Supramolecular Self-Associations of Amphiphilic Dendrons and Their Properties.
TL;DR: A detailed review of the self-association properties of dendrons can be found in this paper, where the authors present precisely defined amphiphilic dendron, their self association properties, and their different uses.
Abstract: This review presents precisely defined amphiphilic dendrons, their self-association properties, and their different uses. Dendrons, also named dendritic wedges, are composed of a core having two different types of functions, of which one type is used for growing or grafting branched arms, generally multiplied by 2 at each layer by using 1→2 branching motifs. A large diversity of structures has been already synthesized. In practically all cases, their synthesis is based on the synthesis of known dendrimers, such as poly(aryl ether), poly(amidoamine) (in particular PAMAM), poly(amide) (in particular poly(L-lysine)), 1→3 branching motifs (instead of 1→2), poly(alkyl ether) (poly(glycerol) and poly(ethylene glycol)), poly(ester), and those containing main group elements (poly(carbosilane) and poly(phosphorhydrazone)). In most cases, the hydrophilic functions are on the surface of the dendrons, whereas one or two hydrophobic tails are linked to the core. Depending on the structure of the dendrons, and on the experimental conditions used, the amphiphilic dendrons can self-associate at the air-water interface, or form micelles (eventually tubular, but most generally spherical), or form vesicles. These associated dendrons are suitable for the encapsulation of low-molecular or macromolecular bioactive entities to be delivered in cells. This review is organized depending on the nature of the internal structure of the amphiphilic dendrons (aryl ether, amidoamine, amide, quaternary carbon atom, alkyl ether, ester, main group element). The properties issued from their self-associations are described all along the review.
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TL;DR: The validation of the polycationic phosphorus dendrimer-based approach for small interfering RNAs delivery in in vitro stem-like cells as models shows 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.
Abstract: 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.
9 citations
TL;DR: This work synthesized amphiphilic triazine-phosphorus dendrons bearing multiple copper (II) or gold (III) complexes on the periphery and a branched hydrophobic fragment at the focal point to show the potential of metallodendron-based nanoformulations as antitumor entities.
Abstract: Dendritic molecules bearing metal complexes in their structure (metallodendrimers and metallodendrons) are considered prospective therapeutic entities. In particular, metallodendrons raise interest as antitumor agents for the treatment of poorly curable or drug-resistant tumors. Herein, we have synthesized amphiphilic triazine-phosphorus dendrons bearing multiple copper (II) or gold (III) complexes on the periphery and a branched hydrophobic fragment at the focal point. Due to their amphiphilic nature, metallodendrons formed single micelles (mean diameter ~9 nm) or multi-micellar aggregates (mean diameter ~60 nm) in a water solution. We have tested the antitumor activity of amphiphilic metallodendrons towards glioblastoma, a malignant brain tumor with a notoriously high level of therapy resistance, as a model disease. The metallodendrons exhibit higher cytotoxic activity towards glioblastoma stem cells (BTSC233, JHH520, NCH644, and SF188 cell lines) and U87 glioblastoma cells (IC50 was 3–6 µM for copper-containing dendron and 11–15 µM for gold-containing dendron) in comparison with temozolomide (IC50 >100 µM)—the clinical standard of care for glioblastoma. Our findings show the potential of metallodendron-based nanoformulations as antitumor entities.
4 citations
TL;DR: In this article , the most recent advances in the pharmaceutical applications of carbosilane dendritic molecules, from therapeutics to diagnostics and prevention tools, are summarized, including metallodendrimers, supramolecular assemblies, dendronized nanoparticles and surfaces.
Abstract: Dendrimers are multifunctional molecules with well-defined size and structure due to the step-by-step synthetic procedures required in their preparation. Dendritic constructs based on carbosilane scaffolds present carbon-carbon and carbon-silicon bonds, which results in stable, lipophilic, inert, and flexible structures. These properties are highly appreciated in different areas, including the pharmaceutical field, as they can increase the interaction with cell membranes and improve the therapeutic action. This article summarizes the most recent advances in the pharmaceutical applications of carbosilane dendritic molecules, from therapeutics to diagnostics and prevention tools. Dendrimers decorated with cationic, anionic, or other moieties, including metallodendrimers; supramolecular assemblies; dendronized nanoparticles and surfaces; as well as dendritic networks like hydrogels are described. The collected examples confirm the potential of carbosilane dendrimers and dendritic materials as antiviral or antibacterial agents; in therapy against cancer, neurodegenerative disease, or oxidative stress; or many other biomedical applications. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.
4 citations
TL;DR: In this article , the loading of rose bengal into vesicle-like constructs of amphiphilic triazine-carbosilane dendrons (dendrimersomes) as well as biophysical and in vitro characterization of this novel nanosystem were reported.
Abstract: The search for new formulations for photodynamic therapy is intended to improve the outcome of skin cancer treatment using significantly reduced doses of photosensitizer, thereby avoiding side effects. The incorporation of photosensitizers into nanoassemblies is a versatile way to increase the efficiency and specificity of drug delivery into target cells. Herein, we report the loading of rose bengal into vesicle-like constructs of amphiphilic triazine-carbosilane dendrons (dendrimersomes) as well as biophysical and in vitro characterization of this novel nanosystem.Using established protocol and analytical and spectroscopy techniques we were able to synthesized dendrons with strictly designed properties. Engaging biophysical methods (hydrodynamic diameter and zeta potential measurements, analysis of spectral properties, transmission electron microscopy) we confirmed assembling of our nanosystem. A set of in vitro techniques was used for determination ROS generation, (ABDA and H2DCFDA probes), cell viability (MTT assay) and cellular uptake (flow cytometry and confocal microscopy).Encapsulation of rose bengal inside dendrimersomes enhances cellular uptake, intracellular ROS production and concequently, the phototoxicity of this photosensitizer.Triazine-carbosilane dendrimersomes show high capacity as drug carriers for anticancer photodynamic therapy.
