Functional Dendrimers Research Articles

Advances in functionalization and conjugation mechanisms of dendrimers with iron oxide magnetic nanoparticles.

Iron oxide magnetic nanoparticles (MNPs) are crucial in various areas due to their unique magnetic properties. However, their practical use is often limited by instability and aggregation in aqueous solutions. This review explores the advanced technique of dendrimer functionalization to enhance MNP stability and expand their application potential. Dendrimers, with their symmetric and highly branched structure, effectively stabilize MNPs and provide tailored functional sites for specific applications. We summarize key synthetic modifications, focusing on the impacts of dendrimer size, surface chemistry, and the balance of chemical (e.g., coordination, anchoring) and physical (e.g., electrostatic, hydrophobic) interactions on nanocomposite properties. Current challenges such as dendrimer toxicity, control over dendrimer distribution on MNPs, and the need for biocompatibility are discussed, alongside potential solutions involving advanced characterization techniques. This review highlights significant opportunities in environmental, biomedical, and water treatment applications, stressing the necessity for ongoing research to fully leverage dendrimer-functionalized MNPs. Insights offered here aim to guide further development and application of these promising nanocomposites.

Topological Insights into Nanostar Dendrimers by Computing the Augmented Zagreb Index.

The field of nanobiotechnology uses precise nanofabrication techniques to advance our understanding and control of biological systems. Due to their remarkable properties, dendrimers, which are hyperbranched macromolecular structures with distinct and well-defined architectures, have emerged as pivotal entities within this field. They are gaining increasing attention for their potential to catalyze a paradigm shift in medical therapeutics, biotechnological applications, and advanced material sciences. This paper focuses on a novel analytical expression and determines the precise value of the augmented Zagreb index, a topological descriptor, for eight classes of nanostar dendrimers. The Zagreb index is a topological invariant to predict molecular behaviour and reactivity. In this paper, we have explored its application in characterizing the branching of nanostar dendrimers through computational modelling and mathematical rigor. Our research has measured the augmented Zagreb index for nanostar dendrimers, which fall into eight distinct classes. The results better explain the relationship between the dendrimers' topology and chemical properties. This correlation has implications for their structural stability and reactivity, potentially leading to new applications. Developing the augmented Zagreb index for nanostar dendrimers is a significant breakthrough in nanobiotechnology. Based on the correlation between the calculated topological index and the corresponding molecular attributes, our analytical approach has opened up new possibilities for designing and synthesizing dendrimers tailored to specific functions in medical and material science applications. This precise topological quantification could significantly enhance the utility and functionalization of dendrimers in cutting-edge nanotechnological applications.

From Dendrimers to Megamers: The State-of-the-Art

Dendrimers comprise a unique type of macromolecules that are interesting from the viewpoint of both unusual architectures and the enormous application potential in high-tech fields such as nanotechnologies and nanomedicine. The only obstacle in the practical implementation of these molecules is their complicated synthesis and isolation. Therefore, the development of simple synthetic approaches to dendrimers and their derivatives is an urgent challenge that pertains to one of the most important fields of modern science, namely, the creation of nanomaterials. This review highlights the development of the methods for production and functionalization of dendrimers with a view to investigate their physico-chemical properties and outline the most promising trends such as megamers based on dendrimers. The synthesis and exploration of these molecular systems seem to be the most logical application field of dendrimers in terms of the development of our concepts about the regular polymer systems based on the principles of molecular construction.

