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Near-infrared light-driven metabolic reprogramming of synoviocytes for the treatment of rheumatoid arthritis

Author

Listed:
  • Hugang Zhang

    (Jilin University)

  • Jiaxin Jia

    (Jilin University)

  • Hanyu Liu

    (Jilin University)

  • Haobo Han

    (Jilin University)

  • Quanshun Li

    (Jilin University
    Jilin University)

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.

Suggested Citation

  • Hugang Zhang & Jiaxin Jia & Hanyu Liu & Haobo Han & Quanshun Li, 2025. "Near-infrared light-driven metabolic reprogramming of synoviocytes for the treatment of rheumatoid arthritis," Nature Communications, Nature, vol. 16(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61923-7
    DOI: 10.1038/s41467-025-61923-7
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    References listed on IDEAS

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    1. Zhangyi Luo & Yixian Huang & Neelu Batra & Yuang Chen & Haozhe Huang & Yifei Wang & Ziqian Zhang & Shichen Li & Chien-Yu Chen & Zehua Wang & Jingjing Sun & Qiming Jane Wang & Da Yang & Binfeng Lu & Ja, 2024. "Inhibition of iRhom1 by CD44-targeting nanocarrier for improved cancer immunochemotherapy," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Haobo Han & Jiakai Xing & Wenqi Chen & Jiaxin Jia & Quanshun Li, 2023. "Fluorinated polyamidoamine dendrimer-mediated miR-23b delivery for the treatment of experimental rheumatoid arthritis in rats," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    3. Takehiro Yamamoto & Naoharu Takano & Kyoko Ishiwata & Mitsuyo Ohmura & Yoshiko Nagahata & Tomomi Matsuura & Aki Kamata & Kyoko Sakamoto & Tsuyoshi Nakanishi & Akiko Kubo & Takako Hishiki & Makoto Suem, 2014. "Reduced methylation of PFKFB3 in cancer cells shunts glucose towards the pentose phosphate pathway," Nature Communications, Nature, vol. 5(1), pages 1-16, May.
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