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Dual asparagine-depriving nanoparticles against solid tumors

Author

Listed:
  • Yubo Shen

    (Shanghai Jiao Tong University School of Medicine)

  • Huifang Wang

    (Shanghai Jiao Tong University School of Medicine)

  • Daoxia Guo

    (Shanghai Jiao Tong University School of Medicine)

  • Jiantao Liu

    (Shanghai Normal University)

  • Jinli Sun

    (Shanghai Jiao Tong University School of Medicine)

  • Nan Chen

    (Shanghai Normal University)

  • Haiyun Song

    (Shanghai Jiao Tong University School of Medicine)

  • Xiaoyuan Ji

    (Shanghai Jiao Tong University School of Medicine)

Abstract

Depletion of circulatory asparagine (Asn) by L-asparaginase (ASNase) has been used for clinical treatment of leukemia, whereas solid tumors are unresponsive to this therapy owing to their active Asn biosynthesis. Herein, we develop a type of core-shell structured cascade-responsive nanoparticles (NPs) for sequential modulation of exogenous Asn supply and endogenous Asn production. The reactive oxygen species-sensitive NP shells disintegrate in the tumor microenvironment and liberate ASNase to scavenge extracellular Asn. The acid-labile NP cores subsequently decompose in the tumor cells and release rotenone to block intracellular Asn biosynthesis. Administration of the dual Asn-depriving NPs in murine models of triple-negative breast cancer and colorectal cancer substantially suppress the growth and epithelial-mesenchymal transition of primary and relapsed tumors, fully eradicate spontaneous and post-surgical metastasis, and confer long-term T cell memory for complete resistance to tumor rechallenge. This study represents a generalized strategy to harness amino acid depletion therapy against solid tumors.

Suggested Citation

  • Yubo Shen & Huifang Wang & Daoxia Guo & Jiantao Liu & Jinli Sun & Nan Chen & Haiyun Song & Xiaoyuan Ji, 2025. "Dual asparagine-depriving nanoparticles against solid tumors," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60798-y
    DOI: 10.1038/s41467-025-60798-y
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