Carboxyl or phosphate functionalization polyamidoamine dendrimer efficient scale inhibitor: Preparation and properties

Stringent water resources scarcity and severe environmental restriction requires environmentally friendly and efficient scale inhibitors exploitation. Functionalization of polyamidoamine dendrimers for scale inhibitor was performed using 2-phosphate-1, 2, 4-butane tricarboxylic acid (PBTCA) and succinic anhydride (SA). In this study, PBTCA modified polyamidoamine dendrimers (PAMAM-1), SA modified first and second generation polyamidoamine dendrimers (CAMAM-1 and CAMAM-2) are prepared. Static scale inhibition method is employed to assess the scale inhibition efficiency of linear low molecular polyacrylic (LPAA), PBTCA, PAMAM-1, CAMAM-1 and CAMAM-2 against CaCO3 and CaSO4. The results show that carboxyl terminated polyamidoamine dendrimers has excellent scale inhibition performance comparable to PBTCA and PAMAM-1. Compared to LPAA and PBTCA, dendritic structure can effectively improve the scale inhibition performance of the scale inhibitor. Furthermore, the scale inhibition performance enhances with increasing generation of carboxyl-terminated polyamidoamine dendrimer. The inhibition efficiency of CAMAM-2 against CaCO3 and CaSO4 is about 96.3% and 95.2% at a concentration of 10 mg/ L. Moreover, The CAMAM-2 performs above 85% scale inhibition at Ca2+concentration is 4000 mg/L and 90% scale inhibition at border pH 5–9. The FT-IR, XRD and SEM-EDX results show that the CaCO3 changes from stable calcite to metastable aragonite and vaterite, and the needle like structure of CaSO4 is destroyed to small crystals. CAMAM-2 only occupies the crystallization site and distorts the lattice of calcium scale in the crystal growth process rather than adsorb on the final crystal surface. This paper provides data support for the application of phosphate or carboxyl terminated polyamidoamine dendrimer in scale inhibition.

Functionalization of phenylazomethine dendrimers

Functionalization of phenylazomethine dendrimers

Synthesis and Properties of Hybrid Carbosilane Dendrimers with Cyclosiloxane External Shells

The hydrosilylation of polyallylcarbosilane dendrimers with hydride-containing six- and eight-membered dimethylcyclosiloxanes affords a series of hybrid carbosilane–siloxane dendrimers featuring different densities of the surface cyclosiloxane layers, while retaining all other molecular parameters. The main physicochemical constants of the resulting dendrimers are defined. The possibility of functionalization of these dendrimers by the opening of cyclosiloxane structural moieties in the external shell is demonstrated by the example of the zero-generation dendrimer bearing heptamethylcyclotetrasiloxane terminal groups.

Fabrication of gold nanohybrids modified with antibody and functional dendrimers for targeted photothermal theranostics

AbstractTargeted theranostics can improve benefits of therapeutics or imaging probes by minimizing the dose and by selective delivery to a target site. For this study, a gold nanorod (AuNR)‐based nanohybrid was designed for efficient cancer treatment and diagnosis. The AuNR was functionalized with polyamidoamine dendrimers having poly(ethylene glycol) and Gd‐DOTA residues to provide biocompatibility and magnetic resonance (MR) imaging properties. Furthermore, trastuzumab was conjugated to the obtained nanohybrids to enhance the delivery performance to HER2‐expressing tumor cells. Fabricated nanohybrids possessed uniform hydrodynamic diameter and showed typical surface plasmon absorption, which is useful to convert light energy to heat for photothermal therapy. Nanohybrids exhibited T1‐weighted relaxation and comparable MR imaging property to that of commercially available MR contrast reagent. In vitro experiments demonstrated that photothermal effects of nanohybrid under near infrared (NIR) irradiation were sufficient to kill 80%–90% of cancer cells. The combination of the targeted nanohybrid and NIR laser irradiation strongly suppressed tumor growth and extended the survival of HER2‐positive SKOV3 tumor‐bearing nude mice. Therefore, fabricated nanohybrids are promising for targeted photothermal therapy and imaging.

Probing sulfatide-tissue lectin recognition with functionalized glycodendrimersomes.

