The Recognition of and Reactions to Nucleic Acid Nanoparticles by Human Immune Cells

Abstract

The relatively straightforward methods of designing and assembling various functional nucleic acids into nanoparticles offer advantages for applications in diverse diagnostic and therapeutic approaches. However, due to the novelty of this approach, nucleic acid nanoparticles (NANPs) are not yet used in the clinic. The immune recognition of NANPs is among the areas of preclinical investigation aimed at enabling the translation of these novel materials into clinical settings. NANPs’ interactions with the complement system, coagulation systems, and immune cells are essential components of their preclinical safety portfolio. It has been established that NANPs’ physicochemical properties—composition, shape, and size—determine their interactions with immune cells (primarily blood plasmacytoid dendritic cells and monocytes), enable recognition by pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) and RIG-I-like receptors (RLRs), and mediate the subsequent cytokine response. However, unlike traditional therapeutic nucleic acids (e.g., CpG oligonucleotides), NANPs do not trigger a cytokine response unless they are delivered into the cells using a carrier. Recently, it was discovered that the type of carrier provides an additional tool for regulating both the spectrum and the magnitude of the cytokine response to NANPs. Herein, we review the current knowledge of NANPs’ interactions with various components of the immune system to emphasize the unique properties of these nanomaterials and highlight opportunities for their use in vaccines and immunotherapy.

Green Synthesis of Silver Nanoparticles Using Natural Extracts with Proven Antioxidant Activity

“…Currently, nanoparticles belong to highly advanced and specialized biomedical products [ 1 ]. There are several interesting applications of nanoparticles in medicine and pharmacy: for example, in medical imaging, as nanocomposites, filters, components of drug delivery systems, and formulations for the treatment of cancer [ 2 , 3 , 4 , 5 ]. Gold nanoparticles have found applications in analytical procedures for the detection of cancer cells, proteins, and antibodies.…”

Therapeutic immunomodulation by rationally designed nucleic acids and nucleic acid nanoparticles

“…Cationic lipids and liposomes have been extensively explored as carriers for TNAs and can also serve as viable carrier options for NANPs. The transfection reagents lipofectamine and DOTAP have been previously employed to deliver NANPs to non-immune and immune cells ( 106 , 108 , 109 ). However, the use of Lipofectamine 2000 as a carrier is limited to in vitro cell delivery.…”

Critical review of nucleic acid nanotechnology to identify gaps and inform a strategy for accelerated clinical translation

“…Understanding how NANPs interact with the immune system will enable tailoring formulations for maximal therapeutic efficacy, while minimizing undesirable immunostimulation and adverse immune-mediated effects. Recent studies have already elucidated key factors about these interactions, including that type I and III interferons serve as reproducible biomarkers of NANP immunorecognition; the quality of the immune response to NANPs depends on their delivery into blood cells by a carrier via the endolysosomal pathway mediated by scavenger and Toll-like Receptors; plasmacytoid dendritic cells are the primary source of NANP-induced interferons in human PBMCs; and physicochemical characteristics appear to determine the magnitude of the immune response [13] , [19] , [28] , [31] , [33] , [34] , [35] , [36] , [53] , [79] . These properties reveal the opportunity to explore nucleic acid nanotechnology for vaccines and immunotherapies, with NANPs to be designed explicitly as independent therapeutic entities, and highlight the potential safety concerns should such nanomaterials reach systemic circulation and activate blood leukocytes.…”