Hippo pathway-manipulating neutrophil-mimic hybrid nanoparticles for cardiac ischemic injury via modulation of local immunity and cardiac regeneration
The promise of regeneration therapy for restoration of damaged myocardium after cardiac ischemic injury relies on targeted delivery of proliferative molecules into cardiomyocytes whose healing benefits are still limited owing to severe immune microenvironment due to local high concentration of proin...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383523003271 |
| _version_ | 1797454612416954368 |
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| author | Qiaozi Wang Yanan Song Jinfeng Gao Qiyu Li Jing Chen Yifang Xie Zhengmin Wang Haipeng Tan Hongbo Yang Ning Zhang Juying Qian Zhiqing Pang Zheyong Huang Junbo Ge |
| author_facet | Qiaozi Wang Yanan Song Jinfeng Gao Qiyu Li Jing Chen Yifang Xie Zhengmin Wang Haipeng Tan Hongbo Yang Ning Zhang Juying Qian Zhiqing Pang Zheyong Huang Junbo Ge |
| author_sort | Qiaozi Wang |
| collection | DOAJ |
| description | The promise of regeneration therapy for restoration of damaged myocardium after cardiac ischemic injury relies on targeted delivery of proliferative molecules into cardiomyocytes whose healing benefits are still limited owing to severe immune microenvironment due to local high concentration of proinflammatory cytokines. Optimal therapeutic strategies are therefore in urgent need to both modulate local immunity and deliver proliferative molecules. Here, we addressed this unmet need by developing neutrophil-mimic nanoparticles NM@miR, fabricated by coating hybrid neutrophil membranes with artificial lipids onto mesoporous silica nanoparticles (MSNs) loaded with microRNA-10b. The hybrid membrane could endow nanoparticles with strong capacity to migrate into inflammatory sites and neutralize proinflammatory cytokines and increase the delivery efficiency of microRNA-10b into adult mammalian cardiomyocytes (CMs) by fusing with cell membranes and leading to the release of MSNs-miR into cytosol. Upon NM@miR administration, this nanoparticle could home to the injured myocardium, restore the local immunity, and efficiently deliver microRNA-10b to cardiomyocytes, which could reduce the activation of Hippo-YAP pathway mediated by excessive cytokines and exert the best proliferative effect of miR-10b. This combination therapy could finally improve cardiac function and mitigate ventricular remodeling. Consequently, this work offers a combination strategy of immunity modulation and proliferative molecule delivery to boost cardiac regeneration after injury. |
| first_indexed | 2024-03-09T15:40:36Z |
| format | Article |
| id | doaj.art-2a433261bee64e08a89b1acf3fd9ee6a |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-03-09T15:40:36Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-2a433261bee64e08a89b1acf3fd9ee6a2023-11-25T04:47:45ZengElsevierActa Pharmaceutica Sinica B2211-38352023-12-01131249995015Hippo pathway-manipulating neutrophil-mimic hybrid nanoparticles for cardiac ischemic injury via modulation of local immunity and cardiac regenerationQiaozi Wang0Yanan Song1Jinfeng Gao2Qiyu Li3Jing Chen4Yifang Xie5Zhengmin Wang6Haipeng Tan7Hongbo Yang8Ning Zhang9Juying Qian10Zhiqing Pang11Zheyong Huang12Junbo Ge13Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China; National Clinical Research Center for Interventional Medicine, Shanghai 200032, ChinaDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China; National Clinical Research Center for Interventional Medicine, Shanghai 200032, ChinaDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China; National Clinical Research Center for Interventional Medicine, Shanghai 200032, ChinaDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China; National Clinical Research Center for Interventional Medicine, Shanghai 200032, ChinaDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China; National Clinical Research Center for Interventional Medicine, Shanghai 200032, ChinaInstitute of Biomedical Sciences, Fudan University, Shanghai 200032, ChinaDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China; National Clinical Research Center for Interventional Medicine, Shanghai 200032, ChinaDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China; National Clinical Research Center for Interventional Medicine, Shanghai 200032, ChinaDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China; National Clinical Research Center for Interventional Medicine, Shanghai 200032, ChinaDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China; National Clinical Research Center for Interventional Medicine, Shanghai 200032, ChinaDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China; National Clinical Research Center for Interventional Medicine, Shanghai 200032, ChinaSchool of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai 201203, China; Corresponding authors.Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China; National Clinical Research Center for Interventional Medicine, Shanghai 200032, China; Corresponding authors.Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China; Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China; National Clinical Research Center for Interventional Medicine, Shanghai 200032, China; Corresponding authors.The promise of regeneration therapy for restoration of damaged myocardium after cardiac ischemic injury relies on targeted delivery of proliferative molecules into cardiomyocytes whose healing benefits are still limited owing to severe immune microenvironment due to local high concentration of proinflammatory cytokines. Optimal therapeutic strategies are therefore in urgent need to both modulate local immunity and deliver proliferative molecules. Here, we addressed this unmet need by developing neutrophil-mimic nanoparticles NM@miR, fabricated by coating hybrid neutrophil membranes with artificial lipids onto mesoporous silica nanoparticles (MSNs) loaded with microRNA-10b. The hybrid membrane could endow nanoparticles with strong capacity to migrate into inflammatory sites and neutralize proinflammatory cytokines and increase the delivery efficiency of microRNA-10b into adult mammalian cardiomyocytes (CMs) by fusing with cell membranes and leading to the release of MSNs-miR into cytosol. Upon NM@miR administration, this nanoparticle could home to the injured myocardium, restore the local immunity, and efficiently deliver microRNA-10b to cardiomyocytes, which could reduce the activation of Hippo-YAP pathway mediated by excessive cytokines and exert the best proliferative effect of miR-10b. This combination therapy could finally improve cardiac function and mitigate ventricular remodeling. Consequently, this work offers a combination strategy of immunity modulation and proliferative molecule delivery to boost cardiac regeneration after injury.http://www.sciencedirect.com/science/article/pii/S2211383523003271Myocardial infarctionCardiac regenerationBiomimetic nanoparticlesNeutrophilsImmunity restorationMicroRNA |
| spellingShingle | Qiaozi Wang Yanan Song Jinfeng Gao Qiyu Li Jing Chen Yifang Xie Zhengmin Wang Haipeng Tan Hongbo Yang Ning Zhang Juying Qian Zhiqing Pang Zheyong Huang Junbo Ge Hippo pathway-manipulating neutrophil-mimic hybrid nanoparticles for cardiac ischemic injury via modulation of local immunity and cardiac regeneration Acta Pharmaceutica Sinica B Myocardial infarction Cardiac regeneration Biomimetic nanoparticles Neutrophils Immunity restoration MicroRNA |
| title | Hippo pathway-manipulating neutrophil-mimic hybrid nanoparticles for cardiac ischemic injury via modulation of local immunity and cardiac regeneration |
| title_full | Hippo pathway-manipulating neutrophil-mimic hybrid nanoparticles for cardiac ischemic injury via modulation of local immunity and cardiac regeneration |
| title_fullStr | Hippo pathway-manipulating neutrophil-mimic hybrid nanoparticles for cardiac ischemic injury via modulation of local immunity and cardiac regeneration |
| title_full_unstemmed | Hippo pathway-manipulating neutrophil-mimic hybrid nanoparticles for cardiac ischemic injury via modulation of local immunity and cardiac regeneration |
| title_short | Hippo pathway-manipulating neutrophil-mimic hybrid nanoparticles for cardiac ischemic injury via modulation of local immunity and cardiac regeneration |
| title_sort | hippo pathway manipulating neutrophil mimic hybrid nanoparticles for cardiac ischemic injury via modulation of local immunity and cardiac regeneration |
| topic | Myocardial infarction Cardiac regeneration Biomimetic nanoparticles Neutrophils Immunity restoration MicroRNA |
| url | http://www.sciencedirect.com/science/article/pii/S2211383523003271 |
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