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Dual rectification of metabolism abnormality in pancreatic cancer by a programmed nanomedicine

Author

Listed:
  • Bowen Wu

    (Zhengzhou University
    National Center for Nanoscience and Technology
    Henan Institute of Advanced Technology)

  • Zhiqin Wang

    (National Center for Nanoscience and Technology
    Jilin University)

  • Jingyuan Liu

    (National Center for Nanoscience and Technology)

  • Naishi Li

    (National Center for Nanoscience and Technology)

  • Xudong Wang

    (National Center for Nanoscience and Technology)

  • HaoChen Bai

    (National Center for Nanoscience and Technology)

  • Chunling Wang

    (National Center for Nanoscience and Technology)

  • Jian Shi

    (National Center for Nanoscience and Technology)

  • Saiyang Zhang

    (Zhengzhou University)

  • Jian Song

    (Zhengzhou University)

  • Yiye Li

    (National Center for Nanoscience and Technology
    University of Chinese Academy of Sciences)

  • Guangjun Nie

    (Zhengzhou University
    National Center for Nanoscience and Technology
    Henan Institute of Advanced Technology
    University of Chinese Academy of Sciences)

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and lethal malignancy characterized by dysregulated energy and stromal metabolism. It is strongly supported by activated pancreatic stellate cells (PSC) which drive excessive desmoplasia and tumor growth via metabolic crosstalk. Herein, a programmed nanosystem is designed to dual rectify the metabolism abnormalities of the PDAC cells, which overexpress glucose transporter 1(GLUT1) and CD71, and the PSC for oncotherapy. The nanosystem is based on a tumor microenvironment-responsive liposome encapsulating an NF-κB inhibitor (TPCA-1) and a CD71 aptamer-linked Glut1 siRNA. TPCA-1 reverses the activated PSC to quiescence, which hampers metabolic support of the PSC to PDAC cells and bolsters the PDAC cell-targeting delivery of the siRNA. Aerobic glycolysis and the following enhancement of oxidative phosphorylation are restrained by the nano-modulation so as to amplify anti-PDAC efficacy in an orthotopic xenograft mouse model, which implies more personalized PDAC treatment based on different energy metabolic profiles.

Suggested Citation

  • Bowen Wu & Zhiqin Wang & Jingyuan Liu & Naishi Li & Xudong Wang & HaoChen Bai & Chunling Wang & Jian Shi & Saiyang Zhang & Jian Song & Yiye Li & Guangjun Nie, 2024. "Dual rectification of metabolism abnormality in pancreatic cancer by a programmed nanomedicine," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54963-y
    DOI: 10.1038/s41467-024-54963-y
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    References listed on IDEAS

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