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Using dendron chemistry, we developed stability-enhanced carboxylate surface-modified (negatively charged dendron) AuNPs (Au-NCD). Since the carboxylate surface of Au-NCD is optimal for complexation with cisplatin (Pt) moieties, we further synthesized Pt-loaded Au-NCD (Au-NCD/Pt) to serve as potential therapeutic anticancer agents. The size distribution, zeta potential, and surface plasmon resonance of both Au-NCDs and Au-NCD/Pt were characterized via dynamic light scattering, scanning transmission electron microscopy, and ultraviolet–visible spectrophotometry. Surface chemistry, Pt uptake, and Pt release were evaluated using inductively coupled plasma-mass spectrometry and X-ray photoelectron spectroscopy. Colloidal stability in physiological media over a wide pH range (1–13) and shelf-life stability (up to 6 months) were also assessed. Finally, the cytotoxicity of both Au-NCD and Au-NCD/Pt to Chinese hamster ovary cells (CHO K1; as a normal cell line) and to human lung epithelial cells (A549; as a cancer cell line) was evaluated. The results of these physicochemical and functional cytotoxicity studies with Au-NCD/Pt demonstrated that the particles exhibited superlative colloidal stability, cisplatin uptake, and in vitro anticancer activity despite low amounts of Pt release from the conjugate. [ABSTRACT FROM AUTHOR]

Dendronized nanoparticles, also called nanoparticle-cored dendrimers, combine the advantages of nanoparticles and dendrimers. These very stable and polyvalent nanoparticles can be used for diverse applications. One such application is drug delivery, because the dendrons can enhance the density of the payload. In this report, we describe the design of multifunctional gold nanoparticles (AuNPs) coated with poly(propylene imine) (PPI) dendrons that contain both prostate cancer active targeting and chemotherapeutic drugs. The PPI dendron is a good candidate for the design of drug delivery vehicles because of its ability to induce a proton sponge effect that will enhance lysosomal escape and intracellular therapeutic delivery. The chemotherapeutic drug used is doxorubicin (DOX), and it was linked to the dendron through a hydrazone acid-sensitive bond. Subsequent acidification of the AuNP system to a pH of 4–5 resulted in the release of 140 DOX drugs per nanoparticles. In addition, the PPI dendron was conjugated via "click" chemistry to an EphA2-targeting antibody fragment that has been shown to target prostate cancer cells. In vitro cell viability assays revealed an IC50 of 0.9 nM for the targeted DOX-bearing AuNPs after 48 h incubation with PC3 cells. These results are very promising upon optimization of the system. [ABSTRACT FROM AUTHOR]

Dendrimers, being highly branched monodispersed macromolecules, predominantly exhibit identical terminal functionalities within their structural framework. Nonetheless, there are instances where the presence of two distinct surface functionalities becomes advantageous for the fulfilment of specific properties. To achieve this objective, one approach involves implementing Janus dendrimers, consisting of two dendrimeric wedges terminated by dissimilar functionalities. The prevalent method for creating these structures involves the synthesis of dendrons that possess a core functionality that complements that of a second dendron, facilitating their coupling to generate the desired dendrimers. In this comprehensive review, various techniques employed in the fabrication of phosphorus-based Janus dendrimers are elucidated, displaying the different coupling methodologies employed between the two units. The advantages of phosphorus dendrimers over classic dendrimers will be shown, as the presence of at least one phosphorus atom in each generation allows for the easy monitoring of reactions and the confirmation of purity through a simple technique such as 31P NMR, as these structures typically exhibit easily interpretable patterns. [ABSTRACT FROM AUTHOR]

COST Action CA17140 Cancer Nanomedicine—from the bench to the bedside (Nano2Clinic,) is the first, pan-European interdisciplinary network of representatives from academic institutions and small and medium enterprises including clinical research organizations (CROs) devoted to the development of nanosystems carrying anticancer drugs from their initial design, preclinical testing of efficacy, pharmacokinetics and toxicity to the preparation of detailed protocols needed for the first phase of their clinical studies. By promoting scientific exchanges, technological implementation, and innovative solutions, the action aims at providing a timely instrument to rationalize and focus research efforts at the European level in dealing with the grand challenge of nanomedicine translation in cancer, one of the major and societal-burdening human pathologies. Within CA17140, dendrimers in all their forms (from covalent to self-assembling dendrons) play a vital role as powerful nanotheranostic agents in oncology; therefore, the purpose of this review work is to gather and summarize the major results in the field stemming from collaborative efforts in the framework of the European Nano2Clinic COST Action. [ABSTRACT FROM AUTHOR]

All activities of our daily life, of the nature surrounding us and of the entire society and its complex economic and political systems are affected by stimuli. Therefore, understanding stimuli-responsive principles in nature, biology, society, and in complex synthetic systems is fundamental to natural and life sciences. This invited Perspective attempts to organize, to the best of our knowledge, for the first time the stimuli-responsive principles of supramolecular organizations emerging from self-assembling and self-organizable dendrons, dendrimers, and dendronized polymers. Definitions of stimulus and stimuli from different fields of science are first discussed. Subsequently, we decided that supramolecular organizations of self-assembling and self-organizable dendrons, dendrimers, and dendronized polymers may fit best in the definition of stimuli from biology. After a brief historical introduction to the discovery and development of conventional and self-assembling and self-organizable dendrons, dendrimers, and dendronized polymers, a classification of stimuli-responsible principles as internal- and external-stimuli was made. Due to the enormous amount of literature on conventional dendrons, dendrimers, and dendronized polymers as well as on their self-assembling and self-organizable systems we decided to discuss stimuli-responsive principles only with examples from our laboratory. We apologize to all contributors to dendrimers and to the readers of this Perspective for this space-limited decision. Even after this decision, restrictions to a limited number of examples were required. In spite of this, we expect that this Perspective will provide a new way of thinking about stimuli in all fields of self-organized complex soft matter. [ABSTRACT FROM AUTHOR]

