Dendritic Polyamine Research Articles

Quantitative Luminescence Photography of a Swellable Hydrogel Dressing with a Traffic-Light Response to Oxygen.

Sensor-integrated wound dressings are emerging tools applicable to a wide variety of medical applications from emergency triage to at-home monitoring. Uncomfortable, unnecessary wound dressing changes may be avoided by providing quantitative insight into tissue characteristics related to wound healing such as tissue oxygenation, pH, and exudate/transudate volume. Here, a simple cost-effective methodology for quantifying oxygen and pH in a swellable hydrogel dressing using a single photograph is presented. The red and green luminescence of a novel dendritic polyamine Pt-porphyrin and fluorescein conjugate quantitatively responds to oxygen and pH, respectively, and enables robust sensing. The porphyrin conjugate, when combined with a four-arm star polyethylene glycol (PEG) amine polymer, rapidly crosslinks at room temperature with an N-hydroxysuccinimide (NHS)-PEG crosslinker to form a color-changing hydrogel dressing with tunable swelling capabilities applicable to a variety of wound environments. An inexpensive digital single-lens reflex (DSLR) camera modified with bandpass filters captures the hydrogel luminescence using simple macroscopic photography, and conversion to HSB colorspace allows for intensity-independent image analysis of the hydrogels' dual modality response. The hydrogel formulation exhibits a robust and validated visible red-orange-green "traffic light" spectrum in response to oxygen changes, regardless of swelling state, pH, or autofluorescence from skin, thereby enabling the clinician friendly naked-eyefeedback.

Highly efficient removal of Cu(ii) by novel dendritic polyamine-pyridine-grafted chitosan beads from complicated salty and acidic wastewaters.

In this study, dendritic polyamine chitosan beads with and without 2-aminomethyl pyridine were facilely prepared and characterized. Compared to CN (without the pyridine function), more adsorption active sites, larger pores, higher nitrogen content, higher specific surface area, and higher strength could be obtained for CNP (with the pyridine function). CNP microspheres afforded a larger adsorption capacity than those obtained by CN for different pH values; further, the uptake amounts of Cu(ii) were 0.84 and 1.12 mmol g−1 for CN and CNP beads, respectively, at pH 5. The CNP microspheres could scavenge Cu(ii) from highly acidic and salty solutions: the maximum simulated uptake amount of 1.93 mmol g−1 at pH 5 could be achieved. Due to the strong bonding ability and weakly basic property of pyridine groups, the adsorption capacity of Cu(ii) at pH 1 was 0.75 mmol g−1 in highly salty solutions, which was comparative to those obtained from the commercial pyridine chelating resin M4195 (QCu(II) = 0.78 mmol g−1 at pH 1). In addition, a distinct salt-promotion effect could be observed for CNP beads at both pH 5 and 1. Therefore, the prepared adsorbent CNP beads can have promising potential applications in the selective capturing of heavy metals in complex solutions with higher concentrations of H+ and inorganic salts, such as wastewaters from electroplating liquid and battery industries.

Effect of Superbasic Ionic Liquids on the Synthesis of Dendritic PolyaminesviaAza-Michael Addition Reaction

Catalytic effect of selected superbasic ionic liquids on the yield and selectivity of aza-Michael addition of ethylenediamine and ammonia to acrylonitrile was investigated. The reactions were performed in calorimetric reactor equipped with RT-IR probe (real-time IR), where all energy changes associated with chemical reactions and physical transformations were monitored. Catalytic activity of selected superbasic ionic liquids in aza-Michael addition ethylenediamine and ammonia to acrylonitrile were determined and obtained polynitriles were then hydrogenatated to final three- and four-directional dendritic polyamines. The products were characterized by instrumental analytical methods, including 1H-NMR, GC/MS, FTIR and DSC. Application of superbasic ionic liquids positively influenced both the yield of aza-Michael addition and selectivity to fully branched products.

