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Sample records for dendrimers multivalently presenting

  1. Collagen targeting using multivalent protein-functionalized dendrimers

    NARCIS (Netherlands)

    Breurken, M.; Lempens, E.H.M.; Temming, R.P.; Helms, B.A.; Meijer, E.W.; Merkx, M.

    2011-01-01

    Collagen is an attractive marker for tissue remodeling in a variety of common disease processes. Here we report the preparation of protein dendrimers as multivalent collagen targeting ligands by native chemical ligation of the collagen binding protein CNA35 to cysteine-functionalized dendritic

  2. SNAP dendrimers: multivalent protein display on dendrimer-like DNA for directed evolution.

    Science.gov (United States)

    Kaltenbach, Miriam; Stein, Viktor; Hollfelder, Florian

    2011-09-19

    Display systems connect a protein with the DNA encoding it. Such systems (e.g., phage or ribosome display) have found widespread application in the directed evolution of protein binders and constitute a key element of the biotechnological toolkit. In this proof-of-concept study we describe the construction of a system that allows the display of multiple copies of a protein of interest in order to take advantage of avidity effects during affinity panning. To this end, dendrimer-like DNA is used as a scaffold with docking points that can join the coding DNA with multiple protein copies. Each DNA construct is compartmentalised in water-in-oil emulsion droplets. The corresponding protein is expressed, in vitro, inside the droplets as a SNAP-tag fusion. The covalent bond between DNA and the SNAP-tag is created by reaction with dendrimer-bound benzylguanine (BG). The ability to form dendrimer-like DNA straightforwardly from oligonucleotides bearing BG allowed the comparison of a series of templates differing in size, valency and position of BG. In model selections the most efficient constructs show recoveries of up to 0.86 % and up to 400-fold enrichments. The comparison of mono- and multivalent constructs suggests that the avidity effect enhances enrichment by up to fivefold and recovery by up to 25-fold. Our data establish a multivalent format for SNAP-display based on dendrimer-like DNA as the first in vitro display system with defined tailor-made valencies and explore a new application for DNA nanostructures. These data suggest that multivalent SNAP dendrimers have the potential to facilitate the selection of protein binders especially during early rounds of directed evolution, allowing a larger diversity of candidate binders to be recovered. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Enhanced A3 adenosine receptor selectivity of multivalent nucleoside-dendrimer conjugates

    Directory of Open Access Journals (Sweden)

    Shainberg Asher

    2008-10-01

    Full Text Available Abstract Background An approach to use multivalent dendrimer carriers for delivery of nucleoside signaling molecules to their cell surface G protein-coupled receptors (GPCRs was recently introduced. Results A known adenosine receptor (AR agonist was conjugated to polyamidoamine (PAMAM dendrimer carriers for delivery of the intact covalent conjugate to on the cell surface. Depending on the linking moiety, multivalent conjugates of the N6-chain elongated functionalized congener ADAC (N6-[4-[[[4-[[[(2-aminoethylamino]carbonyl]methyl]anilino]carbonyl]methyl]phenyl]-adenosine achieved unanticipated high selectivity in binding to the cytoprotective human A3 AR, a class A GPCR. The key to this selectivity of > 100-fold in both radioreceptor binding (Ki app = 2.4 nM and functional assays (EC50 = 1.6 nM in inhibition of adenylate cyclase was maintaining a free amino group (secondary in an amide-linked chain. Attachment of neutral amide-linked chains or thiourea-containing chains preserved the moderate affinity and efficacy at the A1 AR subtype, but there was no selectivity for the A3 AR. Since residual amino groups on dendrimers are associated with cytotoxicity, the unreacted terminal positions of this A3 AR-selective G2.5 dendrimer were present as carboxylate groups, which had the further benefit of increasing water-solubility. The A3 AR selective G2.5 dendrimer was also visualized binding the membrane of cells expressing the A3 receptor but did not bind cells that did not express the receptor. Conclusion This is the first example showing that it is feasible to modulate and even enhance the pharmacological profile of a ligand of a GPCR based on conjugation to a nanocarrier and the precise structure of the linking group, which was designed to interact with distal extracellular regions of the 7 transmembrane-spanning receptor. This ligand tool can now be used in pharmacological models of tissue rescue from ischemia and to probe the existence of A3 AR

  4. IMMUNOSTIMULATORY PROPERTIES OF DENDRIMERS MULTIVALENTLY PRESENTING MURAMYLDIPEPTIDE

    DEFF Research Database (Denmark)

    Objectives: Many pathogens will only be efficiently neutralized by the induction of cell-mediated immunity, and with the enhanced use of subunit-vaccine approaches there is a strong need for the development of efficient and safe Th1-biassing adjuvants. Pathogen-associated molecular patterns (PAMPs...

  5. Dendrimers in drug research

    DEFF Research Database (Denmark)

    Boas, Ulrik; Heegaard, Peter M. H.

    2004-01-01

    and in vivo cytotoxicity, as well as biopermeability, biostability and immunogenicity. The review deals with numerous applications of dendrimers as tools for efficient multivalent presentation of biological ligands in biospecific recognition, inhibition and targeting. Dendrimers may be used as drugs...... for antibacterial and antiviral treatment and have found use as antitumor agents. The review highlights the use of dendrimers as drug or gene delivery devices in e.g. anticancer therapy, and the design of different host-guest binding motifs directed towards medical applications is described. Other specific examples...

  6. The adsorption-desorption transition of double-stranded DNA interacting with an oppositely charged dendrimer induced by multivalent anions.

    Science.gov (United States)

    Jiang, Yangwei; Zhang, Dong; Zhang, Yaoyang; Deng, Zhenyu; Zhang, Linxi

    2014-05-28

    The adsorption-desorption transition of DNA in DNA-dendrimer solutions is observed when high-valence anions, such as hexavalent anions, are added to the DNA-dendrimer solutions. In the DNA-dendrimer solutions with low-valence anions, dendrimers bind tightly with the V-shaped double-stranded DNA. When high-valence anions, such as pentavalent or hexavalent anions, are added to the DNA-dendrimer solutions, the double-stranded DNA chains can be stretched straightly and the dendrimers are released from the double-stranded DNA chains. In fact, adding high-valence anions to the solutions can change the charge spatial distribution in the DNA-dendrimer solutions, and weaken the electrostatic interactions between the positively charged dendrimers and the oppositely charged DNA chains. Adsorption-desorption transition of DNA is induced by the overcharging of dendrimers. This investigation is capable of helping us understand how to control effectively the release of DNA in gene/drug delivery because an effective gene delivery for dendrimers includes non-covalent DNA-dendrimer binding and the effective release of DNA in gene therapy.

  7. Noncovalent synthesis of protein dendrimers

    NARCIS (Netherlands)

    Lempens, E.H.M.; Baal, van I.; Dongen, van J.L.J.; Hackeng, T.M.; Merkx, M.; Meijer, E.W.

    2009-01-01

    The covalent synthesis of complex biomolecular systems such as multivalent protein dendrimers often proceeds with low efficiency, thereby making alternative strategies based on noncovalent chemistry of high interest. Here, the synthesis of protein dendrimers using a strong but noncovalent

  8. Multivalent contrast agents based on Gd-DTPA-terminated poly (propylene imine) dendrimers for Magnetic Resonance Imaging

    NARCIS (Netherlands)

    Langereis, S.; Lussanet, de Q.G; Genderen, van M.H.P.; Backes, W.H.; Meijer, E.W.

    2004-01-01

    A convenient methodol. has been developed for the synthesis of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA)-terminated poly(propylene imine) dendrimers as contrast agents for magnetic resonance imaging (MRI). In our strategy, isocyanate-activated, tert-butyl-protected DTPA analogs were

  9. Impact of multivalent charge presentation on peptide–nanoparticle aggregation

    Directory of Open Access Journals (Sweden)

    Daniel Schöne

    2015-05-01

    Full Text Available Strategies to achieve controlled nanoparticle aggregation have gained much interest, due to the versatility of such systems and their applications in materials science and medicine. In this article we demonstrate that coiled-coil peptide-induced aggregation based on electrostatic interactions is highly sensitive to the length of the peptide as well as the number of presented charges. The quaternary structure of the peptide was found to play an important role in aggregation kinetics. Furthermore, we show that the presence of peptide fibers leads to well-defined nanoparticle assembly on the surface of these macrostructures.

  10. Dendrimers for Vaccine and Immunostimulatory Uses

    DEFF Research Database (Denmark)

    Heegaard, Peter M. H.; Boas, Ulrik; Sørensen, Nanna Skall

    2010-01-01

    for efficient immunostimulating compounds (adjuvants) that can increase the efficiency of vaccines, as dendrimers can provide molecularly defined multivalent scaffolds to produce highly defined conjugates with small molecule immunostimulators and/or antigens. The review gives an overview on the use...... of dendrimers as molecularly defined carriers/presenters of small antigens, including constructs that have built-in immunostimulatory (adjuvant) properties, and as stand-alone adjuvants that can be mixed with antigens to provide efficient vaccine formulations. These approaches allow the preparation...... of molecularly defined vaccines with highly predictable and specific properties and enable knowledge-based vaccine design substituting the traditional empirically based approaches for vaccine development and production....

  11. Dendrimer Prodrugs

    Directory of Open Access Journals (Sweden)

    Soraya da Silva Santos

    2016-05-01

    Full Text Available The main objective of this review is to describe the importance of dendrimer prodrugs in the design of new drugs, presenting numerous applications of these nanocomposites in the pharmaceutical field. Therefore, the use of dendrimer prodrugs as carrier for drug delivery, to improve pharmacokinetic properties of prototype, to promote drug sustained-release, to increase selectivity and, consequently, to decrease toxicity, are just some examples of topics that have been extensively reported in the literature, especially in the last decade. The examples discussed here give a panel of the growing interest dendrimer prodrugs have been evoking in the scientific community.

  12. A review on comparative study of PPI and PAMAM dendrimers

    International Nuclear Information System (INIS)

    Kaur, Daljeet; Jain, Keerti; Mehra, Neelesh Kumar; Kesharwani, Prashant; Jain, Narendra K.

    2016-01-01

    Dendrimers are hyperbranched, monodispersed macromolecules with multivalent functional end groups. Dendrimers have been explored as carrier for many drugs like anticancer, antiviral, antimalarial, antiprotozoal, anti tubercular drugs. Although a number of different types of dendrimers containing different core molecules, branching monomers and surface functional groups have been designed till date for drug delivery applications, yet the poly(propyleneimine) (PPI) and poly(amidoamine) (PAMAM) dendrimers have been the most explored dendrimers in this regard. In this review, we have summarized a comparative data on PPI and PAMAM dendrimers particularly relevant to their properties, synthesis, toxicity, biomedical applications and drug delivery attributes.

  13. A review on comparative study of PPI and PAMAM dendrimers

    Energy Technology Data Exchange (ETDEWEB)

    Kaur, Daljeet; Jain, Keerti, E-mail: keertijain02@gmail.com; Mehra, Neelesh Kumar [ISF College of Pharmacy, Pharmaceutical Nanotechnology Research Laboratory (India); Kesharwani, Prashant [Wayne State University, Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences (United States); Jain, Narendra K., E-mail: jnarendr@yahoo.co.in, E-mail: dr.jnarendr@gmail.com [ISF College of Pharmacy, Pharmaceutical Nanotechnology Research Laboratory (India)

    2016-06-15

    Dendrimers are hyperbranched, monodispersed macromolecules with multivalent functional end groups. Dendrimers have been explored as carrier for many drugs like anticancer, antiviral, antimalarial, antiprotozoal, anti tubercular drugs. Although a number of different types of dendrimers containing different core molecules, branching monomers and surface functional groups have been designed till date for drug delivery applications, yet the poly(propyleneimine) (PPI) and poly(amidoamine) (PAMAM) dendrimers have been the most explored dendrimers in this regard. In this review, we have summarized a comparative data on PPI and PAMAM dendrimers particularly relevant to their properties, synthesis, toxicity, biomedical applications and drug delivery attributes.

