Pro-efferocytosis biomimetic nanocomplexes for targeted atherosclerosis therapy through promoting macrophage re-polarization and inhibiting senescence
Atherosclerosis is chronic inflammatory disease tightly related with defective efferocytosis of apoptotic cells (ACs) in the plaques. The strategy of efferocytosis reactivation using Atorvastatin (AT) and Metformin (Met) has attracted increasing attention for atherosclerosis treatment. Although thes...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | Materials & Design |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0264127523007311 |
| _version_ | 1797647984731619328 |
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| author | Peidong You Anning Yang Yue Sun Hongwen Zhang Yaling Zeng Yinju Hao Jiantuan Xiong Shengchao Ma Huiping Zhang Bin Liu Yideng Jiang |
| author_facet | Peidong You Anning Yang Yue Sun Hongwen Zhang Yaling Zeng Yinju Hao Jiantuan Xiong Shengchao Ma Huiping Zhang Bin Liu Yideng Jiang |
| author_sort | Peidong You |
| collection | DOAJ |
| description | Atherosclerosis is chronic inflammatory disease tightly related with defective efferocytosis of apoptotic cells (ACs) in the plaques. The strategy of efferocytosis reactivation using Atorvastatin (AT) and Metformin (Met) has attracted increasing attention for atherosclerosis treatment. Although these drug-based therapies could stimulate the phagocytic clearance of ACs, the rapid drug clearance and poor bioavailability limited their efficacy. In this study, by co-loading AT and Met into poly(lactic-co-glycolic) acid nanoparticles (PLGA NPs), we developed a biomimetic nanocomplexes for targeted atherosclerosis treatment. Macrophages membrane-coated nanocomplexes efficiently avoided the clearance of NPs from immune system and achieved targeting ability to the atherosclerotic plaques. Moreover, modified hyaluronic acid (HA) delivered NPs into the dysfunctional efferocytic cells of plaques, and achieved the plaques-macrophages-targeted therapy. In vitro results indicated that the biomimetic nanocomplexes reactivated efferocytosis by facilitating macrophages polarization from M1 to M2 phenotype through enhancing ERK5/MerTK pathway and inhibiting cellular senescence through inhibiting p53-p16/pRB pathway. In vivo study indicated that this biomimetic nanocomplexes accumulated in the atherosclerotic plaques, resulting in reduction of necrotic core area and protection against plaque rupture by reactivating efferocytosis. These findings indicated that reactivation of efferocytosis by AT and Met co-delivered nanocomplexes provided a novel promising strategy for targeted atherosclerosis treatment. |
| first_indexed | 2024-03-11T15:24:36Z |
| format | Article |
| id | doaj.art-ce89bd9213074a629ec642efe054f0ce |
| institution | Directory Open Access Journal |
| issn | 0264-1275 |
| language | English |
| last_indexed | 2024-03-11T15:24:36Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials & Design |
| spelling | doaj.art-ce89bd9213074a629ec642efe054f0ce2023-10-28T05:06:25ZengElsevierMaterials & Design0264-12752023-10-01234112316Pro-efferocytosis biomimetic nanocomplexes for targeted atherosclerosis therapy through promoting macrophage re-polarization and inhibiting senescencePeidong You0Anning Yang1Yue Sun2Hongwen Zhang3Yaling Zeng4Yinju Hao5Jiantuan Xiong6Shengchao Ma7Huiping Zhang8Bin Liu9Yideng Jiang10Department of Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China; NHC Key Laboratory of Metabolic Cardiovascular Diseases Research (Ningxia Medical University), Yinchuan 750004, China; General Hospital of Ningxia Medical University, Yinchuan 750004, ChinaDepartment of Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China; NHC Key Laboratory of Metabolic Cardiovascular Diseases Research (Ningxia Medical University), Yinchuan 750004, China; General Hospital of Ningxia Medical University, Yinchuan 750004, ChinaNHC Key Laboratory of Metabolic Cardiovascular Diseases Research (Ningxia Medical University), Yinchuan 750004, China; General Hospital of Ningxia Medical University, Yinchuan 750004, China; School of Public Health and Management, Ningxia Medical University, Yinchuan 750004, ChinaDepartment of Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China; NHC Key Laboratory of Metabolic Cardiovascular Diseases Research (Ningxia Medical University), Yinchuan 750004, China; Ningxia Key Laboratory of Vascular Injury and Repair Research, Yinchuan 750004, ChinaDepartment of Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China; NHC Key Laboratory of Metabolic Cardiovascular Diseases Research (Ningxia Medical University), Yinchuan 750004, China; Ningxia Key Laboratory of Vascular Injury and Repair Research, Yinchuan 750004, ChinaNHC Key Laboratory of Metabolic Cardiovascular Diseases Research (Ningxia Medical University), Yinchuan 750004, China; General Hospital of Ningxia Medical University, Yinchuan 750004, ChinaNHC Key Laboratory of Metabolic Cardiovascular Diseases Research (Ningxia Medical University), Yinchuan 750004, China; Ningxia Key Laboratory of Vascular Injury and