Near-infrared light-driven metabolic reprogramming of synoviocytes for the treatment of rheumatoid arthritis
Abstract Rheumatoid arthritis is a common autoimmune disease characterized by chronic synovial inflammation and joint destruction, primarily driven by an imbalanced cellular metabolism and inflammatory microenvironment. While gene therapy offers a promising therapeutic approach, its effectiveness is...
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| Format: | Article |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61923-7 |
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| author | Hugang Zhang Jiaxin Jia Hanyu Liu Haobo Han Quanshun Li |
| author_facet | Hugang Zhang Jiaxin Jia Hanyu Liu Haobo Han Quanshun Li |
| author_sort | Hugang Zhang |
| collection | DOAJ |
| description | Abstract Rheumatoid arthritis is a common autoimmune disease characterized by chronic synovial inflammation and joint destruction, primarily driven by an imbalanced cellular metabolism and inflammatory microenvironment. While gene therapy offers a promising therapeutic approach, its effectiveness is limited by the challenges of non-specific gene expression in healthy tissues. Here, we develop a gene delivery system (namely APPC), in which near-infrared (NIR)-responsive gold nanorods are coated with chondroitin sulfate-modified polyethyleneimine to facilitate the heat-responsive targeted delivery of heme oxygenase 1 (HO-1) gene. The APPC shows favorable transfection efficiency due to its targeting ability and significantly facilitates HO-1 expression under NIR irradiation. The combination of APPC/pHO-1 and NIR can effectively reprogram the cellular metabolism and repolarize the macrophages and fibroblast-like synoviocytes, thereby inhibiting inflammation by suppressing glycolysis. Meanwhile, APPC can specifically enhance the HO-1 expression in inflamed tissues through NIR-mediated the activation of heat shock protein 70 promoter, ensuring the precise gene expression via photothermal conversion. In a collagen-induced arthritis model, APPC/pHO-1 under NIR irradiation exhibits potent therapeutic efficacy, restoring the articular microenvironmental homeostasis and mitigating the symptoms of rheumatoid arthritis. These findings highlight the potential of APPC/pHO-1 nanoparticles in the gene therapy of rheumatoid arthritis and other inflammatory diseases. |
| format | Article |
| id | doaj-art-ad5f5f461c2f48318cdcc005e253ff08 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-ad5f5f461c2f48318cdcc005e253ff082025-08-20T03:46:15ZengNature PortfolioNature Communications2041-17232025-07-0116112110.1038/s41467-025-61923-7Near-infrared light-driven metabolic reprogramming of synoviocytes for the treatment of rheumatoid arthritisHugang Zhang0Jiaxin Jia1Hanyu Liu2Haobo Han3Quanshun Li4Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin UniversityKey Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin UniversityKey Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin UniversityKey Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin UniversityKey Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin UniversityAbstract Rheumatoid arthritis is a common autoimmune disease characterized by chronic synovial inflammation and joint destruction, primarily driven by an imbalanced cellular metabolism and inflammatory microenvironment. While gene therapy offers a promising therapeutic approach, its effectiveness is limited by the challenges of non-specific gene expression in healthy tissues. Here, we develop a gene delivery system (namely APPC), in which near-infrared (NIR)-responsive gold nanorods are coated with chondroitin sulfate-modified polyethyleneimine to facilitate the heat-responsive targeted delivery of heme oxygenase 1 (HO-1) gene. The APPC shows favorable transfection efficiency due to its targeting ability and significantly facilitates HO-1 expression under NIR irradiation. The combination of APPC/pHO-1 and NIR can effectively reprogram the cellular metabolism and repolarize the macrophages and fibroblast-like synoviocytes, thereby inhibiting inflammation by suppressing glycolysis. Meanwhile, APPC can specifically enhance the HO-1 expression in inflamed tissues through NIR-mediated the activation of heat shock protein 70 promoter, ensuring the precise gene expression via photothermal conversion. In a collagen-induced arthritis model, APPC/pHO-1 under NIR irradiation exhibits potent therapeutic efficacy, restoring the articular microenvironmental homeostasis and mitigating the symptoms of rheumatoid arthritis. These findings highlight the potential of APPC/pHO-1 nanoparticles in the gene therapy of rheumatoid arthritis and other inflammatory diseases.https://doi.org/10.1038/s41467-025-61923-7 |
| spellingShingle | Hugang Zhang Jiaxin Jia Hanyu Liu Haobo Han Quanshun Li Near-infrared light-driven metabolic reprogramming of synoviocytes for the treatment of rheumatoid arthritis Nature Communications |
| title | Near-infrared light-driven metabolic reprogramming of synoviocytes for the treatment of rheumatoid arthritis |
| title_full | Near-infrared light-driven metabolic reprogramming of synoviocytes for the treatment of rheumatoid arthritis |
| title_fullStr | Near-infrared light-driven metabolic reprogramming of synoviocytes for the treatment of rheumatoid arthritis |
| title_full_unstemmed | Near-infrared light-driven metabolic reprogramming of synoviocytes for the treatment of rheumatoid arthritis |
| title_short | Near-infrared light-driven metabolic reprogramming of synoviocytes for the treatment of rheumatoid arthritis |
| title_sort | near infrared light driven metabolic reprogramming of synoviocytes for the treatment of rheumatoid arthritis |
| url | https://doi.org/10.1038/s41467-025-61923-7 |
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