  14. Multifunctional Dendrimer-templated Antibody Presentation on Biosensor Surfaces for Improved Biomarker Detection.

    Science.gov (United States)

    Han, Hye Jung; Kannan, Rangaramanujam M; Wang, Sunxi; Mao, Guangzhao; Kusanovic, Juan Pedro; Romero, Roberto

    2010-02-08

    Dendrimers, with their well-defined globular shape and a high density of functional groups, are ideal nanoscale materials for templating sensor surfaces. This work exploits dendrimers as a versatile platform for capturing biomarkers with improved sensitivity and specificity. Synthesis, characterization, fabrication, and functional validation of the dendrimer-based assay platform are described. Bifunctional hydroxyl/thiol functionalized G4-polyamidoamine (PAMAM) dendrimer is synthesized and immobilized on to the polyethylene-glycol (PEG)-functionalized assay plate by coupling PEG-maleimide and dendrimer thiol groups. Simultaneously, part of the dendrimer thiol groups are converted to hydrazide functionalities. The resulting dendrimer-modified surface is coupled to the capture antibody in the Fc region of the oxidized antibody. This preserves the orientation flexibility of the antigen binding region (Fv) of the antibody. To validate the approach, the fabricated plates are further used as a solid phase for developing a sandwich type ELISA to detect IL-6 and IL-1β, important biomarkers for early stages of chorioamnionitis. The dendrimer-modified plate provides assays with significantly enhanced sensitivity, lower nonspecific adsorption, and a detection limit of 0.13 pg ml -1 for IL-6 luminol detection and 1.15 pg ml -1 for IL-1β TMB detection, which are significantly better than those for the traditional ELISA. The assays were validated in human serum samples from normal (non-pregnant) woman and pregnant women with pyelonephritis. The specificity and the improved sensitivity of the dendrimer-based capture strategy could have significant implications for the detection of a wide range of cytokines and biomarkers since the capture strategy could be applied to multiplex microbead assays, conductometric immunosensors and field effect biosensors.

  15. Architecture effects on multivalent interactions by polypeptide-based multivalent ligands

    Science.gov (United States)

    Liu, Shuang

    Multivalent interactions are characterized by the simultaneous binding between multiple ligands and multiple binding sites, either in solutions or at interfaces. In biological systems, most multivalent interactions occur between protein receptors and carbohydrate ligands through hydrogen-bonding and hydrophobic interactions. Compared with weak affinity binding between one ligand and one binding site, i.e. monovalent interaction, multivalent interactioins provide greater avidity and specificity, and therefore play unique roles in a broad range of biological activities. Moreover, the studies of multivalent interactions are also essential for producing effective inhibitors and effectors of biological processes that could have important therapeutic applications. Synthetic multivalent ligands have been designed to mimic the biological functions of natural multivalent interactions, and various types of scaffolds have been used to display multiple ligands, including small molecules, linear polymers, dendrimers, nanoparticle surfaces, monolayer surfaces and liposomes. Studies have shown that multivalent interactions can be highly affected by various architectural parameters of these multivalent ligands, including ligand identities, valencies, spacing, ligand densities, nature of linker arms, scaffold length and scaffold conformation. Most of these multivalent ligands are chemically synthesized and have limitations of controlling over sequence and conformation, which is a barrier for mimicking ordered and controlled natural biological systems. Therefore, multivalent ligands with precisely controlled architecture are required for improved structure-function relationship studies. Protein engineering methods with subsequent chemical coupling of ligands provide significant advantages of controlling over backbone conformation and functional group placement, and therefore have been used to synthesize recombinant protein-based materials with desired properties similar to natural

  16. DENDRIMER CONJUGATES FOR SELECTIVE OF PROTEIN AGGREGATES

    DEFF Research Database (Denmark)

    2004-01-01

    Dendrimer conjugates are presented, which are formed between a dendrimer and a protein solubilising substance. Such dendrimer conjugates are effective in the treatment of protein aggregate-related diseases (e.g. prion-related diseases). The protein solubilising substance and the dendrimer together...

  17. Phosphorus dendrimers for nanomedicine.

    Science.gov (United States)

    Caminade, Anne-Marie

    2017-08-31

    From biomaterials to imaging, and from drug delivery to drugs by themselves, phosphorus-containing dendrimers offer a large palette of biological properties, depending essentially on their types of terminal functions. The most salient examples of phosphorus dendrimers used for the elaboration of bio-chips and of supports for cell cultures, for imaging biological events, and for carrying and delivering drugs or biomacromolecules are presented in this feature article. Several phosphorus dendrimers can be considered also as drugs per se (by themselves) in particular to fight against cancers, neurodegenerative diseases, and inflammation, both in vitro and in vivo. Toxicity assays are also reported.

  18. Polyphenylene dendrimers

    International Nuclear Information System (INIS)

    Marek, T.

    2002-01-01

    Complete text of publication follows. The most attractive property of polyphenylene dendrimers is their rigidity. They retain the molecular symmetry and monodispersity of the usual, commercially available alyphatic dendrimers, while the composition of the dendritic branches makes them self-supporting. In solution flexible dendrimers usually form a globular 3D-structure in which the dendritic branches are evenly distributed over the whole molecular volume, however, it has been shown that, depending on the generation of the particular dendrimer, their peripheral groups tend to fold back into the interior of the molecule. Moreover, when being adsorbed on a surface (or by the removal of the solvent), they often tend to flatten out. In contrast to this behaviour, it has been shown that rigid dendrimers based on polyphenylenes have stiff branches and the backfolding in solutions is impossible. Furthermore, when polyphenylene dendrimers are absorbed on a mica substrate their original shape is retained. These features and their size, lying in the low nanometer scale, make these molecules attractive candidates for several applications such as supports for functional groups and as hosts for smaller guest molecules. We have studied the free volume in a series of rigid polyphenylene dendrimers by positron lifetime spectroscopy (PLTS) and molecular dynamics calculations, in order to assess the expected relationship between the size (number of generations, molecular weight) of these molecules and the intramolecular free volume. We have found that the size of these inner free volumes is stable, and increases with the increasing number generations

  19. Anticancer copper(II) phosphorus dendrimers are potent proapoptotic Bax activators.

    Science.gov (United States)

    Mignani, Serge; El Brahmi, Nabil; Eloy, Laure; Poupon, Joel; Nicolas, Valérie; Steinmetz, Anke; El Kazzouli, Said; Bousmina, Mosto M; Blanchard-Desce, Mireille; Caminade, Anne-Marie; Majoral, Jean-Pierre; Cresteil, Thierry

    2017-05-26

    A multivalent phosphorus dendrimer 1G 3 and its corresponding Cu-complex, 1G 3 -Cu have been recently identified as agents retaining high antiproliferative potency. This antiproliferative capacity was preserved in cell lines overexpressing the efflux pump ABC B1, whereas cross-resistance was observed in ovarian cancer cell lines resistant to cisplatin. Theoretical 3D models were constructed: the dendrimers appear as irregularly shaped disk-like nano-objects of about 22 Å thickness and 49 Å diameter, which accumulated in cells after penetration by endocytosis. To get insight in their mode of action, cell death pathways have been examined in human cancer cell lines: early apoptosis was followed by secondary necrosis after multivalent phosphorus dendrimers exposure. The multivalent plain phosphorus dendrimer 1G 3 moderately activated caspase-3 activity, in contrast with the multivalent Cu-conjugated phosphorus dendrimer 1G 3 -Cu which strikingly reduced the caspase-3 content and activity. This decrease of caspase activity is not related to the presence of copper, since inorganic copper has no or little effect on caspase-3. Conversely the potent apoptosis activation could be related to a noticeable translocation of Bax to the mitochondria, resulting in the release of AIF into the cytosol, its translocation to the nucleus and a severe DNA fragmentation, without alteration of the cell cycle. The multivalent Cu-conjugated phosphorus dendrimer is more efficient than its non-complexed analog to activate this pathway in close relationship with the higher antiproliferative potency. Therefore, this multivalent Cu-conjugated phosphorus dendrimer 1G 3 -Cu can be considered as a new and promising first-in-class antiproliferative agent with a distinctive mode of action, inducing apoptosis tumor cell death through Bax activation pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Low-generation dendrimers with a calixarene core and based on a chiral C2-symmetric pyrrolidine as iminosugar mimics

    Directory of Open Access Journals (Sweden)

    Marco Marradi

    2012-06-01

    Full Text Available The preparation of low-generation dendrimers based on a simple calix[4]arene scaffold by insertion of the iminosugar-analogue C2-symmetric 3,4-dihydroxypyrrolidine is described. This methodology allows a rapid incorporation of a considerable number of iminosugar-like moieties in a reduced volume and in a well-defined geometry. The inclusion of alkali-metal ions (sodium and potassium in the polar cavity defined by the acetamide moieties at the lower rim of the calixarene was demonstrated, which allows also the rigidification of the dendrimer structure and the iminosugar presentation in the clusters. The combination of the supramolecular properties of calixarenes with the advantage of a dendrimeric presentation of repetitive units opens up the possibility of generating well-defined multivalent and multifaceted systems with more complex and/or biologically relevant iminosugars.

  1. Ordered Layered Dendrimers Constructed from Two Known Dendrimer Families: Inheritance and Emergence of Properties.

    Science.gov (United States)

    Dib, Hanna; Rebout, Cyrille; Laurent, Régis; Mallet-Ladeira, Sonia; Sournia-Saquet, Alix; Sárosi, Menyhárt B; Hey-Hawkins, Evamarie; Majoral, Jean-Pierre; Delavaux-Nicot, Béatrice; Caminade, Anne-Marie

    2016-07-25

    A new concept is presented, namely the synthesis of dendrimers intrinsically composed in alternation of building blocks pertaining to two known families of dendrimers: phosphorhydrazone dendrimers and triazine-piperazine dendrimers. These mixed dendrimers with layered controlled architecture inherit their easy (31) P NMR characterization and their thermal stability from the phosphorhydrazone family, and their decreased solubility from the triazine-piperazine family. However, they have also their own and original characteristics. Both parent families are white powders, whereas the mixed dendrimers are yellow, orange, or red powders, depending on the generation. DFT calculations were carried out on model dendrons to understand these special color features. Remarkably, these dendrimers incorporating redox-active organic entities allow for the first time the monitoring of the growth of an organic dendrimer by electrochemistry while highlighting an even-odd generation behavior. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Stability of anionic polymers in presence of multivalent cations

    International Nuclear Information System (INIS)

    Sabbagh, Imad

    1997-01-01

    The objectives of this research thesis were to study the stability of poly-electrolytes in saline environments, and the interactions between ions and poly-electrolytes of different charge densities. After a recall of the properties of neutral polymers and of poly-electrolytes in solution, the author evokes the interactions between poly-electrolytes and counter-ions, and briefly presents two models of stability of poly-electrolytes in saline solutions. Then, he presents different experimental techniques (scattering techniques and electrochemical techniques) and the results obtained when characterizing the used compounds. In the next part, the author discusses the basic differences of solubility between poly-electrolytes with sulfonate or sulfate groups and those with carboxylate groups. A simple model, inspired by the electrostatic model, allows poly-electrolyte phase diagram to be generalised with respect to the chemical affinity of its functional group with ions of opposed sign. The author then reports the study of the behaviour of non-charged poly-acrylic acid in various saline solutions, and then checks the behaviour of this acid within an intermediate range of dissociation level. The poly-acrylic acid structure and the distribution of ions before de-mixing are studied by X-ray and neutron scattering. The author finally tries to understand what is going on when multivalent cations are replaced by positively charged nano-metric particles (dendrimers) [fr

  3. Multivalent scaffolds induce galectin-3 aggregation into nanoparticles

    Directory of Open Access Journals (Sweden)

    Candace K. Goodman

    2014-07-01

    Full Text Available Galectin-3 meditates cell surface glycoprotein clustering, cross linking, and lattice formation. In cancer biology, galectin-3 has been reported to play a role in aggregation processes that lead to tumor embolization and survival. Here, we show that lactose-functionalized dendrimers interact with galectin-3 in a multivalent fashion to form aggregates. The glycodendrimer–galectin aggregates were characterized by dynamic light scattering and fluorescence microscopy methodologies and were found to be discrete particles that increased in size as the dendrimer generation was increased. These results show that nucleated aggregation of galectin-3 can be regulated by the nucleating polymer and provide insights that improve the general understanding of the binding and function of sugar-binding proteins.

  4. Interaction studies reveal specific recognition of an anti-inflammatory polyphosphorhydrazone dendrimer by human monocytes.

    Science.gov (United States)

    Ledall, Jérémy; Fruchon, Séverine; Garzoni, Matteo; Pavan, Giovanni M; Caminade, Anne-Marie; Turrin, Cédric-Olivier; Blanzat, Muriel; Poupot, Rémy

    2015-11-14

    Dendrimers are nano-materials with perfectly defined structure and size, and multivalency properties that confer substantial advantages for biomedical applications. Previous work has shown that phosphorus-based polyphosphorhydrazone (PPH) dendrimers capped with azabisphosphonate (ABP) end groups have immuno-modulatory and anti-inflammatory properties leading to efficient therapeutic control of inflammatory diseases in animal models. These properties are mainly prompted through activation of monocytes. Here, we disclose new insights into the molecular mechanisms underlying the anti-inflammatory activation of human monocytes by ABP-capped PPH dendrimers. Following an interdisciplinary approach, we have characterized the physicochemical and biological behavior of the lead ABP dendrimer with model and cell membranes, and compared this experimental set of data to predictive computational modelling studies. The behavior of the ABP dendrimer was compared to the one of an isosteric analog dendrimer capped with twelve azabiscarboxylate (ABC) end groups instead of twelve ABP end groups. The ABC dendrimer displayed no biological activity on human monocytes, therefore it was considered as a negative control. In detail, we show that the ABP dendrimer can bind both non-specifically and specifically to the membrane of human monocytes. The specific binding leads to the internalization of the ABP dendrimer by human monocytes. On the contrary, the ABC dendrimer only interacts non-specifically with human monocytes and is not internalized. These data indicate that the bioactive ABP dendrimer is recognized by specific receptor(s) at the surface of human monocytes.