Biorthogonal labelling with fluorescent small molecules is an indispensable tool for diagnostic and biomedical applications. In dye‐based 5‐ethynyl‐2′‐deoxyuridine (EdU) cell proliferation assays, augmentation of the fluorescent signal entails an overall enhancement in the sensitivity and quality of the method. To this end, a rapid, divergent synthetic procedure that provides ready‐to‐click pH‐insensitive rhodamine dyes exhibiting outstanding brightness was established. Compared to the shortest available synthesis of related high quantum‐yielding rhodamines, two fewer synthetic steps are required. In a head‐to‐head imaging comparison involving copper(I)‐catalyzed azide alkyne cycloaddition reactions with in vitro administered EdU, our new 3,3‐difluoroazetidine rhodamine azide outperformed the popular 5‐TAMRA‐azide, making it among the best available choices when it comes to fluorescent imaging of DNA. In a further exploration of the fluorescence properties of these dyes, a set of bis‐MPA dendrons carrying multiple fluorescein or rhodamine units was prepared by branching click chemistry. Fluorescence self‐quenching of fluorescein‐ and rhodamine‐functionalized dendrons limited the suitability of the dyes as labels in EdU‐based experiments but provided new insights into these effects. [ABSTRACT FROM AUTHOR]

The synthesis of a non‐steroidal anti‐inflammatory dendritic drug carrier, naproxen and ibuprofen‐based poly‐ester Janus dendrimer was carried out using a conventional azide‐alkyne click‐chemistry reaction. The corresponding dendron linkers contain naproxen and ibuprofen drug moieties on the surface and a stable [1,2,3]‐triazole as focal nucleus. The Janus dendrimer conjugate with four naproxen in one face and four ibuprofen on the other face was very active against human chronic myelogenous leukemia (K‐562) and human colorectal adenocarcinoma (HCT‐15) cells compared with cisplatin. This design provided an effective pathway for the synthesis of multiple drug carriers with two or more different end drugs in the structure. [ABSTRACT FROM AUTHOR]

Krzysztof Sztandera,1 Michał Gorzkiewicz,1,2 Mateusz Bątal,1 Valeria Arkhipova,3,4 Nadezhda Knauer,3,5,6 Javier Sánchez-Nieves,7,8 Fco Javier de la Mata,7– 9 Rafael Gómez,7– 9 Evgeny Apartsin,3,4,10 Barbara Klajnert-Maculewicz1 1Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, 90-236, Poland; 2Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, 40225, Germany; 3Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, 630090, Russia; 4Department of Natural Sciences, Novosibirsk State University, Novosibirsk, 630090, Russia; 5Research Institute of Fundamental and Clinical Immunology, Novosibirsk, 630099, Russia; 6Clinic for Neurosurgery, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, 40225, Germany; 7Departamento de Química Orgánica y Química Inorgánica, UAH-IQAR, Alcalá de Henares, 28805, Spain; 8Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, 28029, Spain; 9Instituto Ramón y Cajal de Investigación Sanitaria, IRYCIS, Madrid, 28034, Spain; 10Laboratoire de Chimie de Coordination CNRS, Toulouse, 31077, FranceCorrespondence: Barbara Klajnert-Maculewicz, Department of General Biophysics, Pomorska 141/143, Łódź, 90-236, Poland, Tel +48 42 635 44 29, Fax +48 42 635 4474, Email barbara.klajnert@biol.uni.lodz.plBackground: 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.Methods: 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).Results: Encapsulation of rose bengal inside dendrimersomes enhances cellular uptake, intracellular ROS production and concequently, the phototoxicity of this photosensitizer.Conclusion: Triazine-carbosilane dendrimersomes show high capacity as drug carriers for anticancer photodynamic therapy.Graphical Abstract: Keywords: dendrons, amphiphiles, carbosilane, photodynamic therapy, rose bengal, dendrimersomes

Nanomechanical properties and, in particular, the bending rigidity of natural and artifficial nanomembranes can be strongly affected by anchored or tethered macromolecules. We present the theory of the induced bending rigidity of polymer brushes symmetrically tethered to both surfaces of the membrane and immersed into the solvent. In contrast to previous works the finite thickness of the membrane was taken into account. The analytical and numerical variants of the self-consistent field approach were used. The mean and Gaussian Helfrich's bending moduli as functions of the polymerization degree, branching parameter and grafting density of tethered macromolecules were determined both for good and theta solvent conditions. It was shown that the absolute values of the Helfrich's bending moduli increase with the membrane thickness. The increase of the thickness leads also to the change of the relation between moduli for branched and linear brushes at the same polymerization degree and grafting density. For thin membranes the bending moduli for brushes with linear chains exceed those for branched brushes. However by an increase of the «bare» membrane thickness the moduli for brushes with branched macromolecules can become equal and even exceed those for brushes consisting of their linear analogs. [ABSTRACT FROM AUTHOR]

