Neutrophil membrane fusogenic nanoliposomal leonurine for targeted ischemic stroke therapy via remodeling cerebral niche and restoring blood-brain barrier integrity
Ischemic stroke (IS) constitutes the leading cause of global morbidity and mortality. Neuroprotectants are essential to ameliorate the clinical prognosis, but their therapeutic outcomes are tremendously compromised by insufficient delivery to the ischemic lesion and intricate pathogenesis associated...
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| Language: | English |
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Elsevier
2023-06-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006423001345 |
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| author | Zhuang Tang Shiyu Meng Zhiling Song Xiaoxue Yang Xinzhi Li Hui Guo Meirong Du Jun Chen Yi Zhun Zhu Xiaolin Wang |
| author_facet | Zhuang Tang Shiyu Meng Zhiling Song Xiaoxue Yang Xinzhi Li Hui Guo Meirong Du Jun Chen Yi Zhun Zhu Xiaolin Wang |
| author_sort | Zhuang Tang |
| collection | DOAJ |
| description | Ischemic stroke (IS) constitutes the leading cause of global morbidity and mortality. Neuroprotectants are essential to ameliorate the clinical prognosis, but their therapeutic outcomes are tremendously compromised by insufficient delivery to the ischemic lesion and intricate pathogenesis associated with neuronal damage, oxidative stress, inflammation responses, blood-brain barrier (BBB) dysfunction, etc. Herein, a biomimetic nanosystem (Leo@NM-Lipo) composed of neutrophil membrane-fused nanoliposomal leonurine (Leo) is constructed, which can not only efficiently penetrate and repair the disrupted BBB but also robustly remodel the harsh cerebral microenvironment to reverse ischemia-reperfusion (I/R) injury. More specifically, the neutrophil membrane inherits the BBB penetrating, infarct core targeting, inflammation neutralization, and immune evasion properties of neutrophils, while Leo, a naturally occurring neuroprotectant, exerts pleiotropic effects to attenuate brain damage. Remarkably, comprehensive investigations disclose the critical factors influencing the targetability and therapeutic performances of biomimetic nanosystems. Leo@NM-Lipo with a low membrane protein-to-lipid ratio of 1:10 efficiently targets the ischemic lesion and rescues the injured brain by alleviating neuronal apoptosis, oxidative stress, neuroinflammation, and restoring BBB integrity in transient middle cerebral artery occlusion (tMCAO) rats. Taken together, our study provides a neutrophil-mimetic nanoplatform for targeted IS therapy and sheds light on the rational design of biomimetic nanosystems favoring wide medical applications. |
| first_indexed | 2024-03-13T03:32:23Z |
| format | Article |
| id | doaj.art-5f887eb63e094939ad473c855c28679c |
| institution | Directory Open Access Journal |
| issn | 2590-0064 |
| language | English |
| last_indexed | 2024-03-13T03:32:23Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj.art-5f887eb63e094939ad473c855c28679c2023-06-24T05:18:45ZengElsevierMaterials Today Bio2590-00642023-06-0120100674Neutrophil membrane fusogenic nanoliposomal leonurine for targeted ischemic stroke therapy via remodeling cerebral niche and restoring blood-brain barrier integrityZhuang Tang0Shiyu Meng1Zhiling Song2Xiaoxue Yang3Xinzhi Li4Hui Guo5Meirong Du6Jun Chen7Yi Zhun Zhu8Xiaolin Wang9School of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao 999078, ChinaSchool of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao 999078, ChinaSchool of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao 999078, ChinaSchool of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao 999078, ChinaSchool of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao 999078, ChinaSchool of Chemical Engineering and Technology, Sun Yat-sen University, Zhuhai 519082, ChinaSchool of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao 999078, China; NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200032, ChinaSchool of Pharmacy, Fudan University, Shanghai 201203, ChinaSchool of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao 999078, China; Corresponding author.School of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao 999078, China; Corresponding author.Ischemic stroke (IS) constitutes the leading cause of global morbidity and mortality. Neuroprotectants are essential to ameliorate the clinical prognosis, but their therapeutic outcomes are tremendously compromised by insufficient delivery to the ischemic lesion and intricate pathogenesis associated with neuronal damage, oxidative stress, inflammation responses, blood-brain barrier (BBB) dysfunction, etc. Herein, a biomimetic nanosystem (Leo@NM-Lipo) composed of neutrophil membrane-fused nanoliposomal leonurine (Leo) is constructed, which can not only efficiently penetrate and repair the disrupted BBB but also robustly remodel the harsh cerebral microenvironment to reverse ischemia-reperfusion (I/R) injury. More specifically, the neutrophil membrane inherits the BBB penetrating, infarct core targeting, inflammation neutralization, and immune evasion properties of neutrophils, while Leo, a naturally occurring neuroprotectant, exerts pleiotropic effects to attenuate brain damage. Remarkably, comprehensive investigations disclose the critical factors influencing the targetability and therapeutic performances of biomimetic nanosystems. Leo@NM-Lipo with a low membrane protein-to-lipid ratio of 1:10 efficiently targets the ischemic lesion and rescues the injured brain by alleviating neuronal apoptosis, oxidative stress, neuroinflammation, and restoring BBB integrity in transient middle cerebral artery occlusion (tMCAO) rats. Taken together, our study provides a neutrophil-mimetic nanoplatform for targeted IS therapy and sheds light on the rational design of biomimetic nanosystems favoring wide medical applications.http://www.sciencedirect.com/science/article/pii/S2590006423001345Neutrophil-mimeticLeonurineIschemic strokeTargeted therapyBlood-brain barrier |
| spellingShingle | Zhuang Tang Shiyu Meng Zhiling Song Xiaoxue Yang Xinzhi Li Hui Guo Meirong Du Jun Chen Yi Zhun Zhu Xiaolin Wang Neutrophil membrane fusogenic nanoliposomal leonurine for targeted ischemic stroke therapy via remodeling cerebral niche and restoring blood-brain barrier integrity Materials Today Bio Neutrophil-mimetic Leonurine Ischemic stroke Targeted therapy Blood-brain barrier |
| title | Neutrophil membrane fusogenic nanoliposomal leonurine for targeted ischemic stroke therapy via remodeling cerebral niche and restoring blood-brain barrier integrity |
| title_full | Neutrophil membrane fusogenic nanoliposomal leonurine for targeted ischemic stroke therapy via remodeling cerebral niche and restoring blood-brain barrier integrity |
| title_fullStr | Neutrophil membrane fusogenic nanoliposomal leonurine for targeted ischemic stroke therapy via remodeling cerebral niche and restoring blood-brain barrier integrity |
| title_full_unstemmed | Neutrophil membrane fusogenic nanoliposomal leonurine for targeted ischemic stroke therapy via remodeling cerebral niche and restoring blood-brain barrier integrity |
| title_short | Neutrophil membrane fusogenic nanoliposomal leonurine for targeted ischemic stroke therapy via remodeling cerebral niche and restoring blood-brain barrier integrity |
| title_sort | neutrophil membrane fusogenic nanoliposomal leonurine for targeted ischemic stroke therapy via remodeling cerebral niche and restoring blood brain barrier integrity |
| topic | Neutrophil-mimetic Leonurine Ischemic stroke Targeted therapy Blood-brain barrier |
| url | http://www.sciencedirect.com/science/article/pii/S2590006423001345 |
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