ChemInform Abstract: Dendritic Glycopolymers Based on Dendritic Polyamine Scaffolds: View on Their Synthetic Approaches, Characteristics and Potential for Biomedical Applications

AbstractReview: 274 refs.

Dendritic glycopolymers based on dendritic polyamine scaffolds: view on their synthetic approaches, characteristics and potential for biomedical applications.

In this review we highlight the potential for biomedical applications of dendritic glycopolymers based on polyamine scaffolds. The complex interplay of the molecular characteristics of the dendritic architectures and their specific interactions with various (bio)molecules are elucidated with various examples. A special role of the individual sugar units attached to the dendritic scaffolds and their density is identified, which govern ionic and H-bond interactions, and biological targeting, but to a large extent are also responsible for the significantly reduced toxicity of the dendritic glycopolymers compared to their polyamine scaffolds. Thus, the application of dendritic glycopolymers in drug delivery systems for gene transfection but also as therapeutics in neurodegenerative diseases has great promise.

Oligosaccharide shells as a decisive factor for moderate and strong ionic interactions of dendritic poly(ethylene imine) scaffolds under shear forces.

For better understanding and improving the non-covalent interactions of dendritic core-shell, we evaluated the interactions of hyperbranched poly(ethylene imine) (PEI) decorated with various oligosaccharide shells with water-soluble B vitamins, an estradiol derivative and pantoprazole. Depending on the different properties of the analyte molecules, dendritic core-shell glyco architectures showed (very) weak, moderate and strong interactions with the analyte molecules. Thus, ionic interactions are the strongest driving force for the formation of host-guest complexes. The core-shell glyco architecture is a necessary prerequisite for stable analyte/PEI complexes; the pure hyperbranched PEI did not show any sufficiently strong interactions with neutral, cationic or anionic analytes under the shear forces applied during ultrafiltration of pure aqueous solution without an adjusted pH. Thus, only robust non-covalent interactions between analytes and the dendritic polyamine scaffold of the glycopolymer structure survive this separation step and allow isolation of stable host-guest complexes in aqueous solution.

Cyclodextrin-modified dendritic polyamine (DexAM) construct for delivery of stem cell differentiation factors

Cyclodextrin-modified dendritic polyamine (DexAM) construct for delivery of stem cell differentiation factors

Single Vehicular Delivery of siRNA and Small Molecules to Control Stem Cell Differentiation

Achieving a controlled and reproducible means to direct stem cell differentiation is the single most critical concern scientists have been trying to address since the discovery of stem cells. In this regard, the use of small molecules and RNA interference offers unique advantages by targeting different cellular mechanisms. Our cyclodextrin-modified dendritic polyamine construct (termed DexAM) combines the unique properties of two distinct chemical moieties in a single delivery vehicle. DexAM is a single vehicle that not only solubilizes hydrophobic small molecules in physiological solutions but also forms complexes with siRNA molecules, making it an attractive delivery system for controlling stem cell differentiation. Herein, we report the synthesis and application of DexAM to simultaneously deliver hydrophobic small molecules and siRNA into neural stem cells to significantly enhance their neuronal differentiation.

Targeting EGFR for Treatment of Glioblastoma: Molecular Basis to Overcome Resistance

Glioblastoma (glioblastoma multiforme; GBM; WHO Grade IV) accounts for the majority of primary malignant brain tumors in adults. Amplification and mutation of the epidermal growth factor receptor (EGFR) gene represent signature genetic abnormalities encountered in GBM. A range of potential therapies that target EGFR or its mutant constitutively active form, ΔEGFR, including tyrosine kinase inhibitors (TKIs), monoclonal antibodies, vaccines, and RNA-based agents, are currently in development or in clinical trials for the treatment of GBM. Data from experimental studies evaluating these therapies have been very promising; however, their efficacy in the clinic has so far been limited by both upfront and acquired drug resistance. This review discusses the current status of anti-EGFR agents and the recurrent problem of resistance to these agents that strongly indicates that a multiple target approach will provide a more favorable future for these types of targeted therapies in GBM.

