Effectively alleviate rheumatoid arthritis via maintaining redox balance, inducing macrophage repolarization and restoring homeostasis of fibroblast-like synoviocytes by metformin-derived carbon dots
Abstract Overproduction of reactive oxygen species (ROS), elevated synovial inflammation, synovial hyperplasia and fibrosis are the main characteristic of microenvironment in rheumatoid arthritis (RA). Macrophages and fibroblast-like synoviocytes (FLSs) play crucial roles in the progression of RA. H...
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BMC
2025-01-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03159-7 |
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| author | Rui Zhang Xingyu Lin Rongjie Lin Zhenbin Chen Chenfang Miao Yao Wang Xiaoqin Deng Jianlong Lin Shishui Lin Shaohuang Weng Min Chen |
| author_facet | Rui Zhang Xingyu Lin Rongjie Lin Zhenbin Chen Chenfang Miao Yao Wang Xiaoqin Deng Jianlong Lin Shishui Lin Shaohuang Weng Min Chen |
| author_sort | Rui Zhang |
| collection | DOAJ |
| description | Abstract Overproduction of reactive oxygen species (ROS), elevated synovial inflammation, synovial hyperplasia and fibrosis are the main characteristic of microenvironment in rheumatoid arthritis (RA). Macrophages and fibroblast-like synoviocytes (FLSs) play crucial roles in the progression of RA. Hence, synergistic combination of ROS scavenging, macrophage polarization from pro-inflammatory M1 phenotype towards M2 anti-inflammatory phenotype, and restoring homeostasis of FLSs will provide a promising therapeutic strategy for RA. In this study, we successfully synthesized metformin-derived carbon dots (MCDs), and investigated the antirheumatic effect in vivo and in vitro. Designed MCDs could target inflamed cells and accumulate at the inflammatory joints of collagen-induced arthritis (CIA) rats. In vivo therapeutic investigation suggested that MCDs reduced synovial inflammation and hyperplasia, ultimately prevented cartilage destruction, bone erosion, and synovial fibrosis in CIA rats. In addition, MCDs eliminated the cellular ROS in M1 phenotype macrophages in RA microenvironment through the enzyme-like catalytic activity as well as inhibiting NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome signaling pathway, effectively polarizing them into the M2 phenotype to realize the anti-inflammatory effect. Furthermore, MCDs could inhibit the proliferation, migration, and fibrosis of inflamed FLSs. Mechanistically, MCDs restored the homeostasis of FLSs while reducing the level of synovial inflammation by blocking IL-6/gp130 signaling pathway. Combined with preferable biocompatibility, MCDs offer a prospective treatment approach for RA. |
| format | Article |
| id | doaj-art-bdeea79ab69c4377812a53ec8a9baa06 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-bdeea79ab69c4377812a53ec8a9baa062025-02-02T12:41:02ZengBMCJournal of Nanobiotechnology1477-31552025-01-0123112210.1186/s12951-025-03159-7Effectively alleviate rheumatoid arthritis via maintaining redox balance, inducing macrophage repolarization and restoring homeostasis of fibroblast-like synoviocytes by metformin-derived carbon dotsRui Zhang0Xingyu Lin1Rongjie Lin2Zhenbin Chen3Chenfang Miao4Yao Wang5Xiaoqin Deng6Jianlong Lin7Shishui Lin8Shaohuang Weng9Min Chen10Department of Orthopedic Surgery, Fujian Medical University Union HospitalDepartment of Orthopedic Surgery, Fujian Medical University Union HospitalDepartment of Orthopedic Surgery, Fujian Medical University Union HospitalDepartment of Orthopedic Surgery, Fujian Medical University Union HospitalDepartment of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical UniversityDepartment of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical UniversityDepartment of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical UniversityDepartment of Orthopedic Surgery, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial HospitalDepartment of Orthopedic Surgery, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial HospitalDepartment of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical UniversityDepartment of Orthopedic Surgery, Fujian Medical University Union HospitalAbstract Overproduction of reactive oxygen species (ROS), elevated synovial inflammation, synovial hyperplasia and fibrosis are the main characteristic of microenvironment in rheumatoid arthritis (RA). Macrophages and fibroblast-like synoviocytes (FLSs) play crucial roles in the progression of RA. Hence, synergistic combination of ROS scavenging, macrophage polarization from pro-inflammatory M1 phenotype towards M2 anti-inflammatory phenotype, and restoring homeostasis of FLSs will provide a promising therapeutic strategy for RA. In this study, we successfully synthesized metformin-derived carbon dots (MCDs), and investigated the antirheumatic effect in vivo and in vitro. Designed MCDs could target inflamed cells and accumulate at the inflammatory joints of collagen-induced arthritis (CIA) rats. In vivo therapeutic investigation suggested that MCDs reduced synovial inflammation and hyperplasia, ultimately prevented cartilage destruction, bone erosion, and synovial fibrosis in CIA rats. In addition, MCDs eliminated the cellular ROS in M1 phenotype macrophages in RA microenvironment through the enzyme-like catalytic activity as well as inhibiting NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome signaling pathway, effectively polarizing them into the M2 phenotype to realize the anti-inflammatory effect. Furthermore, MCDs could inhibit the proliferation, migration, and fibrosis of inflamed FLSs. Mechanistically, MCDs restored the homeostasis of FLSs while reducing the level of synovial inflammation by blocking IL-6/gp130 signaling pathway. Combined with preferable biocompatibility, MCDs offer a prospective treatment approach for RA.https://doi.org/10.1186/s12951-025-03159-7Metformin-derived carbon dotsTreating rheumatoid arthritisRedox balanceMacrophage repolarizationFibroblast-like synoviocytesIL-6/gp130 signaling pathway |
| spellingShingle | Rui Zhang Xingyu Lin Rongjie Lin Zhenbin Chen Chenfang Miao Yao Wang Xiaoqin Deng Jianlong Lin Shishui Lin Shaohuang Weng Min Chen Effectively alleviate rheumatoid arthritis via maintaining redox balance, inducing macrophage repolarization and restoring homeostasis of fibroblast-like synoviocytes by metformin-derived carbon dots Journal of Nanobiotechnology Metformin-derived carbon dots Treating rheumatoid arthritis Redox balance Macrophage repolarization Fibroblast-like synoviocytes IL-6/gp130 signaling pathway |
| title | Effectively alleviate rheumatoid arthritis via maintaining redox balance, inducing macrophage repolarization and restoring homeostasis of fibroblast-like synoviocytes by metformin-derived carbon dots |
| title_full | Effectively alleviate rheumatoid arthritis via maintaining redox balance, inducing macrophage repolarization and restoring homeostasis of fibroblast-like synoviocytes by metformin-derived carbon dots |
| title_fullStr | Effectively alleviate rheumatoid arthritis via maintaining redox balance, inducing macrophage repolarization and restoring homeostasis of fibroblast-like synoviocytes by metformin-derived carbon dots |
| title_full_unstemmed | Effectively alleviate rheumatoid arthritis via maintaining redox balance, inducing macrophage repolarization and restoring homeostasis of fibroblast-like synoviocytes by metformin-derived carbon dots |
| title_short | Effectively alleviate rheumatoid arthritis via maintaining redox balance, inducing macrophage repolarization and restoring homeostasis of fibroblast-like synoviocytes by metformin-derived carbon dots |
| title_sort | effectively alleviate rheumatoid arthritis via maintaining redox balance inducing macrophage repolarization and restoring homeostasis of fibroblast like synoviocytes by metformin derived carbon dots |
| topic | Metformin-derived carbon dots Treating rheumatoid arthritis Redox balance Macrophage repolarization Fibroblast-like synoviocytes IL-6/gp130 signaling pathway |
| url | https://doi.org/10.1186/s12951-025-03159-7 |
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