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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MDPI AG
2022-12-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/1/148 |
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| author | Nadezhda Knauer Ekaterina Pashkina Alina Aktanova Olga Boeva Valeria Arkhipova Margarita Barkovskaya Mariya Meschaninova Andrii Karpus Jean-Pierre Majoral Vladimir Kozlov Evgeny Apartsin |
| author_facet | Nadezhda Knauer Ekaterina Pashkina Alina Aktanova Olga Boeva Valeria Arkhipova Margarita Barkovskaya Mariya Meschaninova Andrii Karpus Jean-Pierre Majoral Vladimir Kozlov Evgeny Apartsin |
| author_sort | Nadezhda Knauer |
| collection | DOAJ |
| description | 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<sup>+</sup> and CD19<sup>+</sup> 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. |
| first_indexed | 2024-03-09T11:27:13Z |
| format | Article |
| id | doaj.art-1ac73a4827ae492fb1251a011de3da79 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T11:27:13Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-1ac73a4827ae492fb1251a011de3da792023-11-30T23:58:24ZengMDPI AGPharmaceutics1999-49232022-12-0115114810.3390/pharmaceutics15010148Effects of Cationic Dendrimers and Their Complexes with microRNAs on Immunocompetent CellsNadezhda Knauer0Ekaterina Pashkina1Alina Aktanova2Olga Boeva3Valeria Arkhipova4Margarita Barkovskaya5Mariya Meschaninova6Andrii Karpus7Jean-Pierre Majoral8Vladimir Kozlov9Evgeny Apartsin10Research Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, RussiaResearch Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, RussiaResearch Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, RussiaResearch Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine SB RAS, 630090 Novosibirsk, RussiaResearch Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, RussiaLaboratoire de Chimie de Coordination, CNRS, 205 Route de Narbonne, CEDEX 04, 31077 Toulouse, FranceLaboratoire de Chimie de Coordination, CNRS, 205 Route de Narbonne, CEDEX 04, 31077 Toulouse, FranceLaboratoire de Chimie de Coordination, CNRS, 205 Route de Narbonne, CEDEX 04, 31077 Toulouse, FranceResearch Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine SB RAS, 630090 Novosibirsk, RussiaShort 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<sup>+</sup> and CD19<sup>+</sup> 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.https://www.mdpi.com/1999-4923/15/1/148dendrimersmicroRNAimmunotherapynanomedicinePBMCscytokines |
| spellingShingle | Nadezhda Knauer Ekaterina Pashkina Alina Aktanova Olga Boeva Valeria Arkhipova Margarita Barkovskaya Mariya Meschaninova Andrii Karpus Jean-Pierre Majoral Vladimir Kozlov Evgeny Apartsin Effects of Cationic Dendrimers and Their Complexes with microRNAs on Immunocompetent Cells Pharmaceutics dendrimers microRNA immunotherapy nanomedicine PBMCs cytokines |
| title | Effects of Cationic Dendrimers and Their Complexes with microRNAs on Immunocompetent Cells |
| title_full | Effects of Cationic Dendrimers and Their Complexes with microRNAs on Immunocompetent Cells |
| title_fullStr | Effects of Cationic Dendrimers and Their Complexes with microRNAs on Immunocompetent Cells |
| title_full_unstemmed | Effects of Cationic Dendrimers and Their Complexes with microRNAs on Immunocompetent Cells |
| title_short | Effects of Cationic Dendrimers and Their Complexes with microRNAs on Immunocompetent Cells |
| title_sort | effects of cationic dendrimers and their complexes with micrornas on immunocompetent cells |
| topic | dendrimers microRNA immunotherapy nanomedicine PBMCs cytokines |
| url | https://www.mdpi.com/1999-4923/15/1/148 |
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