Advanced Functional Polymers for Medicine

Advanced Functional Polymers for Medicine

Synergistic Induction of Apoptosis in Brain Cancer Cells by Targeted Codelivery of siRNA and Anticancer Drugs

Multiple dysregulated pathways in tumors necessitate targeting multiple oncogenic elements by combining orthogonal therapeutic moieties like short-interfering RNAs (siRNA) and drug molecules in order to achieve a synergistic therapeutic effect. In this manuscript, we describe the synthesis of cyclodextrin-modified dendritic polyamines (DexAMs) and their application as a multicomponent delivery vehicle for translocating siRNA and anticancer drugs. The presence of β-cyclodextrins in our DexAMs facilitated complexation and intracellular uptake of hydrophobic anticancer drugs, suberoylanilide hydroxamic acid (SAHA) and erlotinib, whereas the cationic polyamine backbone allowed for electrostatic interaction with the negatively charged siRNA. The DexAM complexes were found to have minimal cytotoxicity over a wide range of concentrations and were found to efficiently deliver siRNA, thereby silencing the expression of targeted genes. As a proof of concept, we demonstrated that upon appropriate modification with targeting ligands, we were able to simultaneously deliver multiple payloads--siRNA against oncogenic receptor, EGFRvIII and anticancer drugs (SAHA or erlotinib)--efficiently and selectively to glioblastoma cells. Codelivery of siRNA-EGFRvIII and SAHA/erlotinib in glioblastoma cells was found to significantly inhibit cell proliferation and induce apoptosis, as compared to the individual treatments.

A Survey of Antiprion Compounds Reveals the Prevalence of Non-PrP Molecular Targets

Prion diseases are fatal neurodegenerative diseases caused by the accumulation of the misfolded isoform (PrP(Sc)) of the prion protein (PrP(C)). Cell-based screens have identified several compounds that induce a reduction in PrP(Sc) levels in infected cultured cells. However, the molecular targets of most antiprion compounds remain unknown. We undertook a large-scale, unbiased, cell-based screen for antiprion compounds and then investigated whether a representative subset of the active molecules had measurable affinity for PrP, increased the susceptibility of PrP(Sc) to proteolysis, or altered the cellular localization or expression level of PrP(C). None of the antiprion compounds showed in vitro affinity for PrP or had the ability to disaggregate PrP(Sc) in infected brain homogenates. These observations suggest that most antiprion compounds identified in cell-based screens deploy their activity via non-PrP targets in the cell. Our findings indicate that in comparison to PrP conformers themselves, proteins that play auxiliary roles in prion propagation may be more effective targets for future drug discovery efforts.

Dendritic Polyglycerols with Oligoamine Shells Show Low Toxicity and High siRNA Transfection Efficiency in Vitro

RNA interference provides great opportunities for treating diseases from genetic disorders, infection, and cancer. The successful application of small interference RNA (siRNA) in cells with high transfection efficiency and low cytotoxicity is, however, a major challenge in gene-mediated therapy. Several pH-responsive core shell architectures have been designed that contain a nitrogen shell motif and a polyglycerol core, which has been prepared by a two-step protocol involving the activation of primary and secondary hydroxyl groups by phenyl chloroformate and amine substitution. Each polymer was analyzed by particle size and ζ potential measurements, whereas the respective polyplex formation was determined by ethidium bromide displacement assay, atomic force microscopy (AFM), and surface charge analysis. The in vitro gene silencing properties of the different polymers were evaluated by using a human epithelial carcinoma cell (HeLaS3) line with different proteins (Lamin, CDC2, MAPK2). Polyplexes yielded similar knockdown efficiencies as HiPerFect controls, with comparably low cytotoxicity. Therefore, these efficient and highly biocompatible dendritic polyamines are promising candidates for siRNA delivery in vivo.

