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Toll-Like Receptor-Mediated Recognition of Nucleic Acid Nanoparticles (NANPs) in Human Primary Blood Cells

  1. Author:
    Hong, Enping
    Halman, Justin R
    Shah, Ankit
    Cedrone,Edward
    Truong, Nguyen
    Afonin, Kirill A [ORCID]
    Dobrovolskaia,Marina [ORCID]

  2. Author Address

    Nanotechnology Characterization Lab, Frederick National Laboratory for Cancer Research Sponsored by The National Cancer Institute, Frederick, MD 21702, USA. enping@gmail.com., Nanoscale Science Program, Department of Chemistry, The University of North Carolina at Charlotte, Charlotte, NC 28223, USA. jhalman@uncc.edu., Nanotechnology Characterization Lab, Frederick National Laboratory for Cancer Research Sponsored by The National Cancer Institute, Frederick, MD 21702, USA. ankit.486@gmail.com., Nanotechnology Characterization Lab, Frederick National Laboratory for Cancer Research Sponsored by The National Cancer Institute, Frederick, MD 21702, USA. edward.cedrone@nih.gov., Nanoscale Science Program, Department of Chemistry, The University of North Carolina at Charlotte, Charlotte, NC 28223, USA. ntruong8@uncc.edu., Nanoscale Science Program, Department of Chemistry, The University of North Carolina at Charlotte, Charlotte, NC 28223, USA. kafonin@uncc.edu., Nanotechnology Characterization Lab, Frederick National Laboratory for Cancer Research Sponsored by The National Cancer Institute, Frederick, MD 21702, USA. marina@mail.nih.gov.,
    1. Year: 2019
    2. Date: Mar 2
    3. Epub Date: 2019 03 20
  2. Journal: Molecules (Basel, Switzerland)
    1. 24
    2. 6
    3. Pages: pii: E1094
  4. Type of Article: Article
  5. Article Number: 1094
  6. ISSN: 1420-3049
  1. Abstract:

    Infusion reactions (IRs) create a translational hurdle for many novel therapeutics, including those utilizing nanotechnology. Nucleic acid nanoparticles (NANPs) are a novel class of therapeutics prepared by rational design of relatively short oligonucleotides to self-assemble into various programmable geometric shapes. While cytokine storm, a common type of IR, has halted clinical development of several therapeutic oligonucleotides, NANP technologies hold tremendous potential to bring these reactions under control by tuning the particle 39;s physicochemical properties to the desired type and magnitude of the immune response. Recently, we reported the very first comprehensive study of the structure?activity relationship between NANPs 39; shape, size, composition, and their immunorecognition in human cells, and identified the phagolysosomal pathway as the major route for the NANPs 39; uptake and subsequent immunostimulation. Here, we explore the molecular mechanism of NANPs 39; recognition by primary immune cells, and particularly the contributing role of the Toll-like receptors. Our current study expands the understanding of the immune recognition of engineered nucleic acid-based therapeutics and contributes to the improvement of the nanomedicine safety profile.

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External Sources

  1. View Full Text
  2. DOI: 10.3390/molecules24061094
  3. PMID: 30897721
  4. View record in Web of Science®
  5. WOS: 000465503800070
  6. PII : molecules24061094

Library Notes

  1. Fiscal Year: FY2018-2019
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