  5. Comparison of generation 3 polyamidoamine dendrimer and generation 4 polypropylenimine dendrimer on drug loading, complex structure, release behavior, and cytotoxicity

    Science.gov (United States)

    Shao, Naimin; Su, Yunzhang; Hu, Jingjing; Zhang, Jiahai; Zhang, Hongfeng; Cheng, Yiyun

    2011-01-01

    Background Polyamidoamine (PAMAM) and polypropylenimine (PPI) dendrimers are the commercially available and most widely used dendrimers in pharmaceutical sciences and biomedical engineering. In the present study, the loading and release behaviors of generation 3 PAMAM and generation 4 PPI dendrimers with the same amount of surface amine groups (32 per dendrimer) were compared using phenylbutazone as a model drug. Methods The dendrimer-phenylbutazone complexes were characterized by 1H nuclear magnetic resonance and nuclear Overhauser effect techniques, and the cytotoxicity of each dendrimer was evaluated. Results Aqueous solubility results suggest that the generation 3 PAMAM dendrimer has a much higher loading ability towards phenylbutazone in comparison with the generation 4 PPI dendrimer at high phenylbutazone-dendrimer feeding ratios. Drug release was much slower from the generation 3 PAMAM matrix than from the generation 4 PPI dendrimer. In addition, the generation 3 PAMAM dendrimer is at least 50-fold less toxic than generation 4 PPI dendrimer on MCF-7 and A549 cell lines. Conclusion Although the nuclear Overhauser effect nuclear magnetic resonance results reveal that the generation 4 PPI dendrimer with a more hydrophobic interior encapsulates more phenylbutazone, the PPI dendrimer-phenylbutazone inclusion is not stable in aqueous solution, which poses a great challenge during drug development. PMID:22267921

  6. Peptide dendrimers

    Czech Academy of Sciences Publication Activity Database

    Niederhafner, Petr; Šebestík, Jaroslav; Ježek, Jan

    2005-01-01

    Roč. 11, - (2005), 757-788 ISSN 1075-2617 R&D Projects: GA ČR(CZ) GA203/03/1362 Institutional research plan: CEZ:AV0Z40550506 Keywords : multiple antigen peptides * peptide dendrimers * synthetic vaccine * multipleantigenic peptides Subject RIV: CC - Organic Chemistry Impact factor: 1.803, year: 2005

  7. Multivalent dendrimeric compounds containing carbohydrates expressed on immune cells inhibit infection by primary isolates of HIV-1

    Science.gov (United States)

    Borges, Andrew Rosa; Wieczorek, Lindsay; Johnson, Benitra; Benesi, Alan J.; Brown, Bruce K.; Kensinger, Richard D.; Krebs, Fred C.; Wigdahl, Brian; Blumenthal, Robert; Puri, Anu; McCutchan, Francine E.; Birx, Deborah L.; Polonis, Victoria R.; Schengrund, Cara-Lynne

    2010-01-01

    Specific glycosphingolipids (GSL), found on the surface of target immune cells, are recognized as alternate cell surface receptors by the human immunodeficiency virus type 1 (HIV-1) external envelope glycoprotein. In this study, the globotriose and 3’-sialyllactose carbohydrate head groups found on two GSL were covalently attached to a dendrimer core to produce two types of unique multivalent carbohydrates (MVC). These MVC inhibited HIV-1 infection of T cell lines and primary peripheral blood mononuclear cells (PBMC) by T cell line-adapted viruses or primary isolates, with IC50s ranging from 0.1 – 7.4 µg/ml. Inhibition of Env-mediated membrane fusion by MVC was also observed using a dye-transfer assay. These carbohydrate compounds warrant further investigation as a potential new class of HIV-1 entry inhibitors. The data presented also shed light on the role of carbohydrate moieties in HIV-1 virus-host cell interactions. PMID:20880566

  8. PREPARATION OF CHEMICALLY WELL-DEFINED CARBOHYDRATE DENDRIMER CONJUGATES

    DEFF Research Database (Denmark)

    2004-01-01

    A method for the synthesis of dendrimer conjugates having a well-defined chemical structure, comprising one or more carbohydrate moieties and one or more immunomodulating substances coupled to a dendrimer, is presented. First, the carbohydrate is bound to the dendrimer in a chemoselective manner...... conjugates and their use in vaccination, production of antibodies, high throughput screening, diagnostic assays and libraries....

  9. DNA assisted self-assembly of PAMAM dendrimers.

    Science.gov (United States)

    Mandal, Taraknath; Kumar, Mattaparthi Venkata Satish; Maiti, Prabal K

    2014-10-09

    We report DNA assisted self-assembly of polyamidoamine (PAMAM) dendrimers using all atom Molecular Dynamics (MD) simulations and present a molecular level picture of a DNA-linked PAMAM dendrimer nanocluster, which was first experimentally reported by Choi et al. (Nano Lett., 2004, 4, 391-397). We have used single stranded DNA (ssDNA) to direct the self-assembly process. To explore the effect of pH on this mechanism, we have used both the protonated (low pH) and nonprotonated (high pH) dendrimers. In all cases studied here, we observe that the DNA strand on one dendrimer unit drives self-assembly as it binds to the complementary DNA strand present on the other dendrimer unit, leading to the formation of a DNA-linked dendrimer dimeric complex. However, this binding process strongly depends on the charge of the dendrimer and length of the ssDNA. We observe that the complex with a nonprotonated dendrimer can maintain a DNA length dependent inter-dendrimer distance. In contrast, for complexes with a protonated dendrimer, the inter-dendrimer distance is independent of the DNA length. We attribute this observation to the electrostatic complexation of a negatively charged DNA strand with the positively charged protonated dendrimer.

  10. Multivalent dendrimeric compounds containing carbohydrates expressed on immune cells inhibit infection by primary isolates of HIV-1

    International Nuclear Information System (INIS)

    Rosa Borges, Andrew; Wieczorek, Lindsay; Johnson, Benitra; Benesi, Alan J.; Brown, Bruce K.; Kensinger, Richard D.; Krebs, Fred C.; Wigdahl, Brian; Blumenthal, Robert; Puri, Anu; McCutchan, Francine E.; Birx, Deborah L.; Polonis, Victoria R.; Schengrund, Cara-Lynne

    2010-01-01

    Specific glycosphingolipids (GSL), found on the surface of target immune cells, are recognized as alternate cell surface receptors by the human immunodeficiency virus type 1 (HIV-1) external envelope glycoprotein. In this study, the globotriose and 3'-sialyllactose carbohydrate head groups found on two GSL were covalently attached to a dendrimer core to produce two types of unique multivalent carbohydrates (MVC). These MVC inhibited HIV-1 infection of T cell lines and primary peripheral blood mononuclear cells (PBMC) by T cell line-adapted viruses or primary isolates, with IC 50 s ranging from 0.1 to 7.4 μg/ml. Inhibition of Env-mediated membrane fusion by MVC was also observed using a dye-transfer assay. These carbohydrate compounds warrant further investigation as a potential new class of HIV-1 entry inhibitors. The data presented also shed light on the role of carbohydrate moieties in HIV-1 virus-host cell interactions. -- Research Highlights: →Multivalent carbohydrates (MVCs) inhibited infection of PBMCs by HIV-1. →MVCs inhibited infection by T cell line-adapted viruses. →MVCs inhibited infection by primary isolates of HIV-1. →MVCs inhibited Env-mediated membrane fusion.

  11. Thin film properties of triphenylamine-cored dendrimers: A molecular approach to control aggregation

    Energy Technology Data Exchange (ETDEWEB)

    Vamvounis, George, E-mail: g.vamvounis@uq.edu.au; Pivrikas, Almantas; Shaw, Paul E.; Burn, Paul L.

    2013-12-02

    The solid-state photophysical and charge transport properties of two first-generation dendrimers are presented. The dendrimers are comprised of a triphenylamine core, dendrons containing a phenyl branching unit with thiophene (Dendrimer 1) or bithiophene (Dendrimer 2) moieties, and dodecyl surface groups. For Dendrimer 1, the excited state is located within the center of the dendrimer giving rise to a moderate solid-state photoluminescence quantum yield (Φ{sub pl}) (0.13) and significant charge trapping, with both observations due to the degree of overlap of the main electroactive chromophores on adjacent dendrimers. For Dendrimer 2, the excited state is located within the dendron and in the solid-state this leads to a strongly red-shifted and weakened emission (Φ{sub pl} ∼ 0.02) due to strong intermolecular chromophore interactions. For films of Dendrimer 2 the charge mobility was higher than Dendrimer 1 but was still limited by a low density of strongly interacting electroactive chromophores. The pronounced difference between the solid-state properties of the two dendrimers is simply engineered by the addition of an extra thiophene in each of the dendrons. - Highlights: • Photophysical and charge-transport properties of two dendrimers are investigated. • Excited-state is on the center for Dendrimer 1 and on the dendron for Dendrimer 2. • Film quantum yield of luminescence is higher for Dendrimer 1. • Dendrimer 1 displays greater charge trapping at high fields.

  12. Thin film properties of triphenylamine-cored dendrimers: A molecular approach to control aggregation

    International Nuclear Information System (INIS)

    Vamvounis, George; Pivrikas, Almantas; Shaw, Paul E.; Burn, Paul L.

    2013-01-01

    The solid-state photophysical and charge transport properties of two first-generation dendrimers are presented. The dendrimers are comprised of a triphenylamine core, dendrons containing a phenyl branching unit with thiophene (Dendrimer 1) or bithiophene (Dendrimer 2) moieties, and dodecyl surface groups. For Dendrimer 1, the excited state is located within the center of the dendrimer giving rise to a moderate solid-state photoluminescence quantum yield (Φ pl ) (0.13) and significant charge trapping, with both observations due to the degree of overlap of the main electroactive chromophores on adjacent dendrimers. For Dendrimer 2, the excited state is located within the dendron and in the solid-state this leads to a strongly red-shifted and weakened emission (Φ pl ∼ 0.02) due to strong intermolecular chromophore interactions. For films of Dendrimer 2 the charge mobility was higher than Dendrimer 1 but was still limited by a low density of strongly interacting electroactive chromophores. The pronounced difference between the solid-state properties of the two dendrimers is simply engineered by the addition of an extra thiophene in each of the dendrons. - Highlights: • Photophysical and charge-transport properties of two dendrimers are investigated. • Excited-state is on the center for Dendrimer 1 and on the dendron for Dendrimer 2. • Film quantum yield of luminescence is higher for Dendrimer 1. • Dendrimer 1 displays greater charge trapping at high fields

  13. Dendrimers for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Abhay Singh Chauhan

    2018-04-01

    Full Text Available Dendrimers have come a long way in the last 25 years since their inception. Originally created as a wonder molecule of chemistry, dendrimer is now in the fourth class of polymers. Dr. Donald Tomalia first published his seminal work on Poly(amidoamine (PAMAM dendrimers in 1985. Application of dendrimers as a drug delivery system started in late 1990s. Dendrimers for drug delivery are employed using two approaches: (i formulation and (ii nanoconstruct. In the formulation approach, drugs are physically entrapped in a dendrimer using non-covalent interactions, whereas drugs are covalently coupled on dendrimers in the nanoconstruct approach. We have demonstrated the utility of PAMAM dendrimers for enhancing solubility, stability and oral bioavailability of various drugs. Drug entrapment and drug release from dendrimers can be controlled by modifying dendrimer surfaces and generations. PAMAM dendrimers are also shown to increase transdermal permeation and specific drug targeting. Dendrimer platforms can be engineered to attach targeting ligands and imaging molecules to create a nanodevice. Dendrimer nanotechnology, due to its multifunctional ability, has the potential to create next generation nanodevices.

