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

Abstract

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.

Effects of Dendrimer-microRNA Nanoformulations against Glioblastoma Stem Cells

“…The complexes were incubated in the dark for 15 min at room temperature and used for subsequent work (dendriplexes were prepared anew for each experiment). Physicochemical characteristics of complexes obtained (hydrodynamic diameter 35–45 nm; PDI 0.21–0.25; zeta potential +14 mV for AE2G3-miR complexes, +1.5 mV for BDEF33-miR complexes) were in accordance with those observed earlier [ 41 ].…”

“…As carriers, we have chosen polycationic phosphorus and carbosilane dendrimers that we had already proven to be efficient carriers of therapeutic nucleic acids into both tumor [ 38 , 67 ] and immunocompetent cells [ 25 , 31 , 33 , 41 , 67 ].…”

“…To prepare the dendriplex solutions, the oligonucleotide solutions were mixed according to the optimal charge ratios found previously [ 25 , 41 ], 10-fold cation excess was used; the RNA concentrations were 25 nM, 50 nM, 100 nM, and 150 nM. The complexes were incubated in the dark for 15 min at room temperature and used for subsequent work (dendriplexes were prepared anew for each experiment).…”

Dendrimer-Mediated Delivery of DNA and RNA Vaccines

“…Among other approaches, noteworthy is the acetylation of dendrimers, which leads to neutralization of the surface amine cationic charge, which causes dendrimer toxicity by disrupting biological membranes. It is important to note that the very process of dendrimer complexation with nucleic acids (including short oligonucleotides, miRNAs, RNA, and DNA vaccines) reduces the charge of the complex and the cytotoxicity of the dendrimer [176][177][178]. Thus, dendrimer toxicity issues can be successfully addressed using chemical and biophysical approaches.…”

Unsymmetrical Low-Generation Cationic Phosphorus Dendrimers as a Nonviral Vector to Deliver MicroRNA for Breast Cancer Therapy

“…Phosphorus dendrimers or dendrons, due to their good biocompatibility and the presence of a large number of modifiable sites on the surface and branches, have been shown to have excellent performance in drug delivery, , gene transfection ,− and drug active per se . − Their relatively convenient synthesis method also allows the development of various nanoparticulate systems to tackle a wide range of diseases. Our earlier work has shown that phosphorus dendrimers bearing pyrrolidinium or piperidinium on their surface can be used for gene delivery to treat breast cancer .…”