The construction of well-defined polyurethane dendrimers is challenging due to the high reactivity of externally added or in situ formed isocyanates leading to the formation of side products. With a primary focus of dendrimer research being the interaction of the periphery and the core, we report the synthesis of a common polyurethane dendron, which allows for the late-stage variation of both the periphery and the core. The periphery can be varied simply by installing a clickable unit in the dendron and then attaching to the core and vice-versa. Thus, a common dendron allows for varying periphery and core in the final two steps. To accomplish this, a protecting group-free, one-pot multicomponent Curtius reaction was utilized to afford a robust and versatile AB2 type polyurethane dendron employing commercially available simple molecules: 5-hydroxyisophthalic acid, 11-bromoundecanol, and 4-penten-1-ol. Subsequent late-stage modifications of either dendrons or dendrimers via a thiol-ene click reaction gave surface-functionalized alternating aromatic-aliphatic polyurethane homodendrimers to generation-three (G3). The dendrons and the dendrimers were characterized by NMR, mass spectrometry, and FT-IR analysis. A bifunctional AB2 type dendritic monomer demonstrated this approach’s versatility that can either undergo a thiol-ene click or attachment to the core. This approach enables the incorporation of functionalities at the periphery and the core that may not withstand the dendrimer growth for the synthesis of polyurethane dendrimers and other dendritic macromolecules.

Dendronized nanoparticles, also called nanoparticle-cored dendrimers, combine the advantages of nanoparticles and dendrimers. These very stable and polyvalent nanoparticles can be used for diverse applications. One such application is drug delivery, because the dendrons can enhance the density of the payload. In this report, we describe the design of multifunctional gold nanoparticles (AuNPs) coated with poly(propylene imine) (PPI) dendrons that contain both prostate cancer active targeting and chemotherapeutic drugs. The PPI dendron is a good candidate for the design of drug delivery vehicles because of its ability to induce a proton sponge effect that will enhance lysosomal escape and intracellular therapeutic delivery. The chemotherapeutic drug used is doxorubicin (DOX), and it was linked to the dendron through a hydrazone acid-sensitive bond. Subsequent acidification of the AuNP system to a pH of 4–5 resulted in the release of 140 DOX drugs per nanoparticles. In addition, the PPI dendron was conjugated via “click” chemistry to an EphA2-targeting antibody fragment that has been shown to target prostate cancer cells. In vitro cell viability assays revealed an IC50 of 0.9 nM for the targeted DOX-bearing AuNPs after 48 h incubation with PC3 cells. These results are very promising upon optimization of the system.

Dendrimers, being highly branched monodispersed macromolecules, predominantly exhibit identical terminal functionalities within their structural framework. Nonetheless, there are instances where the presence of two distinct surface functionalities becomes advantageous for the fulfilment of specific properties. To achieve this objective, one approach involves implementing Janus dendrimers, consisting of two dendrimeric wedges terminated by dissimilar functionalities. The prevalent method for creating these structures involves the synthesis of dendrons that possess a core functionality that complements that of a second dendron, facilitating their coupling to generate the desired dendrimers. In this comprehensive review, various techniques employed in the fabrication of phosphorus-based Janus dendrimers are elucidated, displaying the different coupling methodologies employed between the two units. The advantages of phosphorus dendrimers over classic dendrimers will be shown, as the presence of at least one phosphorus atom in each generation allows for the easy monitoring of reactions and the confirmation of purity through a simple technique such as 31P NMR, as these structures typically exhibit easily interpretable patterns.

COST Action CA17140 Cancer Nanomedicine—from the bench to the bedside (Nano2Clinic,) is the first, pan-European interdisciplinary network of representatives from academic institutions and small and medium enterprises including clinical research organizations (CROs) devoted to the development of nanosystems carrying anticancer drugs from their initial design, preclinical testing of efficacy, pharmacokinetics and toxicity to the preparation of detailed protocols needed for the first phase of their clinical studies. By promoting scientific exchanges, technological implementation, and innovative solutions, the action aims at providing a timely instrument to rationalize and focus research efforts at the European level in dealing with the grand challenge of nanomedicine translation in cancer, one of the major and societal-burdening human pathologies. Within CA17140, dendrimers in all their forms (from covalent to self-assembling dendrons) play a vital role as powerful nanotheranostic agents in oncology; therefore, the purpose of this review work is to gather and summarize the major results in the field stemming from collaborative efforts in the framework of the European Nano2Clinic COST Action.

Dendronized gold nanoparticles (AuNPs) were synthesized bearing charged peripheral groups. Two novel AB3-type dendrons were synthesized with a thiol group at the focal point followed by their attachment to AuNPs. Dendrons were designed to have nine charged peripheral groups (carboxyl or amine), glycol solubilizing, units and one thiol moiety at the focal point. Both dendrons and all intermediates were synthesized in high yields and characterized by nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). The amine- and carboxyl-terminated dendrons were used to functionalize gold nanoparticles (AuNPs) previously stabilized with citrate. The nanoparticles' diameters and their colloidal stability were investigated using dynamic light scattering (DLS). The size and morphology of the dendronized AuNPs were evaluated by scanning electron microscopy (SEM), which revealed individual particles with no aggregation after replacement of citrate by the dendrons, in agreement with the DLS data. The absorption spectroscopy reveals a prominent plasmonic band at 560 nm for all AuNPs. The zeta potential further confirmed the expected charged structures of the dendronized AuNPs. Considering all the physical–chemical properties of the charged dendronized AuNPs developed in this work, these AuNPs might be used as a weapon against multi-drug resistant bacterial infections. [ABSTRACT FROM AUTHOR]