  14. Pharmaceutical and biomedical potential of surface engineered dendrimers.

    Science.gov (United States)

    Satija, Jitendra; Gupta, Umesh; Jain, Narendra Kumar

    2007-01-01

    Dendrimers are hyperbranched, globular, monodisperse, nanometric polymeric architecture, having definite molecular weight, shape, and size (which make these an inimitable and optimum carrier molecule in pharmaceutical field). Dendritic architecture is having immense potential over the other carrier systems, particularly in the field of drug delivery because of their unique properties, such as structural uniformity, high purity, efficient membrane transport, high drug pay load, targeting potential, and good colloidal, biological, and shelf stability. Despite their enormous applicability in different areas, the inherent cytotoxicity, reticuloendothelial system (RES) uptake, drug leakage, immunogenicity, and hemolytic toxicity restricted their use in clinical applications, which is primarily associated with cationic charge present on the periphery due to amine groups. To overcome this toxic nature of dendrimers, some new types of nontoxic, biocompatible, and biodegradable dendrimers have been developed (e.g., polyester dendrimer, citric acid dendrimer, arginine dendrimer, carbohydrate dendrimers, etc.). The surface engineering of parent dendrimers is graceful and convenient strategy, which not only shields the positive charge to make this carrier more biomimetic but also improves the physicochemical and biological behavior of parent dendrimers. Thus, surface modification chemistry of parent dendrimers holds promise in pharmaceutical applications (such as solubilization, improved drug encapsulation, enhanced gene transfection, sustained and controlled drug release, intracellular targeting) and in the diagnostic field. Development of multifunctional dendrimer holds greater promise toward the biomedical applications because a number of targeting ligands determine specificity in the same manner as another type of group would secure stability in biological milieu and prolonged circulation, whereas others facilitate their transport through cell membranes. Therefore, as a

  15. Optical absorption in dendrimers

    International Nuclear Information System (INIS)

    Supritz, C.; Engelmann, A.; Reineker, P.

    2004-01-01

    Dendrimers are highly branched molecules, which are expected to be useful, for example, as efficient artificial light harvesting systems in nano-technological applications. There are two different classes of dendrimers: compact dendrimers with constant distance between neighboring branching points throughout the macromolecule and extended dendrimers, where this distance increases from the system periphery to the center. We investigate the linear absorption spectra of these dendrimer types using the Frenkel exciton concept. The electron-phonon interaction is taken into account by introducing a heat bath that interacts with the exciton in a stochastic manner

  16. Multivalency in supramolecular chemistry and nanofabrication

    NARCIS (Netherlands)

    Mulder, A.; Huskens, Jurriaan; Reinhoudt, David

    2004-01-01

    Multivalency is a powerful and versatile self-assembly pathway that confers unique thermodynamic and kinetic behavior onto supramolecular complexes. The diversity of the examples of supramolecular multivalent systems discussed in this perspective shows that the concept of multivalency is a general

  17. Stopped-flow kinetic studies of poly(amidoamine) dendrimer-calf thymus DNA to form dendriplexes.

    Science.gov (United States)

    Dey, Debabrata; Kumar, Santosh; Maiti, Souvik; Dhara, Dibakar

    2013-11-07

    Poly(amidoamine) (PAMAM) dendrimers are known to be highly efficient nonviral carriers in gene delivery. Dendrimer-mediated transfection is known to be a function of the dendrimer to DNA charge ratio as well as the size of the dendrimer. In the present study, the binding kinetics of four PAMAM dendrimers (G1, G2, G3, and G4) with calf thymus DNA (CT-DNA) has been studied using stopped-flow fluorescence spectroscopy. The effect of dendrimer-to-DNA charge ratio and dendrimer generation on the binding kinetics was investigated. In most cases, the results of dendrimer-CT-DNA binding can be explained by a two-step reaction mechanism: a rapid electrostatic binding between the dendrimer and DNA, followed by a conformational change of the dendrimer-DNA complex that ultimately leads to DNA condensation. It was observed that the charge ratio on the dendrimer and the DNA phosphate groups, as well as the dendrimer generation (size), has a marked effect on the kinetics of binding between the DNA and the dendrimers. The rate constant (k'1) of the first step was much higher compared to that of the second step (k'2), and both were found to increase with an increase in dendrimer concentration. Among the four generations of dendrimers, G4 exhibited significantly faster binding kinetics compared to the three smaller generation dendrimers.

  18. On certain subclasses of multivalent functions associated with an extended fractional differintegral operator

    Science.gov (United States)

    Patel, J.; Mishra, A. K.

    2007-08-01

    In the present paper an extended fractional differintegral operator , suitable for the study of multivalent functions is introduced. Various mapping properties and inclusion relationships between certain subclasses of multivalent functions are investigated by applying the techniques of differential subordination. Relevant connections of the definitions and results presented in this paper with those obtained in several earlier works on the subject are also pointed out.

  19. Inhibition of the norepinephrine transporter by χ-conotoxin dendrimers.

    Science.gov (United States)

    Wan, Jingjing; Brust, Andreas; Bhola, Rebecca F; Jha, Prerna; Mobli, Mehdi; Lewis, Richard J; Christie, Macdonald J; Alewood, Paul F

    2016-05-01

    Peptide dendrimers are a novel class of macromolecules of emerging interest with the potential of delayed renal clearance due to their molecular size and enhanced activity due to the multivalency effect. In this work, an active analogue of the disulfide-rich χ-conotoxin χ-MrIA (χ-MrIA), a norepinephrine reuptake (norepinephrine transporter) inhibitor, was grafted onto a polylysine dendron. Dendron decoration was achieved by employing copper-catalyzed alkyne-azide cycloaddition with azido-PEG chain-modified χ-MrIA analogues, leading to homogenous 4-mer and 8-mer χ-MrIA dendrimers with molecular weights ranging from 8 to 22 kDa. These dendrimers were investigated for their impact on peptide secondary structure, in vitro functional activity, and potential anti-allodynia in vivo. NMR studies showed that the χ-MrIA tertiary structure was maintained in the χ-MrIA dendrimers. In a functional norepinephrine transporter reuptake assay, χ-MrIA dendrimers showed slightly increased potency relative to the azido-PEGylated χ-MrIA analogues with similar potency to the parent peptide. In contrast to χ-MrIA, no anti-allodynic action was observed when the χ-MrIA dendrimers were administered intrathecally in a rat model of neuropathic pain, suggesting that the larger dendrimer structures are unable to diffuse through the spinal column tissue and reach the norepinephrine transporter. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

  20. Charge transport in highly efficient iridium cored electrophosphorescent dendrimers

    Science.gov (United States)

    Markham, Jonathan P. J.; Samuel, Ifor D. W.; Lo, Shih-Chun; Burn, Paul L.; Weiter, Martin; Bässler, Heinz

    2004-01-01

    Electrophosphorescent dendrimers are promising materials for highly efficient light-emitting diodes. They consist of a phosphorescent core onto which dendritic groups are attached. Here, we present an investigation into the optical and electronic properties of highly efficient phosphorescent dendrimers. The effect of dendrimer structure on charge transport and optical properties is studied using temperature-dependent charge-generation-layer time-of-flight measurements and current voltage (I-V) analysis. A model is used to explain trends seen in the I-V characteristics. We demonstrate that fine tuning the mobility by chemical structure is possible in these dendrimers and show that this can lead to highly efficient bilayer dendrimer light-emitting diodes with neat emissive layers. Power efficiencies of 20 lm/W were measured for devices containing a second-generation (G2) Ir(ppy)3 dendrimer with a 1,3,5-tris(2-N-phenylbenzimidazolyl)benzene electron transport layer.

  1. Glycopeptide dendrimers. Part I

    Czech Academy of Sciences Publication Activity Database

    Niederhafner, Petr; Šebestík, Jaroslav; Ježek, Jan

    2008-01-01

    Roč. 14, č. 1 (2008), s. 2-43 ISSN 1075-2617 R&D Projects: GA ČR GA203/03/1362; GA ČR GA203/06/1272; GA MZe QF3115; GA AV ČR KAN200520703 Institutional research plan: CEZ:AV0Z40550506 Keywords : artificial virus * calixarene dendrimers * carbopeptide dendrimers * glycopeptide dendrimers Subject RIV: CC - Organic Chemistry Impact factor: 1.654, year: 2008

  2. Optimization of carboxylate-terminated poly(amidoamine) dendrimer-mediated cisplatin formulation.

    Science.gov (United States)

    Kulhari, Hitesh; Pooja, Deep; Singh, Mayank K; Chauhan, Abhay S

    2015-02-01

    Abstract Cisplatin is mainly used in the treatment of ovarian, head and neck and testicular cancer. Poor solubility and non-specific interactions causes hurdles in the development of successful cisplatin formulation. There were few reports on poly(amidoamine) (PAMAM) dendrimer-cisplatin complexes for anticancer treatment. But the earlier research was mainly focused on therapeutic effect of PAMAM dendrimer-cisplatin complex, with less attention paid on the formulation development of these complexes. Objective of the present study is to optimize and validate the carboxylate-terminated, EDA core PAMAM dendrimer-based cisplatin formulation with respect to various variables such as dendrimer core, generation, drug entrapment, purification, yield, reproducibility, stability, storage and in-vitro release. Dendrimer-cisplatin complex was prepared by an efficient method which significantly increases the % platinum (Pt) content along with the product yield. Dendrimers showed reproducible (∼27%) platinum loading by weight. Variation in core and generations does not produce significant change in the % Pt content. Percentage Pt content of dendrimeric formulation increases with increase in drug/dendrimer mole ratio. Formulation with low drug/dendrimer mole ratio showed delayed release compared to the higher drug/dendrimer mole ratio; these dendrimer formulations are stable in room temperature. In vitro release profiles of the stored dendrimer-cisplatin samples showed comparatively slow release of cisplatin, which may be due to formation of strong bond between cisplatin and dendrimer. This study will contribute to create a fine print for the formulation development of PAMAM dendrimer-cisplatin complexes.

  3. On the ability of PAMAM dendrimers and dendrimer/DNA aggregates to penetrate POPC model biomembranes.

    Science.gov (United States)

    Ainalem, Marie-Louise; Campbell, Richard A; Khalid, Syma; Gillams, Richard J; Rennie, Adrian R; Nylander, Tommy

    2010-06-03

    Poly(amido amine) (PAMAM) dendrimers have previously been shown, as cationic condensing agents of DNA, to have high potential for nonviral gene delivery. This study addresses two key issues for gene delivery: the interaction of the biomembrane with (i) the condensing agent (the cationic PAMAM dendrimer) and (ii) the corresponding dendrimer/DNA aggregate. Using in situ null ellipsometry and neutron reflection, parallel experiments were carried out involving dendrimers of generations 2 (G2), 4 (G4), and 6 (G6). The study demonstrates that free dendrimers of all three generations were able to traverse supported palmitoyloleoylphosphatidylcholine (POPC) bilayers deposited on silica surfaces. The model biomembranes were elevated from the solid surfaces upon dendrimer penetration, which offers a promising new way to generate more realistic model biomembranes where the contact with the supporting surface is reduced and where aqueous cavities are present beneath the bilayer. The largest dendrimer (G6) induced partial bilayer destruction directly upon penetration, whereas the smaller dendrimers (G2 and G4) leave the bilayer intact, so we propose that lower generation dendrimers have greater potential as transfection mediators. In addition to the experimental observations, coarse-grained simulations on the interaction between generation 3 (G3) dendrimers and POPC bilayers were performed in the absence and presence of a bilayer-supporting negatively charged surface that emulates the support. The simulations demonstrate that G3 is transported across free-standing POPC bilayers by direct penetration and not by endocytosis. The penetrability was, however, reduced in the presence of a surface, indicating that the membrane transport observed experimentally was not driven solely by the surface. The experimental reflection techniques were also applied to dendrimer/DNA aggregates of charge ratio = 0.5, and while G2/DNA and G4/DNA aggregates interact with POPC bilayers, G6/DNA

  4. Energy transport in dendrimers

    International Nuclear Information System (INIS)

    Supritz, C.; Engelmann, A.; Reineker, P.