Dendritic polyamine architectures with lipophilic shells as nanocompartments for polar guest molecules: A comparative study of their transport behavior

AbstractDendritic core‐shell architectures were synthesized by simple melt reactions of polyethylenimine (PEI) with different fatty acids. These systems were investigated towards their ability to encapsulate various guest molecules. Parameters, such as the length of the attached alkyl chain, size of the polymer core, concentration of the core‐shell architecture in solution, pH, and nature of the guest molecule were investigated and compared. Guest molecules that bear anionic groups, such as carboxylate, phosphate, sulfonate, or acidic OH groups, as present in phenol units, are readily encapsulated and transferred from the aqueous phase to the organic phase because of multiple anionic–cationic interactions. Hyperbranched polymer architectures exhibit enhanced encapsulation properties when compared with their linear counterparts. In case of the hyperbranched system PEI25C16 amide higher transport capacities were observed at lower concentrations of the polymer, for example, 26 guest molecules at 10−5 mol L−1 versus 143 at 10−6 mol L−1, suggesting formation of larger aggregates. The aggregation behavior of these polar nanocompartments were investigated at different concentrations by AFM showing particle aggregates of typically 250 nm at a concentration of 10−5 M. The individual particle sizes in these aggregates are similar to the particle size at 10−6 M concentration, typically 4.0–5.5 nm (AFM height). This indicates that aggregate formation takes place at concentrations higher than 10−8 M and transport might be mediated by small aggregates rather than unimolecular particles. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 2287–2303, 2007

Synthesis and Electrochemistry of Octamethylferrocenyl-Functionalized Dendrimers

New octamethylferrocenyl dendritic macromolecules are reported. The condensation reaction of octamethylferrocenyl aldehyde (1) with dendritic polyamines DAB-dend-(NH2)x (x = 4, 8, 16, 32) affords up to the fourth generation of the octamethylferrocenylimine dendrimers DAB-dend-(NCHFc#)x (x = 4, 8, 16, 32) (2−5). Reduction of the imine groups leads to the corresponding octamethylferrocenylmethylamine dendrimers DAB-dend-(NHCH2Fc#)x (6−9) with 4, 8, 16, and 32 octamethylferrocenyl units per molecule, respectively. Characterization of the synthesized dendrimers by 1H and 13C{1H} NMR and IR spectroscopy, mass spectrometry, and elemental analysis supports their assigned structures. The redox activity of the octamethylferrocenyl centers in 6−9 has been characterized by cyclic voltammetry. Solution electrochemical studies showed that all the octamethylferrocenyl redox centers attached to the dendritic surface are electrochemically independent and that, in CH2Cl2 as solvent, the neutral dendrimers undergo oxidativ...

Synthesis of dendritic poly(urethane acrylate) used for UV-curable coatings

The UV-curable dendritic poly(urethane acrylate) (DPUA) was prepared from 2,4-toluene diisocyanate (TDI), β-hydroxyethyl arcylate (HEA) and dendritic polyamine (DPAM). The structure of the material was characterized by 1H NMR and FT-IR spectroscopes. The viscosity of the obtained products, the hardness, flexibility, curing speed, mechanical and thermal stability of UV-cured films were also examined. Results showed that this dendrimer has some superior properties and can be used for UV curing coating.

Highly Regioselective Synthesis of Amino-Functionalized Dendritic Polyglycerols by a One-Pot Hydroformylation/Reductive Amination Sequence

[reaction: see text] Dendritic architectures with neutral core structures and amines groups in the shell are a synthetic challenge, and there is a need for an efficient access. In this paper, highly selective Rh-catalysts are used for sequential hydroformylation/reductive amination of dendritic perallylated polyglycerols 1 with various amines in a one-pot procedure to give dendritic polyamines 3a-e in high yields (73-99%). In all cases, complete conversion of the allyl ether and aldehyde intermediate has been observed. Furthermore, the use of protected amines provides reactive core-shell-type architectures after deprotection. These soluble but membrane filterable multifunctional dendritic polyamines are of high interest as reagents in synthesis or as supports in homogeneous catalysis as well as nonviral vectors for DNA-transfection.

