IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_s41467-017-01386-7.html
   My bibliography  Save this article

Intertwining DNA-RNA nanocapsules loaded with tumor neoantigens as synergistic nanovaccines for cancer immunotherapy

Author

Listed:
  • Guizhi Zhu

    (National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH))

  • Lei Mei

    (College of Agriculture and Natural Resources, University of Maryland)

  • Harshad D. Vishwasrao

    (Advanced Imaging and Microscopy Resource, NIH)

  • Orit Jacobson

    (National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH))

  • Zhantong Wang

    (National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH))

  • Yijing Liu

    (National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH))

  • Bryant C. Yung

    (National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH))

  • Xiao Fu

    (Laboratory of Cellular Imaging and Macromolecular Biophysics, NIBIB, NIH)

  • Albert Jin

    (Laboratory of Cellular Imaging and Macromolecular Biophysics, NIBIB, NIH)

  • Gang Niu

    (National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH))

  • Qin Wang

    (College of Agriculture and Natural Resources, University of Maryland)

  • Fuwu Zhang

    (National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH))

  • Hari Shroff

    (Advanced Imaging and Microscopy Resource, NIH
    Section on High Resolution Optical Imaging, NIBIB, NIH)

  • Xiaoyuan Chen

    (National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH))

Abstract

Nanomedicines that co-deliver DNA, RNA, and peptide therapeutics are highly desirable yet remain underdeveloped for cancer theranostics. Herein, we report self-assembled intertwining DNA-RNA nanocapsules (iDR-NCs) that efficiently delivered synergistic DNA CpG and short hairpin RNA (shRNA) adjuvants, as well as tumor-specific peptide neoantigens into antigen presenting cells (APCs) in lymph nodes for cancer immunotherapy. These nanovaccines were prepared by (1) producing tandem CpG and shRNA via concurrent rolling circle replication and rolling circle transcription, (2) self-assembling CpG and shRNA into DNA-RNA microflowers, (3) shrinking microflowers into iDR-NCs using PEG-grafted cationic polypeptides, and (4) physically loading neoantigen into iDR-NCs. CpG and shRNA in iDR-NCs synergistically activate APCs for sustained antigen presentation. Remarkably, iDR-NC/neoantigen nanovaccines elicit 8-fold more frequent neoantigen-specific peripheral CD8+ T cells than CpG, induce T cell memory, and significantly inhibit the progression of neoantigen-specific colorectal tumors. Collectively, iDR-NCs represent potential DNA/RNA/peptide triple-co-delivery nanocarriers and synergistic tumor immunotherapeutic nanovaccines.

Suggested Citation

  • Guizhi Zhu & Lei Mei & Harshad D. Vishwasrao & Orit Jacobson & Zhantong Wang & Yijing Liu & Bryant C. Yung & Xiao Fu & Albert Jin & Gang Niu & Qin Wang & Fuwu Zhang & Hari Shroff & Xiaoyuan Chen, 2017. "Intertwining DNA-RNA nanocapsules loaded with tumor neoantigens as synergistic nanovaccines for cancer immunotherapy," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01386-7
    DOI: 10.1038/s41467-017-01386-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-017-01386-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-017-01386-7?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:8:y:2017:i:1:d:10.1038_s41467-017-01386-7. 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.