IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-02915-8.html
   My bibliography  Save this article

Targeted production of reactive oxygen species in mitochondria to overcome cancer drug resistance

Author

Listed:
  • Hai Wang

    (The Ohio State University
    The Ohio State University
    The Ohio State University)

  • Zan Gao

    (University of Virginia)

  • Xuanyou Liu

    (University of Missouri School of Medicine)

  • Pranay Agarwal

    (The Ohio State University
    The Ohio State University)

  • Shuting Zhao

    (The Ohio State University
    The Ohio State University)

  • Daniel W. Conroy

    (The Ohio State University)

  • Guang Ji

    (Shanghai University of Traditional Chinese Medicine)

  • Jianhua Yu

    (The Ohio State University
    The Ohio State University)

  • Christopher P. Jaroniec

    (The Ohio State University)

  • Zhenguo Liu

    (The Ohio State University
    University of Missouri School of Medicine)

  • Xiongbin Lu

    (Indiana University School of Medicine)

  • Xiaodong Li

    (University of Virginia)

  • Xiaoming He

    (The Ohio State University
    The Ohio State University
    The Ohio State University
    University of Maryland)

Abstract

Multidrug resistance is a major challenge to cancer chemotherapy. The multidrug resistance phenotype is associated with the overexpression of the adenosine triphosphate (ATP)-driven transmembrane efflux pumps in cancer cells. Here, we report a lipid membrane-coated silica-carbon (LSC) hybrid nanoparticle that targets mitochondria through pyruvate, to specifically produce reactive oxygen species (ROS) in mitochondria under near-infrared (NIR) laser irradiation. The ROS can oxidize the NADH into NAD+ to reduce the amount of ATP available for the efflux pumps. The treatment with LSC nanoparticles and NIR laser irradiation also reduces the expression and increases the intracellular distribution of the efflux pumps. Consequently, multidrug-resistant cancer cells lose their multidrug resistance capability for at least 5 days, creating a therapeutic window for chemotherapy. Our in vivo data show that the drug-laden LSC nanoparticles in combination with NIR laser treatment can effectively inhibit the growth of multidrug-resistant tumors with no evident systemic toxicity.

Suggested Citation

  • Hai Wang & Zan Gao & Xuanyou Liu & Pranay Agarwal & Shuting Zhao & Daniel W. Conroy & Guang Ji & Jianhua Yu & Christopher P. Jaroniec & Zhenguo Liu & Xiongbin Lu & Xiaodong Li & Xiaoming He, 2018. "Targeted production of reactive oxygen species in mitochondria to overcome cancer drug resistance," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-02915-8
    DOI: 10.1038/s41467-018-02915-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-02915-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-02915-8?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
    ---><---

    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_s41467-018-02915-8. 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.