Folic acid-modified ginger-derived extracellular vesicles for targeted treatment of rheumatoid arthritis by remodeling immune microenvironment via the PI3K-AKT pathway
Abstract Rheumatoid arthritis (RA), a form of autoimmune inflammation, is marked by enduring synovial inflammation and the subsequent impairment of joint function. Despite the availability of conventional treatments, they are often marred by significant side effects and the associated high costs. Pl...
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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/s12951-025-03096-5 |
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| author | Ruina Han Dongyang Zhou Ning Ji Zhifeng Yin Jian Wang Qin Zhang Hao Zhang Jinlong Liu Xinru Liu Han Liu Qinglin Han Jiacan Su |
| author_facet | Ruina Han Dongyang Zhou Ning Ji Zhifeng Yin Jian Wang Qin Zhang Hao Zhang Jinlong Liu Xinru Liu Han Liu Qinglin Han Jiacan Su |
| author_sort | Ruina Han |
| collection | DOAJ |
| description | Abstract Rheumatoid arthritis (RA), a form of autoimmune inflammation, is marked by enduring synovial inflammation and the subsequent impairment of joint function. Despite the availability of conventional treatments, they are often marred by significant side effects and the associated high costs. Plant-derived extracellular vesicles (PEVs) offer a compelling alternative, owing to their abundant availability, affordability, low immunogenicity, high biocompatibility, and feasibility for large-scale production. These vesicles enhance intercellular communication by transferring intrinsic bioactive molecules. In our research, we delve into the capacity of PEVs to treat RA, highlighting the role of ginger-derived extracellular vesicles (GDEVs). By conjugating GDEVs with folic acid (FA), we have developed FA-GDEVs that maintain their inherent immunomodulatory properties. FA-GDEVs are designed to selectively target M1 macrophages in inflamed joints via the folate receptors (FRs). Our in vitro findings indicate that FA-GDEVs promote the polarization towards a reparative M2 macrophage phenotype by modulating the PI3K-AKT pathway. Further corroboration comes from in vivo studies, which demonstrate that FA-GDEVs not only concentrate efficiently in the affected joints but also markedly reduce the manifestations of RA. Synthesizing these findings, it is evident that FA-GDEVs emerge as a hopeful candidate for RA treatment, offering benefits such as safety, affordability, and therapeutic efficacy. Graphical abstract |
| format | Article |
| id | doaj-art-e40dc56840db4e29aa5974df04d71d23 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-e40dc56840db4e29aa5974df04d71d232025-01-26T12:51:01ZengBMCJournal of Nanobiotechnology1477-31552025-01-0123111610.1186/s12951-025-03096-5Folic acid-modified ginger-derived extracellular vesicles for targeted treatment of rheumatoid arthritis by remodeling immune microenvironment via the PI3K-AKT pathwayRuina Han0Dongyang Zhou1Ning Ji2Zhifeng Yin3Jian Wang4Qin Zhang5Hao Zhang6Jinlong Liu7Xinru Liu8Han Liu9Qinglin Han10Jiacan Su11Institute of Translational Medicine, Shanghai UniversityInstitute of Translational Medicine, Shanghai UniversityInstitute of Translational Medicine, Shanghai UniversityDepartment of Orthopedics, Shanghai Zhongye HospitalInstitute of Translational Medicine, Shanghai UniversityInstitute of Translational Medicine, Shanghai UniversityInstitute of Translational Medicine, Shanghai UniversityInstitute of Translational Medicine, Shanghai UniversityInstitute of Translational Medicine, Shanghai UniversityInstitute of Translational Medicine, Shanghai UniversityDepartment of Orthopedics, The Affiliated Hospital of Nantong UniversityInstitute of Translational Medicine, Shanghai UniversityAbstract Rheumatoid arthritis (RA), a form of autoimmune inflammation, is marked by enduring synovial inflammation and the subsequent impairment of joint function. Despite the availability of conventional treatments, they are often marred by significant side effects and the associated high costs. Plant-derived extracellular vesicles (PEVs) offer a compelling alternative, owing to their abundant availability, affordability, low immunogenicity, high biocompatibility, and feasibility for large-scale production. These vesicles enhance intercellular communication by transferring intrinsic bioactive molecules. In our research, we delve into the capacity of PEVs to treat RA, highlighting the role of ginger-derived extracellular vesicles (GDEVs). By conjugating GDEVs with folic acid (FA), we have developed FA-GDEVs that maintain their inherent immunomodulatory properties. FA-GDEVs are designed to selectively target M1 macrophages in inflamed joints via the folate receptors (FRs). Our in vitro findings indicate that FA-GDEVs promote the polarization towards a reparative M2 macrophage phenotype by modulating the PI3K-AKT pathway. Further corroboration comes from in vivo studies, which demonstrate that FA-GDEVs not only concentrate efficiently in the affected joints but also markedly reduce the manifestations of RA. Synthesizing these findings, it is evident that FA-GDEVs emerge as a hopeful candidate for RA treatment, offering benefits such as safety, affordability, and therapeutic efficacy. Graphical abstracthttps://doi.org/10.1186/s12951-025-03096-5Rheumatoid arthritisPlant-derived extracellular vesiclesFolate receptor targetingImmune microenvironmentPI3K-AKT pathway |
| spellingShingle | Ruina Han Dongyang Zhou Ning Ji Zhifeng Yin Jian Wang Qin Zhang Hao Zhang Jinlong Liu Xinru Liu Han Liu Qinglin Han Jiacan Su Folic acid-modified ginger-derived extracellular vesicles for targeted treatment of rheumatoid arthritis by remodeling immune microenvironment via the PI3K-AKT pathway Journal of Nanobiotechnology Rheumatoid arthritis Plant-derived extracellular vesicles Folate receptor targeting Immune microenvironment PI3K-AKT pathway |
| title | Folic acid-modified ginger-derived extracellular vesicles for targeted treatment of rheumatoid arthritis by remodeling immune microenvironment via the PI3K-AKT pathway |
| title_full | Folic acid-modified ginger-derived extracellular vesicles for targeted treatment of rheumatoid arthritis by remodeling immune microenvironment via the PI3K-AKT pathway |
| title_fullStr | Folic acid-modified ginger-derived extracellular vesicles for targeted treatment of rheumatoid arthritis by remodeling immune microenvironment via the PI3K-AKT pathway |
| title_full_unstemmed | Folic acid-modified ginger-derived extracellular vesicles for targeted treatment of rheumatoid arthritis by remodeling immune microenvironment via the PI3K-AKT pathway |
| title_short | Folic acid-modified ginger-derived extracellular vesicles for targeted treatment of rheumatoid arthritis by remodeling immune microenvironment via the PI3K-AKT pathway |
| title_sort | folic acid modified ginger derived extracellular vesicles for targeted treatment of rheumatoid arthritis by remodeling immune microenvironment via the pi3k akt pathway |
| topic | Rheumatoid arthritis Plant-derived extracellular vesicles Folate receptor targeting Immune microenvironment PI3K-AKT pathway |
| url | https://doi.org/10.1186/s12951-025-03096-5 |
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