A dual-targeting bio-liposomes nanodrug repair endothelial cell dysfunction and restore macrophage cholesterol flow homeostasis to treat early atherosclerosis
Abstract Hyperhomocysteinemia (HHy) can lead to vascular endothelial cell dysfunction, progressive inflammation and lipid metabolism disorder, which finally result in the onset and development of atherosclerosis, a major contributor to cardiovascular diseases. Given the complexity of pathological pr...
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BMC
2025-05-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03436-5 |
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| author | Qi Zhang Shengchao Ma Xue Kang Yi Liu Fei Ma Feifei Yu Xiaolan Luo Guizhong Li Yinju Hao Huiping Zhang Bin Liu Yideng Jiang |
| author_facet | Qi Zhang Shengchao Ma Xue Kang Yi Liu Fei Ma Feifei Yu Xiaolan Luo Guizhong Li Yinju Hao Huiping Zhang Bin Liu Yideng Jiang |
| author_sort | Qi Zhang |
| collection | DOAJ |
| description | Abstract Hyperhomocysteinemia (HHy) can lead to vascular endothelial cell dysfunction, progressive inflammation and lipid metabolism disorder, which finally result in the onset and development of atherosclerosis, a major contributor to cardiovascular diseases. Given the complexity of pathological process, treatments based on a single target often showed limited therapeutic efficacy against AS. Thus, developing nanodrug for enhanced multi-targets therapy is promising. In this study, we constructed a dual-targeting nanodrug (HA-ML@ES NPs) co-loaded with Shikonin (SKN) and Evolocumab (Evol). In vitro results showed that HA-ML@ES NPs could simultaneously target dysfunctional endothelial cell and inflammatory macrophage through the interaction between HA and CD44. In vivo assay indicated that HA-ML@ES NPs with long circulation and plaque accumulation efficiently attenuate endothelial cell dysfunction by inhibiting glycolysis and restore cholesterol flow homeostasis in macrophage by reprogramming macrophage phenotype, which finally attenuated the development of atherosclerosis. Collectively, these results present a highly promising dual-cell therapeutic approach based on HA-ML@ES NPs for the management of early atherosclerosis. |
| format | Article |
| id | doaj-art-a24eed08ff26467cb7ea5fd28f7ed7ff |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-a24eed08ff26467cb7ea5fd28f7ed7ff2025-08-20T03:48:18ZengBMCJournal of Nanobiotechnology1477-31552025-05-0123112110.1186/s12951-025-03436-5A dual-targeting bio-liposomes nanodrug repair endothelial cell dysfunction and restore macrophage cholesterol flow homeostasis to treat early atherosclerosisQi Zhang0Shengchao Ma1Xue Kang2Yi Liu3Fei Ma4Feifei Yu5Xiaolan Luo6Guizhong Li7Yinju Hao8Huiping Zhang9Bin Liu10Yideng Jiang11School of Inspection, Ningxia Medical UniversitySchool of Inspection, Ningxia Medical UniversityDepartment of Clinical Medicine, Ningxia Medical UniversityNHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical UniversityNHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical UniversityNHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical UniversitySchool of Inspection, Ningxia Medical UniversityNHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical UniversityNHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical UniversityMedical Experimental Center, General Hospital of Ningxia Medical UniversityNHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical UniversityNHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical UniversityAbstract Hyperhomocysteinemia (HHy) can lead to vascular endothelial cell dysfunction, progressive inflammation and lipid metabolism disorder, which finally result in the onset and development of atherosclerosis, a major contributor to cardiovascular diseases. Given the complexity of pathological process, treatments based on a single target often showed limited therapeutic efficacy against AS. Thus, developing nanodrug for enhanced multi-targets therapy is promising. In this study, we constructed a dual-targeting nanodrug (HA-ML@ES NPs) co-loaded with Shikonin (SKN) and Evolocumab (Evol). In vitro results showed that HA-ML@ES NPs could simultaneously target dysfunctional endothelial cell and inflammatory macrophage through the interaction between HA and CD44. In vivo assay indicated that HA-ML@ES NPs with long circulation and plaque accumulation efficiently attenuate endothelial cell dysfunction by inhibiting glycolysis and restore cholesterol flow homeostasis in macrophage by reprogramming macrophage phenotype, which finally attenuated the development of atherosclerosis. Collectively, these results present a highly promising dual-cell therapeutic approach based on HA-ML@ES NPs for the management of early atherosclerosis.https://doi.org/10.1186/s12951-025-03436-5AtherosclerosisShikoninEvolocumabEndothelial cells dysfunctionCholesterol flow homeostasis |
| spellingShingle | Qi Zhang Shengchao Ma Xue Kang Yi Liu Fei Ma Feifei Yu Xiaolan Luo Guizhong Li Yinju Hao Huiping Zhang Bin Liu Yideng Jiang A dual-targeting bio-liposomes nanodrug repair endothelial cell dysfunction and restore macrophage cholesterol flow homeostasis to treat early atherosclerosis Journal of Nanobiotechnology Atherosclerosis Shikonin Evolocumab Endothelial cells dysfunction Cholesterol flow homeostasis |
| title | A dual-targeting bio-liposomes nanodrug repair endothelial cell dysfunction and restore macrophage cholesterol flow homeostasis to treat early atherosclerosis |
| title_full | A dual-targeting bio-liposomes nanodrug repair endothelial cell dysfunction and restore macrophage cholesterol flow homeostasis to treat early atherosclerosis |
| title_fullStr | A dual-targeting bio-liposomes nanodrug repair endothelial cell dysfunction and restore macrophage cholesterol flow homeostasis to treat early atherosclerosis |
| title_full_unstemmed | A dual-targeting bio-liposomes nanodrug repair endothelial cell dysfunction and restore macrophage cholesterol flow homeostasis to treat early atherosclerosis |
| title_short | A dual-targeting bio-liposomes nanodrug repair endothelial cell dysfunction and restore macrophage cholesterol flow homeostasis to treat early atherosclerosis |
| title_sort | dual targeting bio liposomes nanodrug repair endothelial cell dysfunction and restore macrophage cholesterol flow homeostasis to treat early atherosclerosis |
| topic | Atherosclerosis Shikonin Evolocumab Endothelial cells dysfunction Cholesterol flow homeostasis |
| url | https://doi.org/10.1186/s12951-025-03436-5 |
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