Effects of Cationic Dendrimers and Their Complexes with microRNAs on Immunocompetent Cells

Short regulatory oligonucleotides are considered prospective tools for immunotherapy. However, they require an adequate carrier to deliver potential therapeutics into immune cells. Herein, we explore the potential of polycationic dendrimers as carriers for microRNAs in peripheral blood mononuclear c...

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Published inPharmaceutics Vol. 15; no. 1; p. 148
Main Authors Knauer, Nadezhda, Pashkina, Ekaterina, Aktanova, Alina, Boeva, Olga, Arkhipova, Valeria, Barkovskaya, Margarita, Meschaninova, Mariya, Karpus, Andrii, Majoral, Jean-Pierre, Kozlov, Vladimir, Apartsin, Evgeny
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 01.01.2023
MDPI
Subjects
Chemical Sciences
cytokines
dendrimers
Galenic pharmacology
Immunocompetence
Immunology
Immunotherapy
Life Sciences
microRNA
MicroRNAs
Microscopy
nanomedicine
PBMCs
Pharmaceutical sciences
Phosphorus
Polymers
United States > US
Germany
Russia
dendrimers
immunotherapy
microRNA
nanomedicine
cytokines
PBMCs
surface markers
Dendrimers
MicroRNA
Cytokines
Immunotherapy
Nanomedicine
Surface markers
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Summary:Short regulatory oligonucleotides are considered prospective tools for immunotherapy. However, they require an adequate carrier to deliver potential therapeutics into immune cells. Herein, we explore the potential of polycationic dendrimers as carriers for microRNAs in peripheral blood mononuclear cells of healthy donors. As an oligonucleotide cargo, we use a synthetic mimic and an inhibitor of miR-155, an important factor in the development and functioning of immunocompetent cells. Dendrimers bind microRNAs into low-cytotoxic polyelectrolyte complexes that are efficiently uptaken by immunocompetent cells. We have shown these complexes to affect the number of T-regulatory cells, CD14 and CD19 cell subpopulations in non-activated mononuclear cells. The treatment affected the expression of HLA-DR on T-cells and PD-1 expression on T- and B-lymphocytes. It also affected the production of IL-4 and IL-10, but not the perforin and granzyme B production. Our findings suggest the potential of dendrimer-mediated microRNA-155 treatment for immunotherapy, though the activity of microRNA-dendrimer constructions on distinct immune cell subsets can be further improved.
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ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics15010148