High conductivity is critical for the practical applications of anion exchange membranes (AEMs) in fuel cells. In this study, a new strategy for enhanced conductivity and dimensional stability of AEMs by incorporating quaternized dendrons is proposed. Thanks to the introduced quaternized dendrons, distinct nanoscale phase separation and well‐connected ion conductive channels are formed in the as‐prepared membranes (PPO‐QG‐x). As a result, PPO‐QG‐x AEMs achieve high hydroxide conductivities up to 65.5 mS cm−1 at 20 °C and 121.5 mS cm−1 at 80 °C (IEC = 1.95 mmol g−1), while possessing good dimensional stability. Meanwhile, PPO‐QG‐x AEMs show good alkaline stability with the maximum loss in conductivity of 15.1% after treated in 2 M NaOH at 80 °C for 960 h. In addition, the single‐cell assembled with PPO‐QG‐12 membrane exhibit a peak power density of 249.4 mW cm−2 at 60 °C. Overall, this work provides a new insight to achieve high conductivity of AEMs. [ABSTRACT FROM AUTHOR]

The rational design of perfluorinated amphiphiles to control the supramolecular aggregation in an aqueous medium is still a key challenge for the engineering of supramolecular architectures. Here, the synthesis and physical properties of six novel non‐ionic amphiphiles are presented. The effect of mixed alkylated and perfluorinated segments in a single amphiphile is also studied and compared with only alkylated and perfluorinated units. To explore their morphological behavior in an aqueous medium, dynamic light scattering (DLS) and cryogenic transmission electron microscopy/electron microscopy (cryo‐TEM/EM) measurements are used. The assembly mechanisms with theoretical investigations are further confirmed, using the Martini model to perform large‐scale coarse‐grained molecular dynamics simulations. These novel synthesized amphiphiles offer a greater and more systematic understanding of how perfluorinated systems assemble in an aqueous medium and suggest new directions for rational designing of new amphiphilic systems and interpreting their assembly process. [ABSTRACT FROM AUTHOR]

The construction of well-defined polyurethane dendrimers is challenging due to the high reactivity of externally added or in situ formed isocyanates leading to the formation of side products. With a primary focus of dendrimer research being the interaction of the periphery and the core, we report the synthesis of a common polyurethane dendron, which allows for the late-stage variation of both the periphery and the core. The periphery can be varied simply by installing a clickable unit in the dendron and then attaching to the core and vice-versa. Thus, a common dendron allows for varying periphery and core in the final two steps. To accomplish this, a protecting group-free, one-pot multicomponent Curtius reaction was utilized to afford a robust and versatile AB2 type polyurethane dendron employing commercially available simple molecules: 5-hydroxyisophthalic acid, 11-bromoundecanol, and 4-penten-1-ol. Subsequent late-stage modifications of either dendrons or dendrimers via a thiol-ene click reaction gave surface-functionalized alternating aromatic-aliphatic polyurethane homodendrimers to generation-three (G3). The dendrons and the dendrimers were characterized by NMR, mass spectrometry, and FT-IR analysis. A bifunctional AB2 type dendritic monomer demonstrated this approach's versatility that can either undergo a thiol-ene click or attachment to the core. This approach enables the incorporation of functionalities at the periphery and the core that may not withstand the dendrimer growth for the synthesis of polyurethane dendrimers and other dendritic macromolecules. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Dendronized gold nanoparticles (AuNPs) were synthesized bearing charged peripheral groups. Two novel AB3-type dendrons were synthesized with a thiol group at the focal point followed by their attachment to AuNPs. Dendrons were designed to have nine charged peripheral groups (carboxyl or amine), glycol solubilizing, units and one thiol moiety at the focal point. Both dendrons and all intermediates were synthesized in high yields and characterized by nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). The amine- and carboxyl-terminated dendrons were used to functionalize gold nanoparticles (AuNPs) previously stabilized with citrate. The nanoparticles’ diameters and their colloidal stability were investigated using dynamic light scattering (DLS). The size and morphology of the dendronized AuNPs were evaluated by scanning electron microscopy (SEM), which revealed individual particles with no aggregation after replacement of citrate by the dendrons, in agreement with the DLS data. The absorption spectroscopy reveals a prominent plasmonic band at 560 nm for all AuNPs. The zeta potential further confirmed the expected charged structures of the dendronized AuNPs. Considering all the physical–chemical properties of the charged dendronized AuNPs developed in this work, these AuNPs might be used as a weapon against multi-drug resistant bacterial infections.

Nanomedicine represents a very significant contribution in current cancer treatment; in addition to surgical intervention, radiation and chemotherapeutic agents that unfortunately also kill healthy cells, inducing highly deleterious and often life-threatening side effects in the patient. Of the numerous nanoparticles used against cancer, gold nanoparticles had been developed for therapeutic applications. Inter alia , a large variety of dendrimers, i.e. soft artificial macromolecules, have turned up as non-viral functional nanocarriers for entrapping drugs, imaging agents, and targeting molecules. This review will provide insights into the design, synthesis, functionalization, and development in biomedicine of engineered functionalized hybrid dendrimer-tangled gold nanoparticles in the domain of cancer theranostic. Several aspects are highlighted and discussed such as 1) dendrimer-entrapped gold(0) hybrid nanoparticles for the targeted imaging and treatment of cancer cells, 2) dendrimer encapsulating gold(0) nanoparticles (Au DENPs) for the delivery of genes, 3) Au DENPs for drug delivery applications, 4) dendrimer encapsulating gold radioactive nanoparticles for radiotherapy, and 5) dendrimer/dendron-complexed gold(III) nanoparticles as technologies to take down cancer cells. [Display omitted] • Extraordinary growing interest of nanotechnology in medicine. • Dendrimer/dendron-entrapped/complexed gold(0)/(III) nanoparticles to tackle cancers. • Dendrimer encapsulating gold(0) nanoparticles for gene and drug delivery. • Gold nanoparticles as theranostics nanoplatforms in cancer therapy. • Dendrimer-entrapped gold radioactive nanoparticles for radiotherapy. [ABSTRACT FROM AUTHOR]

Dendrons are an important class of macromolecules that can be used for a broad range of applications. Recent studies have indicated that mixtures of oligoglycerol detergent (OGD) regioisomers are superior to individual regioisomers for protein extraction. The origin of this phenomenon remains puzzling. Here we discuss the synthesis and characterization of dendritic oligoglycerol regioisomer mixtures and their implementation into detergents. We provide experimental benchmarks to support quality control after synthesis and investigate the unusual utility of OGD regioisomer mixtures for extracting large protein quantities from biological membranes. We anticipate that our findings will enable the development of mixed detergent platforms in the future. [ABSTRACT FROM AUTHOR]

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.