Dendritic polyamines: simple access to new materials with defined treelike structures for application in nonviral gene delivery.

Polycationic dendrimers are interesting nonviral vectors for in vitro DNA delivery. We describe a simple approach to the synthesis of dendritic polyamines with different molecular weights and adjustable flexibility (degrees of branching; DB). Both parameters influence the transfection efficiency and the cell toxicity of the polymer. Functionalization of hyperbranched polyethylenimine (PEI) by a two-step procedure generated fully branched pseudodendrimers (analogues of polypropylenimine (PPI) and polyamidoamine (PAMAM) dendrimers). The DNA transfection efficiencies observed for these polymers depended on the cell line investigated. The highest efficiencies were observed for polymers whose unfunctionalized PEI cores had molecular weights in the range M(w)=6000-25 000 g mol(-1). The cytotoxicity of the dendrimers generally rises with increasing core size. The data collected for NIH/3T3 and COS-7 cells indicate a maximum transfection efficiency at around 60 % branching for the PPI analogues, and at a PEI-core molecular weight of M(w)=25 000 g mol(-1). PAMAM functionalization of PEI (M(w)=5000 and 21 000 g mol(-1)) leads to polymers with little or no cytotoxity in the cell lines investigated.

Aligned monolayer assembly of zeolite crystals on platinum, gold, and indium–tin oxide surfaces with molecular linkages

Zeolite-A crystals with the average sizes of ∼0.5 × 0.5 × 0.5 μm and ∼1.7 × 1.7 × 1.7 μm and silicalite-1 crystals with the average size of ∼1.6 × 1.2 × 0.6 μm were synthesized, and 3-aminopropyl (AP) and 3-chloropropyl (CP) groups, respectively, were tethered on the surfaces of each zeolite. The AP-tethering zeolite microcrystals (Z–AP) readily self-assembled into uniformly aligned monolayers with high degrees of coverage (DOCs) and close packing (DCPs) on the surfaces of conducting substrates (CSs) such as platinum (Pt), gold (Au), and indium–tin oxide (ITO) glass upon refluxing the toluene solution of Z–AP and CSs for 3 h. The CP-tethering zeolite (Z–CP) crystals also readily self-assembled into uniformly aligned monolayers in high DOCs and DCPs on the surfaces of CSs that were pre-coated with the polymeric amines such as dendritic polyamine (DPA) and polyethylenimine (PEI), respectively. The binding strength of the zeolite microcrystals to CS increased in the order: Z–AP–CS < Z–CP–DPA–CS < Z–CP–PEI–CS for a given CS and a given type of zeolite, and ITO < Au ≅ Pt for a given molecular linkage and a given type of zeolite.

Reactivity of Acrylate-Terminated Au Nanoparticles: Suppressed Intramolecular Catalysis and Lack of Cooperative Effect

The cooperative effect in reactions of multifunctional compounds has been probed by monitoring the kinetics of the Michael addition of a dendritic polyamine to acrylate-terminated Au nanoparticles. Comparison of the kinetic data for this reaction with those for model monofunctional compounds showed the absence of any cooperativity. This was tentatively attributed to the high flexibility of the dendrimer and the inability of the system to bring mutually reactive functional groups sufficiently close to each other to achieve the rate enhancement effect. The subsequent reaction, methanolysis of the Michael adduct, was found to follow different mechanistic pathways in model monofunctional compounds and Au nanoparticles: while the model reaction undergoes intramolecular general base catalysis, no anchimeric assistance was observed for the reaction of Au nanoparticles. This difference in reactivity, which was attributed to steric effects, resulted in substantially different product distribution patterns for reactions of Au nanoparticles and model monofunctional compounds.