    2006-01-01

    Dendrimers are highly branched polymers which are expected to be useful, for example, as efficient artificial light harvesting systems in nano-technological applications. There are two different classes of dendrimers: compact dendrimers with constant distance between neighboring branching points throughout the macromolecule and extended dendrimers where this distance increases from the system periphery to the center. An open question is still whether energy transport (via Frenkel excitons) occurs in a coherent or incoherent manner. We model the hyperbranched dendrimer molecule as an arrangement of two-level systems and apply the Frenkel exciton concept. The two-level systems are interacting with each other via transfer integrals modeling the special spatial structure of dendrimers. To take into account the electron-phonon interaction we introduce a heat bath that interacts with the exciton in a stochastic manner. In this way we describe the coupled coherent and incoherent Frenkel exciton transport inside a dendrimer. In order to mimic the influence of an energy capturing reaction center (like in photosynthesis) on exciton transport, we attach a sink to the dendrimer core

  5. Energy transport in dendrimers

    Energy Technology Data Exchange (ETDEWEB)

    Supritz, C. [Abteilung Theoretische Physik, Universitaet Ulm, Albert-Einstein-Allee 11, 89069 Ulm (Germany)]. E-mail: christoph.supritz@uni-ulm.de; Engelmann, A. [Abteilung Theoretische Physik, Universitaet Ulm, Albert-Einstein-Allee 11, 89069 Ulm (Germany); Reineker, P. [Abteilung Theoretische Physik, Universitaet Ulm, Albert-Einstein-Allee 11, 89069 Ulm (Germany)

    2006-07-15

    Dendrimers are highly branched polymers which are expected to be useful, for example, as efficient artificial light harvesting systems in nano-technological applications. There are two different classes of dendrimers: compact dendrimers with constant distance between neighboring branching points throughout the macromolecule and extended dendrimers where this distance increases from the system periphery to the center. An open question is still whether energy transport (via Frenkel excitons) occurs in a coherent or incoherent manner. We model the hyperbranched dendrimer molecule as an arrangement of two-level systems and apply the Frenkel exciton concept. The two-level systems are interacting with each other via transfer integrals modeling the special spatial structure of dendrimers. To take into account the electron-phonon interaction we introduce a heat bath that interacts with the exciton in a stochastic manner. In this way we describe the coupled coherent and incoherent Frenkel exciton transport inside a dendrimer. In order to mimic the influence of an energy capturing reaction center (like in photosynthesis) on exciton transport, we attach a sink to the dendrimer core.

  6. Multivalent presentation of MPL by porous silicon microparticles favors T helper 1 polarization enhancing the anti-tumor efficacy of doxorubicin nanoliposomes.

    Science.gov (United States)

    Meraz, Ismail M; Hearnden, Claire H; Liu, Xuewu; Yang, Marie; Williams, Laura; Savage, David J; Gu, Jianhua; Rhudy, Jessica R; Yokoi, Kenji; Lavelle, Ed C; Serda, Rita E

    2014-01-01

    Porous silicon (pSi) microparticles, in diverse sizes and shapes, can be functionalized to present pathogen-associated molecular patterns that activate dendritic cells. Intraperitoneal injection of MPL-adsorbed pSi microparticles, in contrast to free MPL, resulted in the induction of local inflammation, reflected in the recruitment of neutrophils, eosinophils and proinflammatory monocytes, and the depletion of resident macrophages and mast cells at the injection site. Injection of microparticle-bound MPL resulted in enhanced secretion of the T helper 1 associated cytokines IFN-γ and TNF-α by peritoneal exudate and lymph node cells in response to secondary stimuli while decreasing the anti-inflammatory cytokine IL-10. MPL-pSi microparticles independently exhibited anti-tumor effects and enhanced tumor suppression by low dose doxorubicin nanoliposomes. Intravascular injection of the MPL-bound microparticles increased serum IL-1β levels, which was blocked by the IL-1 receptor antagonist Anakinra. The microparticles also potentiated tumor infiltration by dendritic cells, cytotoxic T lymphocytes, and F4/80+ macrophages, however, a specific reduction was observed in CD204+ macrophages.

  7. Host-guest chemistry of dendrimer-drug complexes. 4. An in-depth look into the binding/encapsulation of guanosine monophosphate by dendrimers.

    Science.gov (United States)

    Hu, Jingjing; Fang, Min; Cheng, Yiyun; Zhang, Jiahai; Wu, Qinglin; Xu, Tongwen

    2010-06-03

    In the present study, we investigated the host-guest chemistry of dendrimer/guanosine monophosphate (GMP) and present an in-depth look into the binding/encapsulation of GMP by dendrimers using NMR studies. (1)H NMR spectra showed a significant downfield shift of methylene protons in the outmost layer of the G5 dendrimer, indicating the formation of ion pairs between cationic amine groups of dendrimer and anionic phosphate groups of GMP. Chemical shift titration results showed that the binding constant between G5 dendrimer and GMP is 17,400 M(-1) and each G5 dendrimer has 107 binding sites. The binding of GMP to dendrimers prevents its aggregation in aqueous solutions and thereby enhances its stability. Nuclear Overhauser effect measurements indicated that a GMP binding and encapsulation balance occurs on the surface and in the interior of dendrimer. The binding/encapsulation transitions can be easily tailored by altering the surface and interior charge densities of the dendrimer. All these findings provide a new insight into the host-guest chemistry of dendrimer/guest complexes and may play important roles in the study of dendrimer/DNA aggregates by a "bottom-up" strategy.

  8. Transport of surface engineered polyamidoamine (PAMAM) dendrimers across IPEC-J2 cell monolayers.

    Science.gov (United States)

    Pisal, Dipak S; Yellepeddi, Venkata K; Kumar, Ajay; Palakurthi, Srinath

    2008-11-01

    The aim of our study was to prepare arginine-and ornithine-conjugated Polyamidoamine (PAMAM) dendrimers and study their permeability across IPEC-J2 cell monolayers, a new intestinal cell line model for drug absorption studies. Arginine and ornithine were conjugated to the amine terminals of the PAMAM(G4) dendrimers by Fmoc synthesis. The apical-to-basolateral (AB) and basolateral-to-apical (BA) apparent permeability coefficients (P(app)) for the PAMAM dendrimers increased by conjugating the dendrimers with both of these polyamines. The enhancement in permeability was dependent on the dendrimer concentration and duration of incubation. Correlation between monolayer permeability and the decrease in transepithelial electrical resistance (TEER) with the PAMAM dendrimers and the polyamine-conjugated dendrimers suggests that paracellular transport is one of the mechanisms of transport across the epithelial cells. Cytotoxicity of these surface-modified dendrimers was evaluated in IPEC-J2 cells by MTT (methylthiazoletetrazolium) assay. Arginine-conjugated dendrimers were insignificantly more toxic than PAMAM dendrimer as well as ornithine-conjugated dendrimers. Though investigations on the possible involvement of other transport mechanisms are in progress, results of the present study suggest the potential of dendrimer-polyamine conjugates as the carriers for antigen/drug delivery through the oral mucosa.

  9. Molecular dynamic analysis of the structure of dendrimers

    Energy Technology Data Exchange (ETDEWEB)

    Canetta, E.; Maino, G. E-mail: maino@bologna.enea.it

    2004-01-01

    We present main results of molecular dynamics simulations that we have carried out in order to investigate structural properties of polyamidoamine (PAMAM) dendrimers. Obtained data confirm the PAMAM dendrimer structure proposed by experiments, performed by means of X-ray scattering (SAXS) and quasi-elastic light scattering (QELS) techniques.

  10. Molecular dynamic analysis of the structure of dendrimers

    International Nuclear Information System (INIS)

    Canetta, E.; Maino, G.

    2004-01-01

    We present main results of molecular dynamics simulations that we have carried out in order to investigate structural properties of polyamidoamine (PAMAM) dendrimers. Obtained data confirm the PAMAM dendrimer structure proposed by experiments, performed by means of X-ray scattering (SAXS) and quasi-elastic light scattering (QELS) techniques

  11. Dendrimers and Dendrons as Versatile Building Blocks for the Fabrication of Functional Hydrogels

    Directory of Open Access Journals (Sweden)

    Sadik Kaga

    2016-04-01

    Full Text Available Hydrogels have emerged as a versatile class of polymeric materials with a wide range of applications in biomedical sciences. The judicious choice of hydrogel precursors allows one to introduce the necessary attributes to these materials that dictate their performance towards intended applications. Traditionally, hydrogels were fabricated using either polymerization of monomers or through crosslinking of polymers. In recent years, dendrimers and dendrons have been employed as well-defined building blocks in these materials. The multivalent and multifunctional nature of dendritic constructs offers advantages in either formulation or the physical and chemical properties of the obtained hydrogels. This review highlights various approaches utilized for the fabrication of hydrogels using well-defined dendrimers, dendrons and their polymeric conjugates. Examples from recent literature are chosen to illustrate the wide variety of hydrogels that have been designed using dendrimer- and dendron-based building blocks for applications, such as sensing, drug delivery and tissue engineering.

  12. Some new aspects of dendrimer applications

    International Nuclear Information System (INIS)

    Flomenbom, Ophir; Amir, Roey J.; Shabat, Doron; Klafter, Joseph

    2005-01-01

    Dendrimers are characterized by special features that make them promising candidates for many applications. Here we focus on two such applications: dendrimers as light harvesting antennae, and dendrimers as molecular amplifiers, which may serve as novel platforms for drug delivery. Both applications stem from the unique structure of dendrimers. We present a theoretical framework based on the master equation within which we describe these applications. The quantities of interest are the first passage time (FPT), probability density function (PDF) and its moments. We examine how the FPT PDF and its characteristics depend on the geometric and energetic structures of the dendrimeric system. In particular, we investigate the dependence of the FPT properties on the number of generations (dendrimer size) and the system bias. We present analytical expressions for the FPT PDF for very efficient dendrimeric antennae and for dendrimeric amplifiers. For these cases the mean FPT scales linearly with the system length, and fluctuations around the mean FPT are negligible for large systems. Relationships of the FPT to light harvesting process for other types of system-bias are discussed

  13. Dendrimers as Potential Therapeutic Tools in HIV Inhibition

    Directory of Open Access Journals (Sweden)

    Xiangbo Li

    2013-07-01

    Full Text Available The present treatments for HIV transfection include chemical agents and gene therapies. Although many chemical drugs, peptides and genes have been developed for HIV inhibition, a variety of non-ignorable drawbacks limited the efficiency of these materials. In this review, we discuss the application of dendrimers as both therapeutic agents and non-viral vectors of chemical agents and genes for HIV treatment. On the one hand, dendrimers with functional end groups combine with the gp120 of HIV and CD4 molecule of host cell to suppress the attachment of HIV to the host cell. Some of the dendrimers are capable of intruding into the cell and interfere with the later stages of HIV replication as well. On the other hand, dendrimers are also able to transfer chemical drugs and genes into the host cells, which conspicuously increase the anti-HIV activity of these materials. Dendrimers as therapeutic tools provide a potential treatment for HIV infection.

  14. Dendrimers in Medicine

    DEFF Research Database (Denmark)

    Wu, Linping; Ficker, Mario; Christensen, Jørn Bolstad

    2015-01-01

    Dendrimers are three-dimensional macromolecular structures originating from a central core molecule and surrounded by successive addition of branching layers (generation). These structures exhibit a high degree of molecular uniformity, narrow molecular weight distribution, tunable size and shape ...

  15. Glycopeptide dendrimers. Part II

    Czech Academy of Sciences Publication Activity Database

    Niederhafner, Petr; Šebestík, Jaroslav; Ježek, Jan

    2008-01-01

    Roč. 14, č. 1 (2008), s. 44-65 ISSN 1075-2617 R&D Projects: GA ČR GA203/03/1362; GA ČR GA203/06/1272; GA MZe QF3115; GA AV ČR KAN200520703 Institutional research plan: CEZ:AV0Z40550506 Keywords : artificial virus * cascade-release dendrimers * glycopeptide dendrimers * glycoconjugate * glycopeptides Subject RIV: CC - Organic Chemistry Impact factor: 1.654, year: 2008

  16. Skin Delivery of EGCG and Silibinin: Potential of Peptide Dendrimers for Enhanced Skin Permeation and Deposition.

    Science.gov (United States)

    Shetty, Pallavi Krishna; Manikkath, Jyothsna; Tupally, Karnaker; Kokil, Ganesh; Hegde, Aswathi R; Raut, Sushil Y; Parekh, Harendra S; Mutalik, Srinivas

    2017-08-01

    The aim of the present study was to evaluate the ability of the peptide dendrimers to facilitate transdermal delivery of antioxidants, silibinin, and epigallocatechin-3-gallate (EGCG). Drug-peptide dendrimer complexes were prepared and evaluated for their ability to permeate across the skin. The data revealed the ready formation of complexes between drug and peptide dendrimer in a molar ratio of 1:1. In vitro permeation studies using excised rat skin and drug-peptide dendrimer complexes showed highest values for cumulative drug permeation at the end of 12 h (Q 12 ), with corresponding permeability coefficient (Kp) and enhancement ratio values also determined at this time point. With silibinin, 3.96-, 1.81-, and 1.06-fold increase in skin permeation was observed from silibinin-peptide dendrimer complex, simultaneous application of silibinin + peptide dendrimer, and pretreatment of skin with peptide dendrimer, respectively, in comparison with passive diffusion. With EGCG, 9.82-, 2.04-, and 1.72-fold increase in skin permeation was observed from EGCG-peptide dendrimer complex, simultaneous application of EGCG + peptide dendrimer, and pretreatment of skin with peptide dendrimer, respectively, in comparison with passive diffusion. The present study demonstrates the application of peptide dendrimers in effectively delivering antioxidants such as EGCG and silibinin into the skin, thus offering the potential to provide antioxidant effects when delivered via appropriately formulated topical preparations.