In the current era, the dendrimers have vast potential applications in the area of electronics, healthcare, pharmaceuticals, biotechnology, engineering products, photonics, drug delivery, catalysis, electronic devices, nanotechnologies and environmental issues. This review recaps the synthesis, characterization and applications of poly-aliphatic amine dendrimers. [ABSTRACT FROM AUTHOR]

Specifically amplifying the emission signals of optical probes in tumors is an effective way to improve the tumor‐imaging sensitivity and contrast. In this paper, the first case of dendron‐based fluorescence turn‐on probes mediated by a Förster resonance energy transfer (FRET) mechanism is reported. Dendrons up to the fourth generation with a hydrophilic oligo(ethylene glycol) scaffold are synthesized by a solid‐phase synthesis strategy, and show precise and defect‐free chemical structures. To construct the fluorescence turn‐on probe, one Cy5.5 molecule is conjugated to the focal of a G3 dendron through a robust linkage and eight Black Hole Quencher 3 (BHQ‐3) molecules are conjugated to its periphery through a PEG chain bearing a reductively cleavable disulfide linkage. By in vitro and in vivo experiments, it is demonstrated that the fluorescence of the dendron‐based probe can be activated effectively and rapidly in the reductive environments of tumor cells and tissues, and the probe thus exhibits amplified tumor signals and weak normal tissue signals. Compared with the reported nanoscale turn‐on probes, the dendron‐based probe has several significant advantages, such as well‐defined chemical structure, precisely controllable fluorophore/quencher conjugation sites and ratio, desirable chemical stability, and reproducible pharmacokinetic and pharmacological profiles, and is very promising in tumor detection. [ABSTRACT FROM AUTHOR]

First‐in‐class CuII and AuIII metaled phosphorus dendrons were synthesized and showed significant antiproliferative activity against several aggressive breast cancer cell lines. The data suggest that the cytotoxicity increases with reducing length of the alkyl chains, whereas the replacement of CuII with AuIII considerably increases the antiproliferative activity of metaled phosphorus dendrons. Very interestingly, we found that the cell death pathway is related to the nature of the metal complexed by the plain dendrons. CuII metaled dendrons showed a potent caspase‐independent cell death pathway, whereas AuIII metaled dendrons displayed a caspase‐dependent apoptotic pathway. The complexation of plain dendrons with AuIII increased the cellular lethality versus dendrons with CuII and promoted the translocation of Bax into the mitochondria and the release of Cytochrome C (Cyto C). [ABSTRACT FROM AUTHOR]

The synthesis of long‐chain, aliphatic and space filling dendritic ligands containing (pro)mesogenic, aliphatic or nitrile biphenyl moieties for the stabilization of magnetic nanoparticles in liquid crystal hosts is described. A Negishi or Sonogashira cross‐coupling is exploited as a key step in the synthetic sequence. These synthetic procedures enable the synthesis of various ligands which can be easily adapted to different types of liquid crystals [e.g. 4‐pentyl‐4′‐cyanobiphenyl (5CB)]. For instance, a three‐step sequence (i.e. etherfication, Sonogashira–Hagihara cross‐coupling and Steglich‐esterfication) yields a dendritic ligand in 77 % overall yield starting from literature known compounds. The length of the ligand is important to stabilize the magnetic nanoparticles, and, therefore, the length of the ligand may be easily modified by this approach. Indeed, the established synthesis can readily tackle this issue. [ABSTRACT FROM AUTHOR]

A series of polyester dendrimers (1G to 3G generation) based on 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoic acid (bis-MPA) and the core of 1,3-propanediol-2-(hydroxymethyl)-2-methyl (TME) were synthesized and conjugated to the α,β-dipeptide (N-Cbz-Phe-N-Bn-β-Ala-COOH) in convergent fashion. Conventional esterification (DCC, DMAP, DPTS) was used for the above coupling, followed by removal of protecting groups (acetonide and Cbz groups) to provide seven novel organocatalysts exhibiting different sizes and solubilities. The dendritic nature (mono- or di-substituted), ending groups (acetonide or hydroxyl groups) and generation effects of these organocatalysts were evaluated in the Michael addition reaction of isobutyraldehyde to N-phenylmaleimide as benchmark reaction, both in solution and under neat reaction conditions. Reaction yields when using 10 mol% of organocatalyst and NaOH as base varied in the range of good to excellent (neat 96%, aqueous solution 98%, CH2Cl2 solvent 80%), while enantioselectivity as high as 81:19 was achieved. The above enantioselectivity is in line with a positive "dendritic effect". Regarding the influence of terminal groups, it is appreciated that hydroxyl end-groups afford higher yield relative to analogous acetonide terminal groups. Finally, the scope of the reaction was evaluated with catalysts H2N-Phe-N-Bn-β-Ala-TME-d-2G-A and H2N-Phe-N-Bn-β-Ala-TME-d-2G-OH, which could be recovered and recycled for at least three times without significant loss of catalytic activity. [ABSTRACT FROM AUTHOR]

