Activated macrophage membrane-coated nanoparticles relieve osteoarthritis-induced synovitis and joint damage
Copyright © 2023 Elsevier Ltd. All rights reserved..
Osteoarthritis (OA) is a common joint condition that is a leading cause of disability worldwide. There are currently no disease-modifying treatments for osteoarthritis, which is associated with multiple kinds of inflammatory cytokines produced by M1 macrophages in the synovium of the joint. Despite recent therapeutic advancements with anti-cytokine biologics, the OA therapy response rate continues to be inadequate. To treat OA, the pro-inflammatory and anti-inflammatory responses of synoviocytes and macrophages must be controlled simultaneously. Therefore, the immune regulation capabilities of an ideal nano-drug should not only minimize pro-inflammatory responses but also effectively boost anti-inflammatory responses. In this paper, an M2HRPK nanotherapeutic system was developed, KAFAK and shRNA-LEPR were condensed with polyethylenimine (PEI) to form a complex, which was then modified with hyaluronic acid (HA) to negatively charge to cover the M2 membrane. It was discovered that the repolarization of macrophages from the M1 to the M2 phenotype lowered pro-inflammatory responses while enhancing anti-inflammatory responses in macrophages and synoviocytes. In vitro and in vivo studies demonstrate that M2H@RPK dramatically decreases proinflammatory cytokines, controls synovial inflammation, and provides significant therapeutic efficacy by reducing joint damage. Overall, it has been demonstrated that M2H@RPK provides inflammation-targeted therapy by macrophage repolarization, and it represents a promising OA therapeutic strategy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:295 |
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| Enthalten in: |
Biomaterials - 295(2023) vom: 01. Apr., Seite 122036 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhou, Kai [VerfasserIn] |
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| Links: |
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| Themen: |
Anti-Inflammatory Agents |
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| Anmerkungen: |
Date Completed 10.03.2023 Date Revised 22.03.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.biomaterials.2023.122036 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2023 Elsevier Ltd. All rights reserved. | ||
| 520 | |a Osteoarthritis (OA) is a common joint condition that is a leading cause of disability worldwide. There are currently no disease-modifying treatments for osteoarthritis, which is associated with multiple kinds of inflammatory cytokines produced by M1 macrophages in the synovium of the joint. Despite recent therapeutic advancements with anti-cytokine biologics, the OA therapy response rate continues to be inadequate. To treat OA, the pro-inflammatory and anti-inflammatory responses of synoviocytes and macrophages must be controlled simultaneously. Therefore, the immune regulation capabilities of an ideal nano-drug should not only minimize pro-inflammatory responses but also effectively boost anti-inflammatory responses. In this paper, an M2HRPK nanotherapeutic system was developed, KAFAK and shRNA-LEPR were condensed with polyethylenimine (PEI) to form a complex, which was then modified with hyaluronic acid (HA) to negatively charge to cover the M2 membrane. It was discovered that the repolarization of macrophages from the M1 to the M2 phenotype lowered pro-inflammatory responses while enhancing anti-inflammatory responses in macrophages and synoviocytes. In vitro and in vivo studies demonstrate that M2H@RPK dramatically decreases proinflammatory cytokines, controls synovial inflammation, and provides significant therapeutic efficacy by reducing joint damage. Overall, it has been demonstrated that M2H@RPK provides inflammation-targeted therapy by macrophage repolarization, and it represents a promising OA therapeutic strategy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Cartilage damage | |
| 650 | 4 | |a Inflammatory cytokine | |
| 650 | 4 | |a Macrophage | |
| 650 | 4 | |a Synoviocyte | |
| 650 | 4 | |a Synovitis | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a Anti-Inflammatory Agents |2 NLM | |
| 700 | 1 | |a Yang, Chengli |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Kun |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yue |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Danrong |e verfasserin |4 aut | |
| 700 | 1 | |a He, Xinlong |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Yun |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, Bingyang |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Jinrong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Zongke |e verfasserin |4 aut | |
| 700 | 1 | |a Qian, Zhiyong |e verfasserin |4 aut | |
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