  17. Impact of Dendrimer Terminal Group Chemistry on Blockage of the Anthrax Toxin Channel: A Single Molecule Study.

    Science.gov (United States)

    Yamini, Goli; Kalu, Nnanya; Nestorovich, Ekaterina M

    2016-11-15

    Nearly all the cationic molecules tested so far have been shown to reversibly block K⁺ current through the cation-selective PA 63 channels of anthrax toxin in a wide nM-mM range of effective concentrations. A significant increase in channel-blocking activity of the cationic compounds was achieved when multiple copies of positively charged ligands were covalently linked to multivalent scaffolds, such as cyclodextrins and dendrimers. Even though multivalent binding can be strong when the individual bonds are relatively weak, for drug discovery purposes we often strive to design multivalent compounds with high individual functional group affinity toward the respective binding site on a multivalent target. Keeping this requirement in mind, here we perform a single-channel/single-molecule study to investigate kinetic parameters of anthrax toxin PA 63 channel blockage by second-generation (G2) poly(amido amine) (PAMAM) dendrimers functionalized with different surface ligands, including G2-NH₂, G2-OH, G2-succinamate, and G2-COONa. We found that the previously reported difference in IC 50 values of the G2-OH/PA 63 and G2-NH₂/PA 63 binding was determined by both on- and off-rates of the reversible dendrimer/channel binding reaction. In 1 M KCl, we observed a decrease of about three folds in k o n and a decrease of only about ten times in t r e s with G2-OH compared to G2-NH₂. At the same time for both blockers, k o n and t r e s increased dramatically with transmembrane voltage increase. PAMAM dendrimers functionalized with negatively charged succinamate, but not carboxyl surface groups, still had some residual activity in inhibiting the anthrax toxin channels. At 100 mV, the on-rate of the G2-succinamate binding was comparable with that of G2-OH but showed weaker voltage dependence when compared to G2-OH and G2-NH₂. The residence time of G2-succinamate in the channel exhibited opposite voltage dependence compared to G2-OH and G2-NH₂, increasing with the cis

  18. Structure of Carbon Nanotube-dendrimer composite

    OpenAIRE

    Vasumathi, V.; Pramanik, Debabrata; Sood, A. K.; Maiti, Prabal K

    2012-01-01

    Using all atomistic molecular dynamics (MD) simulations we report the microscopic picture of the nanotube-dendrimer complex for PAMAM dendrimer of generation 2 to 4 and carbon nanotube of chirality (6,5). We find compact wrapping conformations of dendrimer onto the nanotube surface for all the three generations of PAMAM dendrimer. The degree of wrapping is more for non-protonated dendrimer compared to the protonated dendrimer. For comparison we also study the interaction of another dendrimer,...

  19. Transport and biodistribution of dendrimers across human fetal membranes: implications for intravaginal administration of dendrimer-drug conjugates.

    Science.gov (United States)

    Menjoge, Anupa R; Navath, Raghavendra S; Asad, Abbas; Kannan, Sujatha; Kim, Chong J; Romero, Roberto; Kannan, Rangaramanujam M

    2010-06-01

    Dendrimers are emerging as promising topical antimicrobial agents, and as targeted nanoscale drug delivery vehicles. Topical intravaginal antimicrobial agents are prescribed to treat the ascending genital infections in pregnant women. The fetal membranes separate the extra-amniotic space and fetus. The purpose of the study is to determine if the dendrimers can be selectively used for local intravaginal application to pregnant women without crossing the membranes into the fetus. In the present study, the transport and permeability of PAMAM (poly (amidoamine)) dendrimers, across human fetal membrane (using a side by side diffusion chamber), and its biodistribution (using immunofluorescence) are evaluated ex-vivo. Transport across human fetal membranes (from the maternal side) was evaluated using Fluorescein (FITC), an established transplacental marker (positive control, size approximately 400 Da) and fluorophore-tagged G(4)-PAMAM dendrimers (approximately 16 kDa). The fluorophore-tagged G(4)-PAMAM dendrimers were synthesized and characterized using (1)H NMR, MALDI TOF MS and HPLC analysis. Transfer was measured across the intact fetal membrane (chorioamnion), and the separated chorion and amnion layers. Over a 5 h period, the dendrimer transport across all the three membranes was less than dendrimer (5.8 x 10(-8) cm(2)/s). The biodistribution showed that the dendrimers were largely present in interstitial spaces in the decidual stromal cells and the chorionic trophoblast cells (in 2.5-4 h) and surprisingly, to a smaller extent internalized in nuclei of trophoblast cells and nuclei and cytoplasm of stromal cells. Passive diffusion and paracellular transport appear to be the major route for dendrimer transport. The overall findings further suggest that entry of drugs conjugated to dendrimers would be restricted across the human fetal membranes when administered topically by intravaginal route, suggesting new ways of selectively delivering therapeutics to the mother

  20. Transport and Biodistribution of Dendrimers Across Human Fetal Membranes: Implications for Intravaginal Administration of Dendrimers

    Science.gov (United States)

    Menjoge, Anupa R.; Navath, Raghavendra S.; Asad, Abbas; Kannan, Sujatha; Kim, Chong Jai; Romero, Roberto; Kannan, Rangaramanujam M.

    2010-01-01

    Dendrimers are emerging as promising topical antimicrobial agents, and as targeted nanoscale drug delivery vehicles. Topical intravaginal antimicrobial agents are prescribed to treat the ascending genital infections in pregnant women. The fetal membranes separate the extra-amniotic space and fetus. The purpose of the study is to determine if the dendrimers can be selectively used for local intravaginal application to pregnant women without crossing the membranes into the fetus. In the present study, the transport and permeability of PAMAM (poly(amidoamine)) dendrimers, across human fetal membrane (using a side-by-side diffusion chamber), and its biodistribution (using immunofluorescence) are evaluated ex-vivo. Transport across human fetal membranes (from the maternal side) was evaluated using Fluorescein (FITC), an established transplacental marker (positive control, size~ 400 Da) and fluorophore-tagged G4-PAMAM dendrimers (~ 16 kDa). The fluorophore-tagged G4-PAMAM dendrimers were synthesized and characterized using 1H NMR, MALDI TOF-MS and HPLC analysis. Transfer was measured across the intact fetal membrane (chorioamnion), and the separated chorion and amnion layers. Over a five hour period, the dendrimer transport across all the three membranes was less than transport of FITC was relatively fast with as much as 49% transport across the amnion. The permeability of FITC (7.9 × 10-7 cm2/s) through the chorioamnion was 7-fold higher than that of the dendrimer (5.8 × 10-8 cm2/s). The biodistribution showed that the dendrimers were largely present in interstitial spaces in the decidual stromal cells and the chorionic trophoblast cells (in 2.5 to 4 h) and surprisingly, to a smaller extent internalized in nuclei of trophoblast cells and nuclei and cytoplasm of stromal cells. Passive diffusion and paracellular transport appear to be the major route for dendrimer transport. The overall findings further suggest that entry of drugs conjugated to dendrimers would be

  1. Preclinical studies of dendrimer prodrugs.

    Science.gov (United States)

    Kojima, Chie

    2015-01-01

    Dendrimers are synthetic macromolecules with well-defined structures bearing a wide variety of functional groups on their periphery. These groups can be used to conjugate bioactive molecules such as drugs, ligands and imaging agents. Dendrimer prodrugs can be used to improve the water solubility and pharmacokinetic properties of the corresponding free drugs. This article summarizes preclinical studies pertaining to the use of drug-dendrimer conjugates as dendrimer prodrugs for the treatments of various diseases, including cancer and inflammatory diseases. A wide range of anticancer drugs have been conjugated to dendrimers via biodegradable linkers. The side effects of the parent drugs can be markedly reduced using dendrimer prodrugs, with some drugs showing improved efficacy. Anti-inflammatory agents have also been conjugated to dendrimers and used to treat a number of inflammatory diseases. Drug-dendrimer conjugates are preferable to drug-dendrimer complexes, where the use of degradable linkers is critical to the release of the drug. Polyethylene glycol and/or ligands can be added to a dendrimer prodrug, which is useful for the targeting of affected tissues. Imaging probes can also be incorporated into dendrimer prodrugs for the simultaneous delivery of therapeutic and diagnostic agents as 'theranostics.'

  2. Dendrimers as Carriers for siRNA Delivery and Gene Silencing: A Review

    Directory of Open Access Journals (Sweden)

    Jiangyu Wu

    2013-01-01

    Full Text Available RNA interference (RNAi was first literaturally reported in 1998 and has become rapidly a promising tool for therapeutic applications in gene therapy. In a typical RNAi process, small interfering RNAs (siRNA are used to specifically downregulate the expression of the targeted gene, known as the term “gene silencing.” One key point for successful gene silencing is to employ a safe and efficient siRNA delivery system. In this context, dendrimers are emerging as potential nonviral vectors to deliver siRNA for RNAi purpose. Dendrimers have attracted intense interest since their emanating research in the 1980s and are extensively studied as efficient DNA delivery vectors in gene transfer applications, due to their unique features based on the well-defined and multivalent structures. Knowing that DNA and RNA possess a similar structure in terms of nucleic acid framework and the electronegative nature, one can also use the excellent DNA delivery properties of dendrimers to develop effective siRNA delivery systems. In this review, the development of dendrimer-based siRNA delivery vectors is summarized, focusing on the vector features (siRNA delivery efficiency, cytotoxicity, etc. of different types of dendrimers and the related investigations on structure-activity relationship to promote safe and efficient siRNA delivery system.

  3. Dendrimers as Carriers for siRNA Delivery and Gene Silencing: A Review

    Science.gov (United States)

    Huang, Weizhe; He, Ziying

    2013-01-01

    RNA interference (RNAi) was first literaturally reported in 1998 and has become rapidly a promising tool for therapeutic applications in gene therapy. In a typical RNAi process, small interfering RNAs (siRNA) are used to specifically downregulate the expression of the targeted gene, known as the term “gene silencing.” One key point for successful gene silencing is to employ a safe and efficient siRNA delivery system. In this context, dendrimers are emerging as potential nonviral vectors to deliver siRNA for RNAi purpose. Dendrimers have attracted intense interest since their emanating research in the 1980s and are extensively studied as efficient DNA delivery vectors in gene transfer applications, due to their unique features based on the well-defined and multivalent structures. Knowing that DNA and RNA possess a similar structure in terms of nucleic acid framework and the electronegative nature, one can also use the excellent DNA delivery properties of dendrimers to develop effective siRNA delivery systems. In this review, the development of dendrimer-based siRNA delivery vectors is summarized, focusing on the vector features (siRNA delivery efficiency, cytotoxicity, etc.) of different types of dendrimers and the related investigations on structure-activity relationship to promote safe and efficient siRNA delivery system. PMID:24288498

  4. Fluorophore:dendrimer ratio impacts cellular uptake and intracellular fluorescence lifetime.

    Science.gov (United States)

    Dougherty, Casey A; Vaidyanathan, Sriram; Orr, Bradford G; Banaszak Holl, Mark M

    2015-02-18

    G5-NH2-TAMRAn (n = 1-4, 5+, and 1.5(avg)) were prepared with n = 1-4 as a precise dye:dendrimer ratio, 5+ as a mixture of dendrimers with 5 or more dye per dendrimer, and 1.5(avg) as a Poisson distribution of dye:dendrimer ratios with a mean of 1.5 dye per dendrimer. The absorption intensity increased sublinearly with n whereas the fluorescence emission and lifetime decreased with an increasing number of dyes per dendrimer. Flow cytometry was employed to quantify uptake into HEK293A cells. Dendrimers with 2-4 dyes were found to have greater uptake than dendrimer with a single dye. Fluorescence lifetime imaging microscopy (FLIM) showed that the different dye:dendrimer ratio alone was sufficient to change the fluorescence lifetime of the material observed inside cells. We also observed that the lifetime of G5-NH2-TAMRA5+ increased when present in the cell as compared to solution. However, cells treated with G5-NH2-TAMRA1.5(avg) did not exhibit the high lifetime components present in G5-NH2-TAMRA1 and G5-NH2-TAMRA5+. In general, the effects of the dye:dendrimer ratio on fluorescence lifetime were of similar magnitude to environmentally induced lifetime shifts.