SummaryThe small 3-O-sulfated galactose head group of sulfatides, an abundant glycosphingolipid class, poses the (sphinx-like) riddle on involvement of glycan bridging by tissue lectins (sugar code). First, synthesis of head group derivatives for functionalization of amphiphilic dendrimers is performed. Aggregation of resulting (biomimetic) vesicles, alone or in combination with lactose, demonstrates bridging by a tissue lectin (galectin-4). Physiologically, this can stabilize glycolipid-rich microdomains (rafts) and associate sulfatide-rich regions with specific glycoproteins. Further testing documents importance of heterobivalency and linker length. Structurally, sulfatide recognition by galectin-8 is shown to involve sphingosine's OH group as substitute for the 3′-hydroxyl of glucose of lactose. These discoveries underscore functionality of this small determinant on biomembranes intracellularly and on the cell surface. Moreover, they provide a role model to examine counterreceptor capacity of more complex glycans of glycosphingolipids and to start their bottom-up glycotope surface programming.

Synthesis of Heterofunctional Polyester Dendrimers with Internal and External Functionalities as Versatile Multipurpose Platforms.

Heterofunctional dendrimers with internal and external representations of functionalities are considered as the ultimate dendritic frameworks. This is reflected by their unprecedented scaffolding, such as precise control over the structure, molecular weight, number, and location of different cargos across the whole dendritic skeleton. Consequently, these dendrimers with multipurpose characters are the pinnacle of precision polymers and thereof are highly attractive to the scientific community as they can find use in a great number of cutting-edge applications, especially as discrete unimolecular carriers for therapeutic exploitation. Unfortunately, most established dendrimer families display external functionalities but lack internal scaffolding ability, which leads to inherent limitations to their full potential use as precision carriers. Consequently, here, we embark on a novel synthetic strategy facilitating the introduction of internal functionalization of established dendrimers. As a proof of concept, a new class of internally and externally functionalized multipurpose dendrimers based on the established 2,2-bis(methylol)propionic acid (bis-MPA) was successfully obtained by the elegant and simple design of AB2C monomers, amalgamated from two traditional AB2 monomers. Utilizing fluoride-promoted esterification (FPE), straightforward layer-by-layer divergent growth up to the fourth generation was successful in less than one day of reaction time, with a molecular weight of 15 kDa, and displaying 93 reactive groups divided by 45 internal and 48 external functionalities. The feasibility of postfunctionalization through click reactions is demonstrated, where the fast and effective attachment of drugs, dyes, and PEG chains is achieved, as well as cross-linking into multifunctional hydrogels. The simplicity and versatility of the presented strategy can easily be transferred to generate a myriad of functional materials such as polymers, surfaces, nanoparticles, or biomolecules.

Small-Molecule-Functionalized Hyperbranched Polyglycerol Dendrimers for Inhibiting Protein Aggregation.

Amyloid protein aggregation is responsible for a variety of neurodegenerative diseases, and antiamyloidogenic small molecules are identified for inhibiting such protein aggregation at extra-/intracellular space. We show that the nanoparticle form of small molecules offers better antiamyloidogenic performance via enhanced bioavailability and multivalent binding with protein. Here, we report hyperbranched polyglycerol dendrimers terminated with antiamyloidogenic small molecules such as gallate, tyrosine, and trehalose and their potential in inhibiting lysozyme/huntingtin protein aggregation under intra-/extracellular space. The synthesized functional dendrimers are ∼5 nm in size having an average molecular weight of ∼2000 Da, and they are highly biocompatible in nature. We found that functional dendrimers are efficient in micromolar doses with respect to molecular forms that are effective at millimolar concentration. It is observed that the trehalose-terminated dendrimer is more effective in inhibiting protein aggregation, whereas the gallate-terminated dendrimer is more effective in disintegrating mature protein fibrils. This approach can be used to design functional dendrimers as potential nanodrugs for the treatment of various neurodegenerative diseases.

Ferrocenyl Phosphorhydrazone Dendrimers Synthesis, and Electrochemical and Catalytic Properties.