Abstract In this study, we have successfully synthesized a novel coumarin-based dendrons derivative CD and its chemical structure was characterized by 1H NMR, 13C NMR and ESI-HR-MS. The sensor CD showed an obvious "on-off" fluorescence quenching response toward Cu2+ with a maximum quenching efficiency of 99.8%. The CD -Cu2+ complex showed an "off-on" fluorescence enhancement response toward PPi over many competitive anions. The detection limit of the sensor CD was 0.29 × 10−6 M to Cu2+ and 2.39 × 10−9 M to PPi. In addition, the sensor CD showed a 1:1 binding stoichiometry to Cu2+ and the sensor CD -Cu2+ showed a 2:1 binding stoichiometry to PPi in CH 3 CN/HEPES buffer medium (9:1 v/v, pH = 7.2). The stable pH range of sensor CD to Cu2+ and CD -Cu2+ to PPi was from 3 to 8. Graphical abstract Image 1 Highlights • A novel coumarin-based containing denrons derivative CD was synthesized. • The sensor CD can be used to sequential detect Cu2+ and PPi in CH 3 CN/HEPES buffer medium. • The detection limits for Cu2+ and PPi were estimated to be 0.29 × 10−6 and 2.39 × 10−9 M, respectively. [ABSTRACT FROM AUTHOR]

Research of national specificity of phraseology in a national language by distinguishing thematic groups of phraseological units and the analysis of their component composition becomes increasingly important in linguistic studies. This article is devoted to the analysis of the French phraseological units, which include dendronyms. Authors narrow notion of “dendronym” and use it only to refer to the names of trees. In French phraseological corpus authors identified 18 dendronyms, which are core components of the floral phrasal units: amandier (almond tree), cèdre (cedar), chêne (oak), cocotier (coconut palm), cyprès (cypress), figuier (fig tree), laurier (laurel tree), mûrier (mulberry), olivier (olive tree), orme (elm), osier (willow), palmier (palm), peuplier (poplar), platane (sycamore), poirier (pear), pommier (apple), prunier (plum), sapin (spruce, fir). The following list proves that the repertoire of dendronyms used to form French FU is not too wide. However, the authors confirmed the possibility to consider idioms-dendronym component as special items of historical and cultural memory.

To the best of our knowledge, this is the very first time that a thorough study of the synthetic procedures, molecular and thermal characterization, followed by structure/properties relationship for symmetric and non-symmetric second generation (2-G) dendritic terpolymers is reported. Actually, the synthesis of the non-symmetric materials is reported for the first time in the literature. Anionic polymerization enables the synthesis of well-defined polymers that, despite the architecture complexity, absolute control over the average molecular weight, as well as block composition, is achieved. The dendritic type macromolecular architecture affects the microphase separation, because different morphologies are obtained, which do not exhibit long range order, and various defects or dislocations are evident attributed to the increased number of junction points of the final material despite the satisfactory thermal annealing at temperatures above the highest glass transition temperature of all blocks. For comparison reasons, the initial dendrons (miktoarm star terpolymer precursors) which are connected to each other in order to synthesize the final dendritic terpolymers are characterized in solution and in bulk and their self-assembly is also studied. A major conclusion is that specific structures are adopted which depend on the type of the core connection between the ligand and the active sites of the dendrons.

(1) Background: Natural peptides supporting the innate immune system studied at the functional and mechanistic level are a rich source of innovative compounds for application in human therapy. Increasing evidence indicates that apart from antimicrobial activity, some of them exhibit selective cytotoxicity towards tumor cells. Their cationic, amphipathic structure enables interactions with the negatively-charged membranes of microbial or malignant cells. It can be modeled in 3D by application of dendrimer chemistry. (2) Methods: Here we presented design principles, synthesis and bioactivity of branched peptides constructed from ornithine (Orn) assembled as proline (Pro)- or histidine (His)-rich dendrons and dendrimers of the bola structure. The impact of the structure and amphipathic properties of dendrons/dendrimers on two glioblastoma cell lines U87 and T98G was studied with the application of proliferation, apoptosis and cell migration assays. Cell morphology/cytoskeleton architecture was visualized by immunofluorescence microscopy. (3) Results: Dimerization of dendrons into bola dendrimers enhanced their bioactivity. Pro- and His-functionalized bola dendrimers displayed cytostatic activity, even though differences in the responsiveness of U87 and T98G cells to these compounds indicate that their bioactivity depends not only on multiple positive charge and amphipathic structure but also on cellular phenotype. (4) Conclusion: Ornithine dendrons/dendrimers represent a group of promising anti-tumor agents and the potential tools to study interrelations between drug bioactivity, its chemical properties and tumor cells’ phenotype.