4 citations
TL;DR: In this article , polycationic dendrimers were used as carriers for microRNAs in peripheral blood mononuclear cells of healthy donors, and the treatment affected the expression of HLA-DR on T-cells and PD-1 expression on T and B-lymphocytes.
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.
3 citations
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TL;DR: Starburst polymers as mentioned in this paper are a class of topological macromolecules which are derived from classical monomers/oligomers by their extraordinary symmetry, high branching and maximized terminal functionality density.
Abstract: This paper describes the first synthesis of a new class of topological macromolecules which we refer to as “starburst polymers.” The fundamental building blocks to this new polymer class are referred to as “dendrimers.” These dendrimers differ from classical monomers/oligomers by their extraordinary symmetry, high branching and maximized (telechelic) terminal functionality density. The dendrimers possess “reactive end groups” which allow (a) controlled moelcular weight building (monodispersity), (b) controlled branching (topology), and (c) versatility in design and modification of the terminal end groups. Dendrimer synthesis is accomplished by a variety of strategies involving “time sequenced propagation” techniques. The resulting dendrimers grow in a geometrically progressive fashion as shown: Chemically bridging these dendrimers leads to the new class of macromolecules—”starburst polymers” (e.g., (A)n, (B)n, or (C)n).
3,372 citations
TL;DR: In this article, a convergent growth approach to topological macromolecules based on dendritic fragments is described, where polyether dendric fragments are prepared by starting from what will become the periphery of the molecule and progressing inward.
Abstract: The novel convergent growth approach to topological macromolecules based on dendritic fragments is described. The polyether dendritic fragments are prepared by starting from what will become the periphery of the molecule and progressing inward. In the first step, 2 mol of a benzylic bromide is condensed with the two phenolic groups of the monomer, 3,5-di-hydroxybenzyl alcohol, under phase-transfer conditions. After transformation of the benzylic alcohol functionality of the growing molecule into the corresponding bromide, the procedure is repeated with stepwise addition of the monomer followed again by activation of the benzylic site. After several generations of growth, the resulting dendritic wedges, in their benzylic bromide form, can be coupled to a polyfunctional core such as 1,1,1-tris(4{prime}-hydroxyphenyl)ethane to form the final hyperbranched macromolecule. Unique features of the convergent approach include the control over the nature and placement of the groups that are placed at the periphery of the molecule and the fact that each growth step only involves reaction at a single site of the growing macromolecule.
2,219 citations
TL;DR: The structural origin of chirality in different supramolecular structures through combinations of structural analysis methods has been investigated in this article, where the most ideal building blocks would need to display shape persistence in solution and in the solid state, since only this feature provides access to the use of complementary methods of structural analyses.
Abstract: Dendron-mediated self-assembly, disassembly, and self-organization of complex systems have been investigated. The most ideal building blocks would need to display shape persistence in solution and in the solid state, since only this feature provides access to the use of complementary methods of structural analysis. Most supramolecular dendrimers are chiral even when they are constructed from nonchiral building blocks and are equipped with mechanisms that amplify chirality. This poses additional challenges associated with the understanding of the structural origin of chirality in different supramolecular structures through combinations of structural analysis methods. While many supramolecular structures assembled from dendrimers and dendrons resemble some of the related morphologies generated from block-copolymers, they are much more complex and are not determined by the volume ratio between the dissimilar parts of the molecule.
1,061 citations
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TL;DR: It is shown that metal alloys known to defy the rules of crystallography and form so-called quasicrystals, which have rotational symmetry other than the allowed two-, three-, four- or six-fold symmetry, can also exist in the scaled-up micellar phases.
Abstract: A large number of synthetic and natural compounds self-organize into bulk phases exhibiting periodicities on the 10-8–10-6 metre scale1 as a consequence of their molecular shape, degree of amphiphilic character and, often, the presence of additional non-covalent interactions Such phases are found in lyotropic systems2 (for example, lipid–water, soap–water), in a range of block copolymers3 and in thermotropic (solvent-free) liquid crystals4 The resulting periodicity can be one-dimensional (lamellar phases), two-dimensional (columnar phases) or three dimensional (‘micellar’ or ‘bicontinuous’ phases) All such two- and three-dimensional structures identified to date obey the rules of crystallography and their symmetry can be described, respectively, by one of the 17 plane groups or 230 space groups The ‘micellar’ phases have crystallographic counterparts in transition-metal alloys, where just one metal atom is equivalent to a 103 - 104-atom micelle However, some metal alloys are known to defy the rules of crystallography and form so-called quasicrystals, which have rotational symmetry other than the allowed two-, three-, four- or six-fold symmetry5 Here we show that such quasiperiodic structures can also exist in the scaled-up micellar phases, representing a new mode of organization in soft matter
569 citations