The discovery of ferrocene is often associated with the rapid growth of organometallic chemistry. Dendrimers are highly branched macromolecules that can be functionalized at will at all levels of their structure. The functionalization of dendrimers with ferrocene derivatives can be carried out easily as terminal functions on the surface, but also at the core, or at one or several layers inside the structure. This review will focus on phosphorhydrazone dendrimers functionalized with ferrocene derivatives, on the surface, at the core, at all layers or within a single layer inside the structure. The first part will describe the synthesis; the second part will concern the electrochemical properties; and the last part will give several examples concerning catalysis, with complexes of ferrocenyl phosphines used as terminal functions of dendrimers.

Hierarchical integration of degradable mesoporous silica nanoreservoirs and supramolecular dendrimer complex as a general-purpose tumor-targeted biomimetic nanoplatform for gene/small-molecule anticancer drug co-delivery.

Biomacromolecule therapeutic systems are intrinsically susceptible to degradation and denaturation. Nanoformulations are promising delivery vehicles for therapeutic biomacromolecules (antibodies, genes and so on). However, their applications in these areas still face many challenges including in vivo stability, premature leakage and accurate tumor recognition. In this study, a generally applicable new strategy for tumor-targeted delivery of biomacromolecules was developed through the hierarchical integration of degradable large-pore dendritic mesoporous silica nanoparticles (dMSNs) and cyclodextrin-modified polyamidoamine (PAMAM-CD) dendrimers. The orifice rim of the dMSNs was modified with ROS-responsive nitrophenyl-benzyl-carbonate (NBC) groups while disulfide-bonded azido ligands were subsequently grafted onto the inner channel walls via heterogeneous functionalization. The PAMAM-CD was then interred into the dendritic pores via click reactions and supramolecularly loaded with archetypal hydrophobic small-molecule anticancer model drug (SN-38) and therapeutic model gene (Bcl-2 siRNA), after which dMSNs were eventually coated with a 4T1 cancer cell membrane (CCM). Experimental evidence demonstrated that the synthesized nanocarriers could efficiently deliver therapeutic cargos to target cancer cells and release them in the tumor cytosol in a cascade-responsive manner. This biomimetic nanoplatform presents a novel strategy to efficiently deliver biomolecular therapeutics in a tumor-targeted manner.

Functionalization of PAMAM dendrimers with curcumin: Synthesis, characterization, fluorescent improvement and application on PET polymer

Environmentally friendly and healthier demands of people lead to grow the application of the natural dyes, although some difficulties limit their usages. This means that overcoming these issues will suggest the exchange of synthetic dyes having many environmental problems with natural dyes. In the current study, to develop the natural dyes, we have enhanced the fluorescence intensity of yellow-emitting curcumin dye, by its covalently bonding to PAMAM dendrimer from G0, G1, G2 generations. The chemical structures of modified materials have been confirmed by FTIR, 1HNMR, 13CNMR, UV–Vis, DSC and Elemental Analysis techniques. The synthesized compounds have been used for polyethylene terephthalate (PET) fabrics dyeing at high temperature to study their color characteristics. On the other hand, the spectral characteristics of dendrimers have been evaluated in organic solvents with different polarity. The influence of dendrimer generation on the fluorescence intensity and quantum yield has also been described. The results showed that the new dendrimers can be used for PET fabrics coloration.

Trismaleimide Dendrimers: Helix-to-Superhelix Supramolecular Transition Accompanied by White-Light Emission.

Reported here are unprecedented fluorescent superhelices composed of primary, supramolecular polymers of the opposite helical twist. A new class of functional dendrimers was synthesized by amino-ene click reactions, and they demonstrate an alternating OFF/ON fluorescence with generation growth. A peripherally alkyl-modified dendrimer displays helix-sense-selective supramolecular polymerization, which predominantly forms right-handed (or left-handed) helical supramolecular polymers in the solution containing chiral solvents. With increasing the concentration, these primary helical supramolecular polymers spontaneously twist around themselves in the opposite direction to form superhelical structures. Atomic force microscopy and circular dichroism measurements were used to directly observe the helix-to-superhelix transition occurring with a reversal in the helical direction. Exceptional white-light emission was observed during superhelix formation.