  5. Viologen-Phosphorus Dendrimers Inhibit α-Synuclein Fibrillation.

    Science.gov (United States)

    Milowska, Katarzyna; Grochowina, Justyna; Katir, Nadia; El Kadib, Abdelkrim; Majoral, Jean-Pierre; Bryszewska, Maria; Gabryelak, Teresa

    2013-03-04

    Inhibition of α-synuclein (ASN) fibril formation is a potential therapeutic strategy in Parkinson's disease and other synucleinopathies. The aim of this study was to examine the role of viologen-phosphorus dendrimers in the α-synuclein fibrillation process and to assess the structural changes in α-synuclein under the influence of dendrimers. ASN interactions with phosphonate and pegylated surface-reactive viologen-phosphorus dendrimers were examined by measuring the zeta potential, which allowed determining the number of dendrimer molecules that bind to the ASN molecule. The fibrillation kinetics and the structural changes were examined using ThT fluorescence and CD spectroscopy. Depending on the concentration of the used dendrimer and the nature of the reactive groups located on the surface, ASN fibrillation kinetics can be significantly reduced, and even, in the specific case of phosphonate dendrimers, the fibrillation can be totally inhibited at low concentrations. The presented results indicate that viologen-phosphorus dendrimers are able to inhibit ASN fibril formation and may be used as fibrillar regulating agents in neurodegenerative disorders.

  6. Host-guest chemistry of dendrimer-drug complexes: 7. Formation of stable inclusions between acetylated dendrimers and drugs bearing multiple charges.

    Science.gov (United States)

    Fang, Min; Zhang, Jiahai; Wu, Qinglin; Xu, Tongwen; Cheng, Yiyun

    2012-03-15

    Drug molecules bearing multiple charges usually form precipitates with cationic dendrimers, which presents a challenge during the preparation of dendrimer inclusions for these drugs. In the present study, fully acetylated polyamidoamine (PAMAM) dendrimers were proposed as stable vehicles for drug molecules bearing two negative charges such as Congo red and indocyanine green. NMR techniques including (1)H NMR and (1)H-(1)H NOESY were used to characterize the host-guest chemistry of acetylated dendrimer and these guest molecules. The cationic PAMAM dendrimer was found to form a precipitate with Congo red and indocyanine green, but the acetylated one avoided the formation of cross-linking structures in aqueous solutions. NOESY studies revealed the encapsulation of Congo red and indocyanine green within the interior cavities of PAMAM dendrimers at mild acidic conditions and acetylated dendrimers show much stronger ability to encapsulate the guest molecules than cationic ones. Also, UV-vis-NIR studies suggest that acetylated dendrimers significantly improve the photostability of indocyanine green and prevent the formation of indocyanine green J-aggregates in aqueous solutions. The present study provides a new insight into dendrimer-based host-guest systems, especially for those guest molecules bearing multiple charges. © 2012 American Chemical Society

  7. Continuous-time quantum walks on multilayer dendrimer networks

    Science.gov (United States)

    Galiceanu, Mircea; Strunz, Walter T.

    2016-08-01

    We consider continuous-time quantum walks (CTQWs) on multilayer dendrimer networks (MDs) and their application to quantum transport. A detailed study of properties of CTQWs is presented and transport efficiency is determined in terms of the exact and average return probabilities. The latter depends only on the eigenvalues of the connectivity matrix, which even for very large structures allows a complete analytical solution for this particular choice of network. In the case of MDs we observe an interplay between strong localization effects, due to the dendrimer topology, and good efficiency from the linear segments. We show that quantum transport is enhanced by interconnecting more layers of dendrimers.

  8. Poly (amidoamine) dendrimer-mediated hybrid formulation for combination therapy of ramipril and hydrochlorothiazide.

    Science.gov (United States)

    Singh, Mayank Kumar; Pooja, Deep; Kulhari, Hitesh; Jain, Sanjay Kumar; Sistla, Ramakrishna; Chauhan, Abhay Singh

    2017-01-01

    We present a dendrimer-based hybrid formulation strategy to explore the potential of poly (amidoamine) PAMAM dendrimers to be used as drug carriers for combination therapy of an anti-hypertensive drug ramipril (RAPL) and a diuretic hydrochlorothiazide (HCTZ). The drug-dendrimer complexes were prepared by phase-equilibration method. The results showed that the solubility of RAPL and HCTZ was dependent on dendrimer concentration and pH of dendrimer solution. The solubility profile of both RAPL and HCTZ dendrimer complexes illustrated a non-linear relationship with dendrimer concentration. At 0.8% (w/v) dendrimer concentration, solubility of RAPL was increased 4.91 folds with amine-terminated while for HCTZ, solubility enhancement was highest (3.72 folds) with carboxy-terminated. The complexes were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance analysis and high performance liquid chromatography. In-vitro drug dissolution performance of pure drugs, individual drug loaded dendrimer formulations and hybrid formulations was studied in USP dissolution medium (pH7.0) and in simulated gastric fluid (pH1.2). Dendrimer mediated formulations showed faster and complete dissolution compared to pure RAPL or HCTZ. Surprisingly, similar pattern of dissolution profile was established with hybrid formulations as compared to individual drug loaded dendrimers. The dendrimer-based hybrid formulations were found to be stable at dark and refrigerated conditions up to 5weeks. Conclusively, the proposed formulation strategy establishes a novel multitasking platform using dendrimer for simultaneous loading and delivery of multiple drugs for pharmaceutical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Understanding the Structure-Function Relationships of Dendrimers in Environmental and Biomedical Applications

    Science.gov (United States)

    Wang, Bo

    We are living an era wherein nanoparticles (NPs) have been widely applied in our lives. Dendrimers are special polymeric NPs with unique physiochemical properties, which have been intensely explored for a variety of applications. Current studies on dendrimers are bottlenecked by insufficient understandings of their structure and dynamic behaviors from a molecular level. With primarily computational approaches supplemented by many other experimental technics, this dissertation aims to establish structure-function relationships of dendrimers in environmental and biomedical applications. More specifically, it thoroughly investigates the interactions between dendrimers and different biomolecules including carbon-based NPs, metal-based NPs, and proteins/peptides. Those results not only provide profound knowledge for evaluating the impacts of dendrimers on environmental and biological systems but also facilitate designing next-generation functional polymeric nanomaterials. The dissertation is organized as following. Chapter 1 provides an overview of current progresses on dendrimer studies, where methodology of Discrete Molecular Dynamics (DMD), my major research tool, is also introduced. Two directions of utilizing dendrimers will be discussed in following chapters. Chapter 2 will focus on environmental applications of dendrimers, where two back-to-back studies are presented. I will start from describing some interesting observations from experiments i.e. dendrimers dispersed model oil molecules. Then, I will reveal why surface chemistries of dendrimers lead to different remediation efficiencies by computational modelings. Finally, I will demonstrate different scenarios of dendrimer-small molecules association. Chapter 3 is centered on dendrimers in the biomedical applications including two subtopics. In the first topic, we will discuss dendrimers as surfactants that modulating the interactions between proteins and NPs. Some fundamental concepts regarding to NPs

  10. Influence of dendrimer's structure on its activity against amyloid fibril formation

    International Nuclear Information System (INIS)

    Klajnert, B.; Cortijo-Arellano, M.; Cladera, J.; Bryszewska, M.

    2006-01-01

    Inhibition of fibril assembly is a potential therapeutic strategy in neurodegenerative disorders such as prion and Alzheimer's diseases. Highly branched, globular polymers-dendrimers-are novel promising inhibitors of fibril formation. In this study, the effect of polyamidoamine (PAMAM) dendrimers (generations 3rd, 4th, and 5th) on amyloid aggregation of the prion peptide PrP 185-208 and the Alzheimer's peptide Aβ 1-28 was examined. Amyloid fibrils were produced in vitro and their formation was monitored using the dye thioflavin T (ThT). Fluorescence studies were complemented with electron microscopy. The results show that the higher the dendrimer generation, the larger the degree of inhibition of the amyloid aggregation process and the more effective are dendrimers in disrupting the already existing fibrils. A hypothesis on dendrimer-peptide interaction mechanism is presented based on the dendrimers' molecular structure

  11. Dendrimers: new hope for cancer

    International Nuclear Information System (INIS)

    Ghosh, S.S.

    2010-01-01

    A class of nanomaterials called dendrimers have been found particularly useful in cancer treatment. Dendrimers have often been referred to as the Polymers of the 21st century. The name Dendrimer comes from the Greek dendron, meaning tree. They are nearly perfect monodisperse (a consistent size and form) macromolecules with a regular and highly branched three-dimensional architecture having an average size of around 5x10 -9 m, which can be artificially synthesized

  12. Tecto-dendrimers: a study of covalently bound nanospheres

    Energy Technology Data Exchange (ETDEWEB)

    Welch, Paul M [Los Alamos National Laboratory; Welch, Cynthia F [Los Alamos National Laboratory

    2008-01-01

    We present a computational and theoretical study of the size, shape, and solution properties of tecto-dendrimers. This class of polymer, composed of a central dendrimer with multiple dendrimers attached at its periphery, holds promise for multi-drug delivery and environmental remediation applications. We find (i) that the maximum number of tecto-units that may be attached to the central core varies logarightmically with the ratio of the sizes of the dendrimers, (ii) that their density profiles display a minimum near the junction of the tecto-units with the core, (iii) that a simple expression captures their radius of gyration, (iv) that their intrinsic viscosity will display a maximum as a function of the number of tecto-units attached, and (v) that their sphericity increases with increasing number of attached tecto-units. These results should bear upon both the synthesis and application of these materials.

  13. Exciton confinement in organic dendrimer quantum wells for opto-electronic applications

    Science.gov (United States)

    Lupton, J. M.; Samuel, I. D. W.; Burn, P. L.; Mukamel, S.

    2002-01-01

    Organic dendrimers are a fascinating new class of materials for opto-electronic applications. We present coupled electronic oscillator calculations on novel nanoscale conjugated dendrimers for use in organic light-emitting diodes. Strong confinement of excitations at the center of the dendrimers is observed, which accounts for the dependence of intermolecular interactions and charge transport on the degree of branching of the dendrimer. The calculated absorption spectra are in excellent agreement with the measured data and show that benzene rings are shared between excitations on the linear segments of the hyperbranched molecules. The coupled electronic oscillator approach is ideally suited to treat large dendritic molecules.

  14. 64Cu-Labeled LyP-1-Dendrimer for PET-CT Imaging of Atherosclerotic Plaque

    Science.gov (United States)

    2015-01-01

    The ability to detect and quantify macrophage accumulation can provide important diagnostic and prognostic information for atherosclerotic plaque. We have previously shown that LyP-1, a cyclic 9-amino acid peptide, binds to p32 proteins on activated macrophages, facilitating the visualization of atherosclerotic plaque with PET. Yet, the in vivo plaque accumulation of monomeric [18F]FBA-LyP-1 was low (0.31 ± 0.05%ID/g). To increase the avidity of LyP-1 constructs to p32, we synthesized a dendritic form of LyP-1 on solid phase using lysine as the core structural element. Imaging probes (FAM or 6-BAT) were conjugated to a lysine or cysteine on the dendrimer for optical and PET studies. The N-terminus of the dendrimer was further modified with an aminooxy group in order to conjugate LyP-1 and ARAL peptides bearing a ketone. Oxime ligation of peptides to both dendrimers resulted in (LyP-1)4- and (ARAL)4-dendrimers with optical (FAM) and PET probes (6-BAT). For PET-CT studies, (LyP-1)4- and (ARAL)4-dendrimer-6-BAT were labeled with 64Cu (t1/2 = 12.7 h) and intravenously injected into the atherosclerotic (ApoE–/–) mice. After two hours of circulation, PET-CT coregistered images demonstrated greater uptake of the (LyP-1)4-dendrimer-64Cu than the (ARAL)4-dendrimer-64Cu in the aortic root and descending aorta. Ex vivo images and the biodistribution acquired at three hours after injection also demonstrated a significantly higher uptake of the (LyP-1)4-dendrimer-64Cu (1.1 ± 0.26%ID/g) than the (ARAL)4-dendrimer-64Cu (0.22 ± 0.05%ID/g) in the aorta. Similarly, subcutaneous injection of the LyP-1-dendrimeric carriers resulted in preferential accumulation in plaque-containing regions over 24 h. In the same model system, ex vivo fluorescence images within aortic plaque depict an increased accumulation and penetration of the (LyP-1)4-dendrimer-FAM as compared to the (ARAL)4-dendrimer-FAM. Taken together, the results suggest that the (LyP-1)4-dendrimer can be applied for in

  15. Dendrimer-protein interactions versus dendrimer-based nanomedicine.

    Science.gov (United States)

