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Molecules. 2019 Mar 20;24(6). pii: E1094. doi: 10.3390/molecules24061094.

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

Author information

1
Nanotechnology Characterization Lab, Frederick National Laboratory for Cancer Research Sponsored by The National Cancer Institute, Frederick, MD 21702, USA. enping@gmail.com.
2
Nanoscale Science Program, Department of Chemistry, The University of North Carolina at Charlotte, Charlotte, NC 28223, USA. jhalman@uncc.edu.
3
Nanotechnology Characterization Lab, Frederick National Laboratory for Cancer Research Sponsored by The National Cancer Institute, Frederick, MD 21702, USA. ankit.486@gmail.com.
4
Nanotechnology Characterization Lab, Frederick National Laboratory for Cancer Research Sponsored by The National Cancer Institute, Frederick, MD 21702, USA. edward.cedrone@nih.gov.
5
Nanoscale Science Program, Department of Chemistry, The University of North Carolina at Charlotte, Charlotte, NC 28223, USA. ntruong8@uncc.edu.
6
Nanoscale Science Program, Department of Chemistry, The University of North Carolina at Charlotte, Charlotte, NC 28223, USA. kafonin@uncc.edu.
7
Nanotechnology Characterization Lab, Frederick National Laboratory for Cancer Research Sponsored by The National Cancer Institute, Frederick, MD 21702, USA. marina@mail.nih.gov.

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'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' shape, size, composition, and their immunorecognition in human cells, and identified the phagolysosomal pathway as the major route for the NANPs' uptake and subsequent immunostimulation. Here, we explore the molecular mechanism of NANPs' 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.

KEYWORDS:

NANPs; Toll-like receptors; immunotoxicity; infusion reaction; interferon; nanoparticles; nucleic acids

PMID:
30897721
PMCID:
PMC6470694
DOI:
10.3390/molecules24061094
[Indexed for MEDLINE]
Free PMC Article

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