Trismaleimide Dendrimers: Helix‐to‐Superhelix Supramolecular Transition Accompanied by White‐Light Emission

AbstractReported here are unprecedented fluorescent superhelices composed of primary, supramolecular polymers of the opposite helical twist. A new class of functional dendrimers was synthesized by amino‐ene click reactions, and they demonstrate an alternating OFF/ON fluorescence with generation growth. A peripherally alkyl‐modified dendrimer displays helix‐sense‐selective supramolecular polymerization, which predominantly forms right‐handed (or left‐handed) helical supramolecular polymers in the solution containing chiral solvents. With increasing the concentration, these primary helical supramolecular polymers spontaneously twist around themselves in the opposite direction to form superhelical structures. Atomic force microscopy and circular dichroism measurements were used to directly observe the helix‐to‐superhelix transition occurring with a reversal in the helical direction. Exceptional white‐light emission was observed during superhelix formation.

Sandwich-type ferrocene-functionalized magnetic nanoparticles: synthesis, characterization, and the adsorption of Cr(VI)

In this paper, novel ferrocene functionalized sandwich-type core–shell structure magnetic nanocomposites (Fe3O4@SiO2–FC/COOH) are synthesized using the Fe3O4 as the core and the ferrocene and 5-Aminoisophthalic acid as the functional dendrimers. Taking advantage of high redox activity benefit of ferrocene, Fe3O4@SiO2–FC/COOH is fabricated to adsorb Cr(VI) and reduce it to nontoxic Cr(III) in aqueous solution. The structure and morphology of prepared magnetic adsorbent are characterized by FTIR, XRD, SEM, XPS, TEM, EDS, and TGA. Moreover, the effects of different factors (such as solution pH, adsorption time, adsorption temperature, adsorbent dosage etc.) on adsorption are evaluated. XPS analysis indicates that Cr(VI) is successfully reduced to nontoxic Cr(III) after adsorption by Fe3O4@SiO2–FC/COOH. The Fe3O4@SiO2–FC/COOH exhibits excellent removal efficiency with a maximum Cr(VI) adsorption of 228.395 mg g−1 at pH 2.0. In addition, the adsorption experimental results fit well with the Freundlich isotherm model and the pseudo-second-order kinetic model. Desorption experiment results demonstrate that the regenerated adsorption capacity can exceed more than 95% after five times adsorption–desorption cycles. Therefore, this work provides a promising approach for Cr(VI) removal from water solution.

Design, Synthesis, and Characterization of Fully Zwitterionic, Functionalized Dendrimers.

Dendrimers are interesting candidates for various applications because of the high level of control over their architecture, the presence of internal cavities, and the possibility for multivalent interactions. More specifically, zwitterionic dendrimers modified with an equal number of oppositely charged groups have found use in in vivo biomedical applications. However, the design and control over the synthesis of these dendrimers remains challenging, in particular with respect to achieving full modification of the dendrimer. In this work, we show the design and subsequent synthesis of dendrimers that are highly charged while having zero net charge, that is zwitterionic dendrimers that are potential candidates for biomedical applications. First, we designed and fully optimized the synthesis of charge-neutral carboxybetaine and sulfobetaine zwitterionic dendrimers. Following their synthesis, the various zwitterionic dendrimers were extensively characterized. In this study, we also report for the first time the use of X-ray photoelectron spectroscopy as an easy-to-use and quantitative tool for the compositional analysis of this type of macromolecules that can complement techniques such as nuclear magnetic resonance and gel permeation chromatography. Finally, we designed and synthesized zwitterionic dendrimers that contain a variable number of alkyne and azide groups that allow straightforward (bio)functionalization via click chemistry.

