Dendriplex-Impregnated Hydrogels With Programmed Release Rate

Apartsin, Evgeny; Venyaminova, Alya G.; Majoral, Jean‐Pierre; Caminade, Anne‐Marie

doi:10.3389/fchem.2021.780608

Cited by 6 publications

(9 citation statements)

References 61 publications

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“…The complexation protocols were optimized in such a way as to fully bind RNA in samples and saturate it with cationic carriers [ 19 ]. The dendriplexes formed usually have a spherical shape and compact morphology [ 20 , 27 ]. The size of dendriplexes (30–50 nm) as well as their charge (cationic for AE2G3-containing ones and slightly cationic for BDEF33-containing ones) ( Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…Dendrimers containing main group elements in the core or as branching points have demonstrated excellent chemical stability and good biocompatibility acceptable for biomedical applications. Polycationic dendrimers of phosphorus-based or silicon-based architecture have been shown to serve as efficient transporters of therapeutic oligonucleotide constructions [ 12 , 19 , 20 , 21 ]. Their unique characteristics permit to achieve the transfection of highly complex biological objects, namely immune cells—a highly heterogenous population including cell types known to be poorly transfectable by commonly used agents.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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“…Herein, we used the cationic phosphorus dendrimer AE2G3 ( Figure 1 ), which was previously demonstrated to bind pro-apoptotic siRNAs providing efficient uptake of complexes by HeLa cells. Importantly, the siRNA binding by AE2G3 dendrimers is reversible, and complexes are able to dissociate spontaneously upon long incubation [ 19 ]. siRNA-dendrimer polyelectrolyte complexes (dendriplexes) induced apoptosis in tumor cells that resulted in the sharp decrease of viability [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

“…Cationic phosphorus dendrimers, i.e., dendrimers containing phosphorus atoms as core and branching points, show promise for the antitumor therapy as carriers for therapeutic oligonucleotides and also as bioactive entities both as agents for drug delivery [ 9 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ] and as nanodrugs per se [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. The former option is realized due to the presence of multiple cationic groups on the periphery of dendritic molecules that provide efficient oligonucleotide binding and protection against serum nucleases.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Validation of the Therapeutic Potential of Dendrimer-Based Nanoformulations against Tumor Stem Cells

Knauer

Arkhipova

et al. 2022

IJMS

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Tumor cells with stem cell properties are considered to play major roles in promoting the development and malignant behavior of aggressive cancers. Therapeutic strategies that efficiently eradicate such tumor stem cells are of highest clinical need. Herein, we performed the validation of the polycationic phosphorus dendrimer-based approach for small interfering RNAs delivery in in vitro stem-like cells as models. As a therapeutic target, we chose Lyn, a member of the Src family kinases as an example of a prominent enzyme class widely discussed as a potent anti-cancer intervention point. Our selection is guided by our discovery that Lyn mRNA expression level in glioma, a class of brain tumors, possesses significant negative clinical predictive value, promoting its potential as a therapeutic target for future molecular-targeted treatments. We then showed that anti-Lyn siRNA, delivered into Lyn-expressing glioma cell model reduces the cell viability, a fact that was not observed in a cell model that lacks Lyn-expression. Furthermore, we have found that the dendrimer itself influences various parameters of the cells such as the expression of surface markers PD-L1, TIM-3 and CD47, targets for immune recognition and other biological processes suggested to be regulating glioblastoma cell invasion. Our findings prove the potential of dendrimer-based platforms for therapeutic applications, which might help to eradicate the population of cancer cells with augmented chemotherapy resistance. Moreover, the results further promote our functional stem cell technology as suitable component in early stage drug development.

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“…This is especially important for designing local drug delivery systems and tissue engineering tools. It is also worth noting that oligonucleotides were released from a hydrogel not as individual molecules but as dendriplexes, which would facilitate their accumulation in cells of a surrounding tissue [31]. [25].…”

Section: Phosphorus Dendrimers In Hydrogelsmentioning

confidence: 99%

Single-Component Physical Hydrogels of Dendritic Molecules

Apartsin

Caminade

2023

J. Compos. Sci.

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Hydrogels are hydrophilic, three-dimensional networks able to imprison large amounts of water and are largely used in pharmaceutical formulations. Hydrogels are frequently obtained from hydrophilic polymers, either natural, biohybrid, or synthetic. Owing to their peculiar structure, dendrimers can be considered prospective building blocks for hydrogel networks. This review gathers the use of different types of amphiphilic dendritic structures able to generate physical hydrogels alone. Such dendritic structures comprise dendrimers, Janus dendrimers, and dendrons. The first part concerns different types of positively charged phosphorus dendrimers used to generate hydrogels, which are also suitable to form fibers, and for encapsulating diverse substances, or forming complexes with genetic materials for their slow delivery. The second part concerns PAMAM dendrimers functionalized with collagen mimetics. The third part concerns amphiphilic Janus dendrimers, whereas the fourth part displays different types of amphiphilic dendrons and their use, in particular in the fields of materials and drug delivery.

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Dendriplex-Impregnated Hydrogels With Programmed Release Rate

Cited by 6 publications

References 61 publications

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

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

In Vitro Validation of the Therapeutic Potential of Dendrimer-Based Nanoformulations against Tumor Stem Cells

Single-Component Physical Hydrogels of Dendritic Molecules

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