Repair Research, Yinchuan 750004, ChinaDepartment of Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China; NHC Key Laboratory of Metabolic Cardiovascular Diseases Research (Ningxia Medical University), Yinchuan 750004, China; Ningxia Key Laboratory of Vascular Injury and Repair Research, Yinchuan 750004, ChinaHunan Provincial Maternal and Child Health Care Hospital, Changsha 410000, China; NHC Key Laboratory of Metabolic Cardiovascular Diseases Research (Ningxia Medical University), Yinchuan 750004, China; General Hospital of Ningxia Medical University, Yinchuan 750004, China; Corresponding authors at: Hunan Provincial Maternal and Child Health Care Hospital, Changsha 410000, China (Huiping Zhang). Department of Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China (Bin Liu, Yideng Jiang).Department of Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China; College of Biology, Hunan University, Changsha 410082, China; Corresponding authors at: Hunan Provincial Maternal and Child Health Care Hospital, Changsha 410000, China (Huiping Zhang). Department of Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China (Bin Liu, Yideng Jiang).Department of Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China; NHC Key Laboratory of Metabolic Cardiovascular Diseases Research (Ningxia Medical University), Yinchuan 750004, China; Ningxia Key Laboratory of Vascular Injury and Repair Research, Yinchuan 750004, China; Corresponding authors at: Hunan Provincial Maternal and Child Health Care Hospital, Changsha 410000, China (Huiping Zhang). Department of Pathophysiology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China (Bin Liu, Yideng Jiang).Atherosclerosis is chronic inflammatory disease tightly related with defective efferocytosis of apoptotic cells (ACs) in the plaques. The strategy of efferocytosis reactivation using Atorvastatin (AT) and Metformin (Met) has attracted increasing attention for atherosclerosis treatment. Although these drug-based therapies could stimulate the phagocytic clearance of ACs, the rapid drug clearance and poor bioavailability limited their efficacy. In this study, by co-loading AT and Met into poly(lactic-co-glycolic) acid nanoparticles (PLGA NPs), we developed a biomimetic nanocomplexes for targeted atherosclerosis treatment. Macrophages membrane-coated nanocomplexes efficiently avoided the clearance of NPs from immune system and achieved targeting ability to the atherosclerotic plaques. Moreover, modified hyaluronic acid (HA) delivered NPs into the dysfunctional efferocytic cells of plaques, and achieved the plaques-macrophages-targeted therapy. In vitro results indicated that the biomimetic nanocomplexes reactivated efferocytosis by facilitating macrophages polarization from M1 to M2 phenotype through enhancing ERK5/MerTK pathway and inhibiting cellular senescence through inhibiting p53-p16/pRB pathway. In vivo study indicated that this biomimetic nanocomplexes accumulated in the atherosclerotic plaques, resulting in reduction of necrotic core area and protection against plaque rupture by reactivating efferocytosis. These findings indicated that reactivation of efferocytosis by AT and Met co-delivered nanocomplexes provided a novel promising strategy for targeted atherosclerosis treatment.http://www.sciencedirect.com/science/article/pii/S0264127523007311AtherosclerosisEfferocytosisMacrophage polarizationSenescenceAtorvastatinMetformin |
| spellingShingle | Peidong You Anning Yang Yue Sun Hongwen Zhang Yaling Zeng Yinju Hao Jiantuan Xiong Shengchao Ma Huiping Zhang Bin Liu Yideng Jiang Pro-efferocytosis biomimetic nanocomplexes for targeted atherosclerosis therapy through promoting macrophage re-polarization and inhibiting senescence Materials & Design Atherosclerosis Efferocytosis Macrophage polarization Senescence Atorvastatin Metformin |
| title | Pro-efferocytosis biomimetic nanocomplexes for targeted atherosclerosis therapy through promoting macrophage re-polarization and inhibiting senescence |
| title_full | Pro-efferocytosis biomimetic nanocomplexes for targeted atherosclerosis therapy through promoting macrophage re-polarization and inhibiting senescence |
| title_fullStr | Pro-efferocytosis biomimetic nanocomplexes for targeted atherosclerosis therapy through promoting macrophage re-polarization and inhibiting senescence |
| title_full_unstemmed | Pro-efferocytosis biomimetic nanocomplexes for targeted atherosclerosis therapy through promoting macrophage re-polarization and inhibiting senescence |
| title_short | Pro-efferocytosis biomimetic nanocomplexes for targeted atherosclerosis therapy through promoting macrophage re-polarization and inhibiting senescence |
| title_sort | pro efferocytosis biomimetic nanocomplexes for targeted atherosclerosis therapy through promoting macrophage re polarization and inhibiting senescence |
| topic | Atherosclerosis Efferocytosis Macrophage polarization Senescence Atorvastatin Metformin |
| url | http://www.sciencedirect.com/science/article/pii/S0264127523007311 |
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