IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-05906-x.html
   My bibliography  Save this article

Reversal of pancreatic desmoplasia by re-educating stellate cells with a tumour microenvironment-activated nanosystem

Author

Listed:
  • Xuexiang Han

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

  • Yiye Li

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

  • Ying Xu

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

  • Xiao Zhao

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

  • Yinlong Zhang

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

  • Xiao Yang

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

  • Yongwei Wang

    (Chinese Academy of Sciences)

  • Ruifang Zhao

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

  • Gregory J. Anderson

    (Royal Brisbane Hospital)

  • Yuliang Zhao

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

  • Guangjun Nie

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

Abstract

Pancreatic ductal adenocarcinoma is characterised by a dense desmoplastic stroma composed of stromal cells and extracellular matrix (ECM). This barrier severely impairs drug delivery and penetration. Activated pancreatic stellate cells (PSCs) play a key role in establishing this unique pathological obstacle, but also offer a potential target for anti-tumour therapy. Here, we construct a tumour microenvironment-responsive nanosystem, based on PEGylated polyethylenimine-coated gold nanoparticles, and utilise it to co-deliver all-trans retinoic acid (ATRA, an inducer of PSC quiescence) and siRNA targeting heat shock protein 47 (HSP47, a collagen-specific molecular chaperone) to re-educate PSCs. The nanosystem simultaneously induces PSC quiescence and inhibits ECM hyperplasia, thereby promoting drug delivery to pancreatic tumours and significantly enhancing the anti-tumour efficacy of chemotherapeutics. Our combination strategy to restore homoeostatic stromal function by targeting activated PSCs represents a promising approach to improving the efficacy of chemotherapy and other therapeutic modalities in a wide range of stroma-rich tumours.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05906-x
    DOI: 10.1038/s41467-018-05906-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-05906-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-05906-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Xuexiang Han & Ningqiang Gong & Lulu Xue & Margaret M. Billingsley & Rakan El-Mayta & Sarah J. Shepherd & Mohamad-Gabriel Alameh & Drew Weissman & Michael J. Mitchell, 2023. "Ligand-tethered lipid nanoparticles for targeted RNA delivery to treat liver fibrosis," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Jingchao Li & Yu Luo & Ziling Zeng & Dong Cui & Jiaguo Huang & Chenjie Xu & Liping Li & Kanyi Pu & Ruiping Zhang, 2022. "Precision cancer sono-immunotherapy using deep-tissue activatable semiconducting polymer immunomodulatory nanoparticles," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Xin Li & Tuying Yong & Zhaohan Wei & Nana Bie & Xiaoqiong Zhang & Guiting Zhan & Jianye Li & Jiaqi Qin & Jingjing Yu & Bixiang Zhang & Lu Gan & Xiangliang Yang, 2022. "Reversing insufficient photothermal therapy-induced tumor relapse and metastasis by regulating cancer-associated fibroblasts," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05906-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.