The synthesis, characterization, and catalytic testing of copper and copper:gold nanoparticles in melamine-based dendrons supported on SBA-15 is reported. It was found that by first making small gold nanoparticles using the dendrons as templates, stable copper(0) overlayers could then be successfully deposited. These samples were used as catalysts for the click reaction, with the most active samples possessing rates of 8.9 mol triazole produced/(mol copper – hour), nearly 50 times high than literature reports of copper nanoparticles in solution. In contrast, the gold nanoparticles themselves are inert for this reaction, consistent with the copper being deposited as an overlayer on the gold nanoparticles. Copper leaching was shown to be less pronounced for particles formed in the dendrons versus copper simply deposited on SBA-15. Larger dendrons lead to suppressed rates due to diffusion resistance with rates decreasing from 8.9 to 5.2 to 0.69 mol triazole produced/(mole Cu-hour) for G1, G2, and G3 respectively. Infrared spectroscopy was used to monitor the reaction in real time, and provided information about the various surface intermediates formed. [ABSTRACT FROM AUTHOR]

In this paper, we describe the synthesis and characterization of four novel pyrene labeled compounds, some of them dendritic, which can act as potential sensors for the detection of nitro compounds in methanol solution. Methanol was selected as solvent due to its polar properties, which provide similar characteristics to water. The obtained pyrene labeled molecules (PyOH, Pytb, PyNK1OH and PyNK1tb) were studied by UV-Vis and steady state fluorescence spectroscopy. Their application as sensors has been tested with three different nitro compounds: nitrobenzene, 1-chloro-2,4-dinitrobenzene and nitromethane. PyOH and Pytb showed a detection concentration limit for the analyzed quenchers in the order of nM, making these compounds suitable for high-sensitive sensoring. PyNK1OH and PyNK1tb displayed high sensibility at µM concentration. All the sensors showed an accurate response towards quencher analytes. [ABSTRACT FROM AUTHOR]

The synthesis of new dendrons of the generations 0, 1 and 2 with a double bond at the focal point and a carbonyl group at the termini has been carried out. The carbonyl group has been exploited for the multivalent conjugation to a sample saccharide by reductive amination and alkoxyamine conjugation.

In this report, two new redox-responsive complexes with different dendritic tail chain number (P4VP- n Fc, n = 1, 2) were prepared via the hydrogen-bonded self-assembly of poly(4-vinylpyridine) and ferrocenyl-modified percec-type dendrons. These complexes exhibited a crystalline phase for P4VP-1Fc and liquid crystalline for P4VP-2Fc at room temperature. The cyclic voltammetry measurement shows that the electrode process of P4VP- n Fc ( n = 1, 2) films was diffusion controlled and the reversibility of the electrode process for the P4VP-2Fc films became better than that for the P4VP-1Fc. Moreover, the redox peak current | i p | increased with increasing dendritic tail chain number n in the complex, because the complex film formed with 2Fc-COOH has the looser stacking of alkyl chains, which was favorable for the electrolyte diffusion and charge transfer. The present results demonstrate that the electrochemical activity of the redox-responsive poly(4-vinylpyridine) -ferrocenyl dendron complex can be easily tuned using the dendritic tail chain with different numbers. These complexes may be used as new kinds of modified electrodes. [ABSTRACT FROM AUTHOR]

Dendrimers and dendrons offer an excellent platform for developing novel drug delivery systems and medicines. The rational design and further development of these repetitively branched systems are restricted by difficulties in scalable synthesis and structural determination, which can be overcome by judicious use of molecular modelling and molecular simulations. A major difficulty to utilise in silico studies to design dendrimers lies in the laborious generation of their structures. Current modelling tools utilise automated assembly of simpler dendrimers or the inefficient manual assembly of monomer precursors to generate more complicated dendrimer structures. Herein we describe two novel graphical user interface toolkits written in Python that provide an improved degree of automation for rapid assembly of dendrimers and generation of their 2D and 3D structures. Our first toolkit uses the RDkit library, SMILES nomenclature of monomers and SMARTS reaction nomenclature to generate SMILES and mol files of dendrimers without 3D coordinates. These files are used for simple graphical representations and storing their structures in databases. The second toolkit assembles complex topology dendrimers from monomers to construct 3D dendrimer structures to be used as starting points for simulation using existing and widely available software and force fields. Both tools were validated for ease-of-use to prototype dendrimer structure and the second toolkit was especially relevant for dendrimers of high complexity and size. [ABSTRACT FROM AUTHOR]

The challenges of medicine today include the increasing stipulation for sensitive and effective systems that can improve the pathological responses with a simultaneous reduction in accumulation and drug side effects. The demand can be fulfilled through the advancements in nanomedicine that includes nanostructures and nanodevices for diagnosing, treating, and prevention of various diseases. In this respect, the nanoscience provides various novel techniques with carriers such as micelles, dendrimers, particles and vesicles for the transportation of active moieties. Further, an efficient way to improve these systems is through stimuli a responsive system that utilizes supramolecular hyperbranched structures to meet the above criteria. The stimuli-responsive dendritic architectures exhibit spatial, temporal, convenient, effective, safety and controlled drug release in response to specific trigger through electrostatic interactions plus π stacking. The stimuli-responsive systems are capable of sequestering the drug molecules underneath a predefined set of conditions and discharge them in a different environment through either exogenous or endogenous stimulus. The incorporation of photoresponsive moieties at various components of dendrimer such as core, branches or at the peripheral end exaggerates its significance in various allied fields of nanotechnology which includes sensors, photoswitch, electronic widgets and in drug delivery systems. This is due to the light instigated geometrical modifications at the core or at the surface molecules which generates huge conformational changes throughout the hyperbranched structure. Further, numerous synthetic methodologies have been investigated for utilization of dendrimers in therapeutic drug delivery and its applicability towards stimuli responsive systems such as photo-instigated, thermal-instigated, and pH-instigated hyperbranched structures and their advancement in the field of nanomedicine. This paper highlights the fascinating theoretical advances and principal mechanisms of dendrimer synthesis and their ability to capture light that strengthens its applicability from radiant energy to medical photonics. [ABSTRACT FROM AUTHOR]