Synthesis and in Vitro Evaluation of Monodisperse Amino-Functional Polyester Dendrimers with Rapid Degradability and Antibacterial Properties

Amine functional polymers, especially cationically charged, are interesting biomacromolecules for several reasons, including easy cell membrane entrance, their ability to escape endosomes through the proton sponge effect, spontaneous complexation and delivery of drugs and siRNA, and simple functionalization in aqueous solutions. Dendrimers, a subclass of precision polymers, are monodisperse and exhibit a large and exact number of peripheral end groups in relation to their size and have shown promise in drug delivery, biomedical imaging and as antiviral agents. In this work, hydroxyl functional dendrimers of generation 1 to 5 based on 2,2-bis(methylol)propionic acid (bis-MPA) were modified to bear 6 to 96 peripheral amino groups through esterification reactions with beta-alanine. All dendrimers were isolated in high yields and with remarkable monodispersity. This was successfully accomplished utilizing the present advantages of fluoride-promoted esterification (FPE) with imidazole-activated monomers. Straightforward postfunctionalization was conducted on a second generation amino-functional dendrimer with tetraethylene glycol through NHS-amidation and carbonyl diimidazole (CDI) activation to full conversion with short reaction times. Fast biodegradation of the dendrimers through loss of peripheral beta-alanine groups was observed and generational- and dose-dependent cytotoxicity was evaluated with a set of cell lines. An increase in neurotoxicity compared to hydroxyl-functional dendrimers was shown in neuronal cells, however, the dendrimers were slightly less neurotoxic than commercially available poly(amidoamine) dendrimers (PAMAMs). Additionally, their effect on bacteria was evaluated and the second generation dendrimer was found unique inhibiting the growth of Escherichia coli at physiological conditions while being nontoxic toward human cells. Finally, these results cement a robust and sustainable synthetic route to amino-functional polyester dendrimers with interesting chemical and biological properties.

Janus second-order nonlinear optical dendrimers: their controllable molecular topology and corresponding largely enhanced performance.

A new type of Janus dendrimers, consisting of two different side dendrons with the dipole orientation of the second-order nonlinear optical (NLO) chromophore moieties partially in a non-centrosymmetric direction, was intelligently designed and synthesized in order to enhance the macroscopic NLO performance and break through the limitation of NLO efficiency in the current molecular topological structure of azo chromophore-based polymers. This kind of Janus dendritic structure was constructed by the combination of convergent and divergent methods, with the utilization of a powerful "click chemistry reaction". The obtained three dendrimers, D-13N, D-17N and D-21N, show very high NLO performance, especially the dramatically enhanced NLO coefficient of 299 pm V-1 for D-13N, which is the highest value ever reported for polymers containing a simple azo chromophore. The new dendrimers provide a clear structure-properties relationship between high NLO efficiency and the controllable molecular topology with the non-centrosymmetrical alignment of dipole orientation, thus opening up a new avenue for the further development of NLO dendrimers with high performance and more importantly providing some clues for the rational design of functional dendrimers with controllable molecular topology.

Being Two Is Better than Being One: A Facile Strategy to Fabricate Multicomponent Nanoparticles for Efficient Gene Delivery.

Multifunctionality is necessary in the design of efficient gene vectors due to the existence of multiple barriers during gene delivery. Traditional methods in the design of polyfunctional materials for this purpose are associated with sophisticated syntheses and high costs. Here, we proposed a facile coassembly approach to fabricate multicomponent nanoparticles for efficient gene delivery. The resulting particles contain different functional dendrimers and show favorable physicochemical characteristics. All the combinations in the fabrication of multicomponent nanoparticles show a synergistic effect in improving transfection efficacy. The prepared nanoparticles successfully address two or more barriers in the gene delivery process and show minimal toxicity on the transfected cells. The combination of high transfection efficacy and low cytotoxicity suggests that the prepared multicomponent nanoparticles as promising carriers in gene delivery.