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

1
Nanotechnology Characterization Lab, Frederick National Laboratory for Cancer Research Sponsored by The National Cancer Institute, Frederick, MD 21702, USA
2
Nanoscale Science Program, Department of Chemistry, The University of North Carolina at Charlotte, Charlotte, NC 28223, USA
*
Authors to whom correspondence should be addressed.
Molecules 2019, 24(6), 1094; https://doi.org/10.3390/molecules24061094
Received: 27 February 2019 / Revised: 12 March 2019 / Accepted: 18 March 2019 / Published: 20 March 2019
(This article belongs to the Special Issue Therapeutic Nucleic Acids: Past, Present, and Future)
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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. View Full-Text
Keywords: nanoparticles; nucleic acids; NANPs; infusion reaction; interferon; immunotoxicity; Toll-like receptors nanoparticles; nucleic acids; NANPs; infusion reaction; interferon; immunotoxicity; Toll-like receptors
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Hong, E.; Halman, J.R.; Shah, A.; Cedrone, E.; Truong, N.; Afonin, K.A.; Dobrovolskaia, M.A. Toll-Like Receptor-Mediated Recognition of Nucleic Acid Nanoparticles (NANPs) in Human Primary Blood Cells. Molecules 2019, 24, 1094.

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