Polyurethanes grafted with well-defined polar pendants were synthesized and investigated. A series of linear and dendritic poly(urea/malonamide)s with uniform chain length were first prepared from an iterative synthesis route, which is based on a dual-functional building block, 4-isocyanate-4´-(3,3-dimethyl-2,4-dioxo-azetidine)diphenyl methane (IDD). Moreover, side chain polyurethanes (SPUs) bearing azetidine-2,4-dione functional groups were prepared from one pot reaction for following post-functionalization of poly(urea/malonamide)s when IDD-diols were added to polyurethane prepolymers as chain extenders. Subsequently, the azetidine-2,4-dione functional groups on the SPUs underwent addition reactions with amino functional group containing dendritic or linear poly(urea/malonamide)s under mild condition, without the need of catalyst and protection/deprotection procedure to achieve polyurethanes grafted with well-defined pendants. Mechanical properties of these comb-like polyurethanes strongly depend on the architecture and the molecular length of poly(urea/malonamide) pendants, which could be adjusted by the grafting fractions of the dendritic or linear poly(urea/malonamide)s with various generations. These poly(urea/malonamide) pendants provided strong hydrogen bonding interactions to achieve physical crosslinking effects in the polyurethanes. Consequently, the polyurethanes with improved mechanical properties and sustained phase transition exhibit shape memory properties. [ABSTRACT FROM AUTHOR]

Organic macromolecules with dendrimeric architectures are polymeric materials potentially useful as nanocarriers for therapeutic drugs. In this work, we evaluate a series of Newkome-type dendrons in Langmuir and Langmuir-Blodgett films as platforms capable of interacting with a potential antitumoral agent. The nanocomposite is proposed as model for the development of surface mediated drug delivery systems. We were successful in the formation and characterization of pure (dendrons) and composite (drug-dendron) stable and reproducible monolayers, and their transfer to solid substrates. A detailed study of topographic characteristics of the generated surfaces by atomic force microscopy was conducted. Furthermore, we probed dendron monolayer films as anchorage surfaces for mammalian cells. Normal cell attachment and proliferation on the surfaces were observed. No evident cytotoxic effects were detected, demonstrating the adequate biocompatibility of the surfaces. [ABSTRACT FROM AUTHOR]

The synthesis of novel bifunctional organosilicon dendrons has been successfully achieved. The synthetic route is based on sequential platinum-catalyzed hydrosilylation reactions, that efficiently leads to the corresponding carbosilane dendrons containing a wide range of functional groups, such as –OSiMe 3 , –Cl, –F and –COOCR. Finally, the core of these dendrons comprises reactive alkoxy groups that can be further used for grafting in various materials. [ABSTRACT FROM AUTHOR]

2,2-Bis(azidomethyl)propionic acid was prepared in four steps and 85% yield from the commercially available 2,2-bis(hydroxymethyl) propionic acid and used as the starting building block for the divergent, convergent, and double-stage convergent-divergent iterative methods for the synthesis of dendrimers and dendrons containing ethylenediamine (EDA), piperazine (PPZ), and methyl 2,2-bis(aminomethyl)propionate (COOMe) cores. These cores have the same multiplicity but different conformations. A diversity of synthetic methods were used for the synthesis of dendrimers and dendrons. Regardless of the method used, a self-interruption of the synthesis was observed at generation 4 for the dendrimer with an EDA core and at generation 5 for the one with a PPZ core, whereas for the COOMe core, self-interruption was observed at generation 6 dendron, which is equivalent to generation 5 dendrimer. Molecular modeling and molecular-dynamics simulations demonstrated that the observed self-interruption is determined by the backfolding of the azide groups at the periphery of the dendrimer. The latter conformation inhibits completely the heterogeneous hydrogenation of the azide groups catalyzed by 10% Pd/carbon as well as homogeneous hydrogenation by the Staudinger method. These self-terminated polyamide dendrimers are enzymatically and hydrolytically stable and also exhibit antimicrobial activity. Thus, these nanoscale constructs open avenues for biomedical applications. [ABSTRACT FROM AUTHOR]

The immense scope of variation in dendritic molecules (hyper-branching, nano-sized, hydrophobicity/hydrophilicity, rigidity/flexibility balance, etc.) and their versatile functionalization, with the possibility of multivalent binding, permit the design of highly improved, novel materials. Dendritic-based materials are therefore viable alternatives to conventional polymers. The overall aim of this work is to show the advantages of dendronization processes by presenting the synthesis and characterization of three different dendronized systems: (I) microbeads of functionalized chitosan; (II) nanostructuration of polypropylene surfaces; and (III) smart dendritic nanogels. The particular properties yielded by these systems could only be achieved thanks to the dendronization process. [ABSTRACT FROM AUTHOR]

Self-host thermally activated delayed fluorescence (TADF) materials have recently been identified as effective emitters for solution-processed nondoped organic light-emitting diodes (OLEDs). However, except for the carbazole unit, few novel dendrons have been developed to build self-host TADF emitters. This study reports two self-host blue materials, tbCz-SO and poCz-SO, with the same TADF emissive core and different dendrons. The influence of the peripheral dendrons on the photophysical properties and electroluminescent performances of the self-host materials were systematically investigated. The transient fluorescence and electroluminescence spectra indicated that the diphenylphosphoryl carbazole units could effectively encapsulate the emissive core to reduce the concentration quenching effect and to enhance reverse intersystem crossing. By using tbCz-SO and poCz-SO as host-free blue emitters, the performance of the solution-processed nondoped OLED device demonstrated that a more balanced charge transfer from the bipolar dendrons would offer a better current efficiency of 10.5 cd A−1 and stable color purity with Commission Internationale de L'Eclairage units of (0.18, 0.27). [ABSTRACT FROM AUTHOR]