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Regulating copper homeostasis of tumor cells to promote cuproptosis for enhancing breast cancer immunotherapy

Author

Listed:
  • Meng Guan

    (Huazhong University of Science and Technology)

  • Kai Cheng

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Xiao-Ting Xie

    (Huazhong University of Science and Technology)

  • Yong Li

    (Huazhong University of Science and Technology)

  • Meng-Wen Ma

    (Huazhong University of Science and Technology)

  • Bin Zhang

    (Huazhong University of Science and Technology)

  • Si Chen

    (Wuhan Institute of Technology)

  • Wei Chen

    (Huazhong University of Science and Technology)

  • Bo Liu

    (Huazhong University of Science and Technology)

  • Jin-Xuan Fan

    (Huazhong University of Science and Technology)

  • Yuan-Di Zhao

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

Abstract

Cuproptosis is an emerging mode of programmed cell death for tumor suppression but sometimes gets resisted by tumor cells resist under specific mechanisms. Inhibiting copper transporter ATPase (ATP7A) was found to disrupt copper ion homeostasis, thereby enhancing the effect of cuproptosis and eventually inhibiting tumor invasion and metastasis. In this study, we develop a multifunctional nanoplatfrom based on Cu9S8 (CAPSH), designed to enhance cuproptosis in tumor cells by specifically targeting ATP7A interference, while combining thermodynamic therapy with immune effects. The release of copper ions from CAPSH and the copper homeostasis interference by siRNA cooperatively increases the concentration of copper ions in tumor cells, which induces effectively cuproptosis and activates immune responses for suppressing development and metastasis of tumor. This nanoplatform simultaneously regulates cuproptosis from both principles of onset and development, facilitating the application of cuproptosis in tumor therapy.

Suggested Citation

  • Meng Guan & Kai Cheng & Xiao-Ting Xie & Yong Li & Meng-Wen Ma & Bin Zhang & Si Chen & Wei Chen & Bo Liu & Jin-Xuan Fan & Yuan-Di Zhao, 2024. "Regulating copper homeostasis of tumor cells to promote cuproptosis for enhancing breast cancer immunotherapy," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54469-7
    DOI: 10.1038/s41467-024-54469-7
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    References listed on IDEAS

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    1. Xuexiang Han & Yiye Li & Ying Xu & Xiao Zhao & Yinlong Zhang & Xiao Yang & Yongwei Wang & Ruifang Zhao & Gregory J. Anderson & Yuliang Zhao & Guangjun Nie, 2018. "Reversal of pancreatic desmoplasia by re-educating stellate cells with a tumour microenvironment-activated nanosystem," Nature Communications, Nature, vol. 9(1), pages 1-18, December.
    2. Yifeng Lei & Lixue Tang & Yangzhouyun Xie & Yunlei Xianyu & Lingmin Zhang & Peng Wang & Yoh Hamada & Kai Jiang & Wenfu Zheng & Xingyu Jiang, 2017. "Gold nanoclusters-assisted delivery of NGF siRNA for effective treatment of pancreatic cancer," Nature Communications, Nature, vol. 8(1), pages 1-15, April.
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