating ischemic brain injury via intranasal (IN) administration. According to the bioinformatic analysis, CHAC1 was a key gene in the progress of ferroptosis in ischemic stroke. miR-760-3p can inhibit the expression of CHAC1 and may be abundant in ADSC-Exo. Therefore, ADSC-Exo were successfully isolated and the immunofluorescence showed that they can be efficiently delivered to the brain via IN administration. Additionally, IN administration of ADSC-Exo can effectively improve the neurobehavior function of mice after I/R, and improve the ferroptosis-related outcomes. As the immunofluorescence showed the co-localization of NeuN with CHAC1 obviously, we further evaluated the systematic effect of ADSC-Exo in an oxygen–glucose deprivation (OGD) mouse neuroblastoma cell line N2a model. The results showed that miR-760-3p in ADSC‐Exo contributed to their function in inhibiting ferroptosis by targeting CHAC1 in neurons. Collectively, the present study successfully designed and prepared anti-CHAC1 ADSC-Exo and suggested a promising exosome-based strategy for anti-ferroptosis therapy in cerebral ischemia/reperfusion injury. Graphical abstract |
| first_indexed | 2024-04-09T19:53:27Z |
| format | Article |
| id | doaj.art-bd2c54daa487426d9039ca63b41777a0 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-09T19:53:27Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-bd2c54daa487426d9039ca63b41777a02023-04-03T05:39:38ZengBMCJournal of Nanobiotechnology1477-31552023-03-0121111910.1186/s12951-023-01862-xAnti-CHAC1 exosomes for nose-to-brain delivery of miR-760-3p in cerebral ischemia/reperfusion injury mice inhibiting neuron ferroptosisYong Wang0Huicong Niu1Luyu Li2Jing Han3Zhuohang Liu4Min Chu5Xianyi Sha6Jing Zhao7Department of Neurology, Minhang Hospital, Fudan UniversityDepartment of Neurology, Minhang Hospital, Fudan UniversityDepartment of Dermatology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of MedicineState Key Laboratory of Medical Neurobiology, Department of Integrative Medicine and Neurobiology, Brain Science Collaborative Innovation Center, School of Basic Medical Sciences, Institutes of Brain Science, Fudan Institutes of Integrative Medicine, Fudan UniversityDepartment of Neurology, Minhang Hospital, Fudan UniversityDepartment of Neurology, Minhang Hospital, Fudan UniversityKey Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan UniversityDepartment of Neurology, Minhang Hospital, Fudan UniversityAbstract Ferroptosis plays a critical role in ischemic stroke, and anti-ferroptosis strategies were regarded as potentially effective measures. Based on ferroptosis-related mechanisms, this study aims to design and prepare anti-ferroptosis exosomes from adipose-derived mesenchymal stem cells (ADSC-Exo) for treating ischemic brain injury via intranasal (IN) administration. According to the bioinformatic analysis, CHAC1 was a key gene in the progress of ferroptosis in ischemic stroke. miR-760-3p can inhibit the expression of CHAC1 and may be abundant in ADSC-Exo. Therefore, ADSC-Exo were successfully isolated and the immunofluorescence showed that they can be efficiently delivered to the brain via IN administration. Additionally, IN administration of ADSC-Exo can effectively improve the neurobehavior function of mice after I/R, and improve the ferroptosis-related outcomes. As the immunofluorescence showed the co-localization of NeuN with CHAC1 obviously, we further evaluated the systematic effect of ADSC-Exo in an oxygen–glucose deprivation (OGD) mouse neuroblastoma cell line N2a model. The results showed that miR-760-3p in ADSC‐Exo contributed to their function in inhibiting ferroptosis by targeting CHAC1 in neurons. Collectively, the present study successfully designed and prepared anti-CHAC1 ADSC-Exo and suggested a promising exosome-based strategy for anti-ferroptosis therapy in cerebral ischemia/reperfusion injury. Graphical abstracthttps://doi.org/10.1186/s12951-023-01862-xCerebral ischemiaExosomesFerroptosisIntranasal administrationCHAC1 |
| spellingShingle | Yong Wang Huicong Niu Luyu Li Jing Han Zhuohang Liu Min Chu Xianyi Sha Jing Zhao Anti-CHAC1 exosomes for nose-to-brain delivery of miR-760-3p in cerebral ischemia/reperfusion injury mice inhibiting neuron ferroptosis Journal of Nanobiotechnology Cerebral ischemia Exosomes Ferroptosis Intranasal administration CHAC1 |
| title | Anti-CHAC1 exosomes for nose-to-brain delivery of miR-760-3p in cerebral ischemia/reperfusion injury mice inhibiting neuron ferroptosis |
| title_full | Anti-CHAC1 exosomes for nose-to-brain delivery of miR-760-3p in cerebral ischemia/reperfusion injury mice inhibiting neuron ferroptosis |
| title_fullStr | Anti-CHAC1 exosomes for nose-to-brain delivery of miR-760-3p in cerebral ischemia/reperfusion injury mice inhibiting neuron ferroptosis |
| title_full_unstemmed | Anti-CHAC1 exosomes for nose-to-brain delivery of miR-760-3p in cerebral ischemia/reperfusion injury mice inhibiting neuron ferroptosis |
| title_short | Anti-CHAC1 exosomes for nose-to-brain delivery of miR-760-3p in cerebral ischemia/reperfusion injury mice inhibiting neuron ferroptosis |
| title_sort | anti chac1 exosomes for nose to brain delivery of mir 760 3p in cerebral ischemia reperfusion injury mice inhibiting neuron ferroptosis |
| topic | Cerebral ischemia Exosomes Ferroptosis Intranasal administration CHAC1 |
| url | https://doi.org/10.1186/s12951-023-01862-x |
| work_keys_str_mv | AT yongwang antichac1exosomesfornosetobraindeliveryofmir7603pincerebralischemiareperfusioninjurymiceinhibitingneuronferroptosis AT huicongniu antichac1exosomesfornosetobraindeliveryofmir7603pincerebralischemiareperfusioninjurymiceinhibitingneuronferroptosis AT luyuli antichac1exosomesfornosetobraindeliveryofmir7603pincerebralischemiareperfusioninjurymiceinhibitingneuronferroptosis AT jinghan antichac1exosomesfornosetobraindeliveryofmir7603pincerebralischemiareperfusioninjurymiceinhibitingneuronferroptosis AT zhuohangliu antichac1exosomesfornosetobraindeliveryofmir7603pincerebralischemiareperfusioninjurymiceinhibitingneuronferroptosis AT minchu antichac1exosomesfornosetobraindeliveryofmir7603pincerebralischemiareperfusioninjurymiceinhibitingneuronferroptosis AT xianyisha antichac1exosomesfornosetobraindeliveryofmir7603pincerebralischemiareperfusioninjurymiceinhibitingneuronferroptosis AT jingzhao antichac1exosomesfornosetobraindeliveryofmir7603pincerebralischemiareperfusioninjurymiceinhibitingneuronferroptosis |