Therapy of rheumatoid arthritis by reactive oxygen species-responsive celastrol-loaded nanomedicines via targeting macrophages apoptosis
Inflammatory cascade is a prevalent and lethal adverse event that severely affects rheumatoid arthritis (RA) patients receiving clinic therapeutics. It is correlated with the response to macrophages caused by reactive oxygen species (ROS). Currently, ROS-targeted treatment is a potential strategy th...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Materials & Design |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0264127522009200 |
| _version_ | 1811183850249781248 |
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| author | Sen Lin Dahao Wang Chang Xu Peng Zhang Kai Gao Chang Liu Xifan Mei |
| author_facet | Sen Lin Dahao Wang Chang Xu Peng Zhang Kai Gao Chang Liu Xifan Mei |
| author_sort | Sen Lin |
| collection | DOAJ |
| description | Inflammatory cascade is a prevalent and lethal adverse event that severely affects rheumatoid arthritis (RA) patients receiving clinic therapeutics. It is correlated with the response to macrophages caused by reactive oxygen species (ROS). Currently, ROS-targeted treatment is a potential strategy that can reduce the risk of RA-related obvious adverse effects, but at the cost of therapeutic efficacy. Herein, we reported folic acid (FA) modified ROS-responsive celastrol (Cel)-loaded (Cel/FA-Oxi-βCD NPs) that can release RA symptoms without chemotherapeutic agents and validated anti-inflammatory effect. In vitro study, NPs can be effectively internalized by activated macrophages and the released Cel from NPs significantly induced apoptosis in activated RAW264.7, indicating that Cel/FA-Oxi-βCD NPs remodeled the macrophages polarization homeostasis for the protection of inflamed joint microenvironment. Moreover, Cel/FA-Oxi-βCD NPs significantly decreased proinflammatory cytokines levels in serum, synovial and cartilage in collagen-induced arthritis (CIA) rats, and alleviated synovitis and cartilage destruction with excellent biocompatibility. Collectively, Cel/FA-Oxi-βCD NPs incorporated with ROS-responsive pro-apoptotic activity in macrophages, hold a great potential for clinical treatment of RA. |
| first_indexed | 2024-04-11T13:04:47Z |
| format | Article |
| id | doaj.art-33782f25972242bfa6d356ea9025a89f |
| institution | Directory Open Access Journal |
| issn | 0264-1275 |
| language | English |
| last_indexed | 2024-04-11T13:04:47Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials & Design |
| spelling | doaj.art-33782f25972242bfa6d356ea9025a89f2022-12-22T04:22:50ZengElsevierMaterials & Design0264-12752022-12-01224111298Therapy of rheumatoid arthritis by reactive oxygen species-responsive celastrol-loaded nanomedicines via targeting macrophages apoptosisSen Lin0Dahao Wang1Chang Xu2Peng Zhang3Kai Gao4Chang Liu5Xifan Mei6Department of Orthopedic, Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, China; Key Laboratory of Medical Tissue Engineering, Jinzhou Medical University, Jinzhou, ChinaDepartment of Orthopedic, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, ChinaDepartment of Orthopedic, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, ChinaDepartment of Orthopedic, Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, China; Key Laboratory of Medical Tissue Engineering, Jinzhou Medical University, Jinzhou, ChinaDepartment of Orthopedics, Jining No. 1 People's Hospital, Jining, China; Corresponding authors at: Department of Orthopedic, Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, China (X. Mei).Department of Endocrinology, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China; Corresponding authors at: Department of Orthopedic, Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, China (X. Mei).Department of Orthopedic, Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, China; Key Laboratory of Medical Tissue Engineering, Jinzhou Medical University, Jinzhou, China; Corresponding authors at: Department of Orthopedic, Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, China (X. Mei).Inflammatory cascade is a prevalent and lethal adverse event that severely affects rheumatoid arthritis (RA) patients receiving clinic therapeutics. It is correlated with the response to macrophages caused by reactive oxygen species (ROS). Currently, ROS-targeted treatment is a potential strategy that can reduce the risk of RA-related obvious adverse effects, but at the cost of therapeutic efficacy. Herein, we reported folic acid (FA) modified ROS-responsive celastrol (Cel)-loaded (Cel/FA-Oxi-βCD NPs) that can release RA symptoms without chemotherapeutic agents and validated anti-inflammatory effect. In vitro study, NPs can be effectively internalized by activated macrophages and the released Cel from NPs significantly induced apoptosis in activated RAW264.7, indicating that Cel/FA-Oxi-βCD NPs remodeled the macrophages polarization homeostasis for the protection of inflamed joint microenvironment. Moreover, Cel/FA-Oxi-βCD NPs significantly decreased proinflammatory cytokines levels in serum, synovial and cartilage in collagen-induced arthritis (CIA) rats, and alleviated synovitis and cartilage destruction with excellent biocompatibility. Collectively, Cel/FA-Oxi-βCD NPs incorporated with ROS-responsive pro-apoptotic activity in macrophages, hold a great potential for clinical treatment of RA.http://www.sciencedirect.com/science/article/pii/S0264127522009200Rheumatoid arthritisReactive oxygen speciesMacrophagesApoptosisNanotherapy |
| spellingShingle | Sen Lin Dahao Wang Chang Xu Peng Zhang Kai Gao Chang Liu Xifan Mei Therapy of rheumatoid arthritis by reactive oxygen species-responsive celastrol-loaded nanomedicines via targeting macrophages apoptosis Materials & Design Rheumatoid arthritis Reactive oxygen species Macrophages Apoptosis Nanotherapy |
| title | Therapy of rheumatoid arthritis by reactive oxygen species-responsive celastrol-loaded nanomedicines via targeting macrophages apoptosis |
| title_full | Therapy of rheumatoid arthritis by reactive oxygen species-responsive celastrol-loaded nanomedicines via targeting macrophages apoptosis |
| title_fullStr | Therapy of rheumatoid arthritis by reactive oxygen species-responsive celastrol-loaded nanomedicines via targeting macrophages apoptosis |
| title_full_unstemmed | Therapy of rheumatoid arthritis by reactive oxygen species-responsive celastrol-loaded nanomedicines via targeting macrophages apoptosis |
| title_short | Therapy of rheumatoid arthritis by reactive oxygen species-responsive celastrol-loaded nanomedicines via targeting macrophages apoptosis |
| title_sort | therapy of rheumatoid arthritis by reactive oxygen species responsive celastrol loaded nanomedicines via targeting macrophages apoptosis |
| topic | Rheumatoid arthritis Reactive oxygen species Macrophages Apoptosis Nanotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S0264127522009200 |
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