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Hypoxia-tropic delivery of nanozymes targeting transferrin receptor 1 for nasopharyngeal carcinoma radiotherapy sensitization

Author

Listed:
  • Ruofei Zhang

    (Chinese Academy of Sciences)

  • Yanfang Shen

    (Sun Yat-sen University
    Sun Yat-sen University)

  • Xiaoying Zhou

    (Guangxi Medical University, Ministry of Education)

  • Jianru Li

    (Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Hanqing Zhao

    (Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Zixia Zhang

    (Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Jun Zhao

    (Guangxi Medical University, Ministry of Education)

  • Hongjun Jin

    (Sun Yat-sen University)

  • Shuanshuan Guo

    (The Fifth Affiliated Hospital of Sun Yat-Sen University)

  • Hui Ding

    (Shenzhen Second People’s Hospital/the First Affiliated Hospital of Shenzhen University Health Science Center)

  • Guohui Nie

    (Shenzhen Second People’s Hospital/the First Affiliated Hospital of Shenzhen University Health Science Center)

  • Zhe Zhang

    (First Affiliated Hospital of Guangxi Medical University)

  • Ying Wang

    (Sun Yat-sen University)

  • Xiyun Yan

    (Chinese Academy of Sciences
    Chinese Academy of Sciences
    Henan Academy of Innovations in Medical Science)

  • Kelong Fan

    (Chinese Academy of Sciences
    Chinese Academy of Sciences
    Henan Academy of Innovations in Medical Science)

Abstract

Nasopharyngeal carcinoma (NPC), a malignancy highly prevalent in East and Southeast Asia, is primarily treated with radiotherapy (RT). However, hypoxia-induced radioresistance presents a significant challenge. Nanozymes, nanomaterials with catalase-like activity, have emerged as a promising strategy for radiosensitization by converting elevated hydrogen peroxide in the tumor microenvironment into oxygen. Despite their potential, effectively targeting hypoxic lesions has been difficult. Here, we identify transferrin receptor 1 (TfR1) as an upregulated target in NPC, with its expression levels positively correlated with hypoxia. Human heavy-chain ferritin, a specific ligand of TfR1, selectively recognizes hypoxic NPC lesions in preclinical models. Based on these findings, we design a hypoxia-targeted nanozyme by loading platinum nanoparticles into ferritin. This nanozyme exhibits enhanced catalase-like activity and effectively alleviates tumor hypoxia in NPC xenografts. When combined with RT, a single injection of the nanozyme significantly inhibits tumor growth and prolongs mouse survival, outperforming sodium glycididazole, a clinically used radiosensitizer. In summary, our findings highlight TfR1 as an accessible cell surface target in hypoxic NPC lesions. The nanozyme targeting TfR1 holds promise for enhancing the therapeutic effectiveness of RT in NPC through an in situ oxygen-generation mechanism.

Suggested Citation

  • Ruofei Zhang & Yanfang Shen & Xiaoying Zhou & Jianru Li & Hanqing Zhao & Zixia Zhang & Jun Zhao & Hongjun Jin & Shuanshuan Guo & Hui Ding & Guohui Nie & Zhe Zhang & Ying Wang & Xiyun Yan & Kelong Fan, 2025. "Hypoxia-tropic delivery of nanozymes targeting transferrin receptor 1 for nasopharyngeal carcinoma radiotherapy sensitization," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56134-z
    DOI: 10.1038/s41467-025-56134-z
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    References listed on IDEAS

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    1. Linda Celeste Montemiglio & Claudia Testi & Pierpaolo Ceci & Elisabetta Falvo & Martina Pitea & Carmelinda Savino & Alessandro Arcovito & Giovanna Peruzzi & Paola Baiocco & Filippo Mancia & Alberto Bo, 2019. "Cryo-EM structure of the human ferritin–transferrin receptor 1 complex," Nature Communications, Nature, vol. 10(1), pages 1-8, December.
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