    Shcharbin, Dzmitry; Shcharbina, Natallia; Dzmitruk, Volha; Pedziwiatr-Werbicka, Elzbieta; Ionov, Maksim; Mignani, Serge; de la Mata, F Javier; Gómez, Rafael; Muñoz-Fernández, Maria Angeles; Majoral, Jean-Pierre; Bryszewska, Maria

    2017-04-01

    Dendrimers are hyperbranched polymers belonging to the huge class of nanomedical devices. Their wide application in biology and medicine requires understanding of the fundamental mechanisms of their interactions with biological systems. Summarizing, electrostatic force plays the predominant role in dendrimer-protein interactions, especially with charged dendrimers. Other kinds of interactions have been proven, such as H-bonding, van der Waals forces, and even hydrophobic interactions. These interactions depend on the characteristics of both participants: flexibility and surface charge of a dendrimer, rigidity of protein structure and the localization of charged amino acids at its surface. pH and ionic strength of solutions can significantly modulate interactions. Ligands and cofactors attached to a protein can also change dendrimer-protein interactions. Binding of dendrimers to a protein can change its secondary structure, conformation, intramolecular mobility and functional activity. However, this strongly depends on rigidity versus flexibility of a protein's structure. In addition, the potential applications of dendrimers to nanomedicine are reviwed related to dendrimer-protein interactions. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Peptide- and saccharide-conjugated dendrimers for targeted drug delivery: a concise review

    Science.gov (United States)

    Liu, Jie; Gray, Warren D.; Davis, Michael E.; Luo, Ying

    2012-01-01

    Dendrimers comprise a category of branched materials with diverse functions that can be constructed with defined architectural and chemical structures. When decorated with bioactive ligands made of peptides and saccharides through peripheral chemical groups, dendrimer conjugates are turned into nanomaterials possessing attractive binding properties with the cognate receptors. At the cellular level, bioactive dendrimer conjugates can interact with cells with avidity and selectivity, and this function has particularly stimulated interests in investigating the targeting potential of dendrimer materials for the design of drug delivery systems. In addition, bioactive dendrimer conjugates have so far been studied for their versatile capabilities to enhance stability, solubility and absorption of various types of therapeutics. This review presents a brief discussion on three aspects of the recent studies to use peptide- and saccharide-conjugated dendrimers for drug delivery: (i) synthesis methods, (ii) cell- and tissue-targeting properties and (iii) applications of conjugated dendrimers in drug delivery nanodevices. With more studies to elucidate the structure–function relationship of ligand–dendrimer conjugates in transporting drugs, the conjugated dendrimers hold promise to facilitate targeted delivery and improve drug efficacy for discovery and development of modern pharmaceutics. PMID:23741608

  17. Computer simulations of dendrimer-polyelectrolyte complexes.

    Science.gov (United States)

    Pandav, Gunja; Ganesan, Venkat

    2014-08-28

    We carry out a systematic analysis of static properties of the clusters formed by complexation between charged dendrimers and linear polyelectrolyte (LPE) chains in a dilute solution under good solvent conditions. We use single chain in mean-field simulations and analyze the structure of the clusters through radial distribution functions of the dendrimer, cluster size, and charge distributions. The effects of LPE length, charge ratio between LPE and dendrimer, the influence of salt concentration, and the dendrimer generation number are examined. Systems with short LPEs showed a reduced propensity for aggregation with dendrimers, leading to formation of smaller clusters. In contrast, larger dendrimers and longer LPEs lead to larger clusters with significant bridging. Increasing salt concentration was seen to reduce aggregation between dendrimers as a result of screening of electrostatic interactions. Generally, maximum complexation was observed in systems with an equal amount of net dendrimer and LPE charges, whereas either excess LPE or dendrimer concentrations resulted in reduced clustering between dendrimers.

  18. Bioconjugation strategies for multivalent peptide ligands

    NARCIS (Netherlands)

    Lempens, E.H.M.

    2011-01-01

    In nature multiple weak interactions are often combined to enhance the overall affinity and specificity of binding. This effect is known as multivalency and plays a pivotal role in e.g. adhesion of viruses or bacteria to cells, immune responses and protein-protein interactions. Inspired by nature’s

  19. Structure-skin permeability relationship of dendrimers.

    Science.gov (United States)

    Venuganti, Venkata Vamsi; Sahdev, Preety; Hildreth, Michael; Guan, Xiangming; Perumal, Omathanu

    2011-09-01

    To investigate skin penetration of poly (amidoamine) (PAMAM) dendrimers as a function of surface charge and molecular weight in presence and absence of iontophoresis. Dendrimers were labeled with fluoroisothiocynate (FITC); skin penetration of dendrimers was studied using excised porcine skin in-vitro. Skin penetration of FITC-labeled dendrimers was quantified using confocal laser scanning microscope (CLSM). G2-G6 NH(2), G3.5-COOH and G4-OH dendrimers were used. Cationic dendrimers showed higher skin penetration than neutral and anionic dendrimers. Skin penetration of cationic dendrimer increased linearly with increase in treatment time. Iontophoresis enhanced skin penetration of cationic and neutral dendrimers. Increase in current strength and current duration increased skin transport of dendrimers. Passive and iontophoretic skin penetration of cationic dendrimers was inversely related to their molecular weight. Dendrimer penetrated the skin through intercellular lipids and hair follicles. With iontophoresis, dendrimer was also found in localized skin regions. The study demonstrates that the physicochemical properties of dendrimers influence their skin transport. Findings can be used to design dendrimer-based nanocarriers for drug delivery to skin.

  20. Design of water-soluble, thiol-reactive polymers of controlled molecular weight: a novel multivalent scaffold

    Science.gov (United States)

    Carrillo, Alvaro; Gujraty, Kunal V.; Rai, Prakash R.; Kane, Ravi S.

    2005-07-01

    Multivalent molecules, i.e. scaffolds presenting multiple copies of a suitable ligand, constitute an emerging class of nanoscale therapeutics. We present a novel approach for the design of multivalent ligands, which allows the biofunctionalization of polymers with proteins or peptides in a controlled orientation. It consists of the synthesis of water-soluble, activated polymer scaffolds of controlled molecular weight, which can be biofunctionalized with various thiolated ligands in aqueous media under mild conditions. These polymers were synthesized by ring-opening metathesis polymerization (ROMP) and further modified to make them water-soluble. The incorporation of chloride groups activated the polymers to react with thiol-containing peptides or proteins, and the formation of multivalent ligands in aqueous media was demonstrated. This strategy represents a convenient route for synthesizing multivalent ligands of controlled dimensions and valency.

  1. Optical absorption in compact and extended dendrimers

    International Nuclear Information System (INIS)

    Supritz, C.; Engelmann, A.; Reineker, P.

    2005-01-01

    Dendrimers are highly branched molecules, which are expected to be useful, for example, as efficient artificial light harvesting systems, in nano-technological or in medical applications. There are two different classes of dendrimers: compact dendrimers with constant distance between neighboring branching points throughout the macromolecule and extended dendrimers, where this distance increases from the system periphery to the center. We investigate the linear optical absorption spectra of these dendrimer types using the Frenkel exciton concept. The electron-phonon interaction is taken into account by introducing a heat bath that interacts with the exciton in a stochastic manner. We discuss compact dendrimers with equal excitation energies at all molecules, dendrimers with a functionalized core as well as with a whole branch functionalized. Furthermore the line shape of a compact dendrimer is discussed when neighboring molecules at the periphery interact and when all molecules have randomly distributed excitation energies due to disorder. Finally, we discuss two models for extended dendrimers

  2. Comparative toxicological assessment of PAMAM and thiophosphoryl dendrimers using embryonic zebrafish

    Directory of Open Access Journals (Sweden)

    Pryor JB

    2014-04-01

    Full Text Available Joseph B Pryor,1 Bryan J Harper,1 Stacey L Harper1,21Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, USA; 2School of Chemical, Biological, and Environmental Engineering, Oregon State University, Corvallis, OR, USAAbstract: Dendrimers are well-defined, polymeric nanomaterials currently being investigated for biomedical applications such as medical imaging, gene therapy, and tissue targeted therapy. Initially, higher generation (size dendrimers were of interest because of their drug carrying capacity. However, increased generation was associated with increased toxicity. The majority of studies exploring dendrimer toxicity have focused on a small range of materials using cell culture methods, with few studies investigating the toxicity across a wide range of materials in vivo. The objective of the present study was to investigate the role of surface charge and generation in dendrimer toxicity using embryonic zebrafish (Danio rerio as a model vertebrate. Due to the generational and charge effects observed at the cellular level, higher generation cationic dendrimers were hypothesized to be more toxic than lower generation anionic or neutral dendrimers with the same core composition. Polyamidoamine (PAMAM dendrimers elicited significant morbidity and mortality as generation was decreased. No significant adverse effects were observed from the suite of thiophosphoryl dendrimers studied. Exposure to ≥50 ppm cationic PAMAM dendrimers G3-amine, G4-amine, G5-amine, and G6-amine caused 100% mortality by 24 hours post-fertilization. Cationic PAMAM G6-amine at 250 ppm was found to be statistically more toxic than both neutral PAMAM G6-amidoethanol and anionic PAMAM G6-succinamic acid at the same concentration. The toxicity observed within the suite of varying dendrimers provides evidence that surface charge may be the best indicator of dendrimer toxicity. Dendrimer class and generation are other potential

  3. Predicting hydration energies for multivalent ions

    DEFF Research Database (Denmark)

    Andersson, Martin Peter; Stipp, Susan Louise Svane

    2014-01-01

    We have predicted the free energy of hydration for 40 monovalent and multivalent cations and anions using density functional theory and the implicit solvent model COnductor like Screening MOdel for Real Solvents (COSMO-RS) at the Becke-Perdew (BP)/Triple zeta valence with polarization functions...... (TZVP) level. Agreement with experimental data for monovalent and divalent ions is good and shows no significant systematic errors. Predictions are noticeably better than with standard COSMO. The agreement with experimental data for trivalent and tetravalent ions is slightly worse and shows systematic...... errors. Our results indicate that quantum chemical calculations combined with COSMO-RS solvent treatment is a reliable method for treating multivalent ions in solution, provided one hydration shell of explicit water molecules is included for metal cations. The accuracy is not high enough to allow...

  4. Poly(Propylene Imine Dendrimers and Amoxicillin as Dual-Action Antibacterial Agents

    Directory of Open Access Journals (Sweden)

    Natalia Wrońska

    2015-10-01

    Full Text Available Besides acting as antimicrobial compounds, dendrimers can be considered as agents that improve the therapeutic effectiveness of existing antibiotics. In this work we present a new approach to using amoxicillin (AMX against reference strains of common Gram-negative pathogens, alone and in combination with poly(propylene imine (PPI dendrimers, or derivatives thereof, in which 100% of the available hydrogen atoms are substituted with maltose (PPI 100%malG3. The concentrations of dendrimers used remained in the range non-toxic to eukaryotic cells. The results indicate that PPI dendrimers significantly enhance the antibacterial effect of amoxicillin alone, allowing antibiotic doses to be reduced. It is important to reduce doses of amoxicillin because its widespread use in medicine could lead to the development of bacterial resistance and environmental pollution. This is the first report on the combined antibacterial activity of PPI surface-modified maltose dendrimers and amoxicillin.

  5. Synthesis and biological evaluation of boronated polyglycerol dendrimers as potential agent for neutron capture therapy

    International Nuclear Information System (INIS)

    Silva, Gerald S.; Camillo, Maria A.P.; Higa, Olga Z.; Pugliesi, Reynaldo; Fermamdes, Edson G.R.; Queiroz, Alvaro A.A. de

    2005-01-01

    In this work, the polyglycerol dendrimer (PGLD) generation 5 was used to obtain a boronated macromolecule for boron neutron capture therapy. The PGLD dendrimer was synthesized by the ring opening polymerization of deprotonated glycidol using polyglycerol as core functionality in a step-growth processes denominated divergent synthesis. The PGLD dendritic structure was confirmed by gel permeation chromatography, nuclear magnetic resonance ( 1 H-NMR, 13 C-NMR) and matrix assisted laser desorption/ionization techniques. The synthesized dendrimer presented low dispersion in molecular weights (M w /M n = 1.05) and a degree of branching of 0.82, which characterize the polymer dendritic structure. Quantitative neutron capture radiography was used to investigate the boron-10 enrichment of the polyglycerol dendrimer. The in vitro cytotoxicity to Chinese hamster ovary cells of 10 B-PGLD dendrimer indicate lower cytotoxicity, suggesting that the macromolecule is a biocompatible material. (author)

  6. Which Dendrimer to Attain the Desired Properties? Focus on Phosphorhydrazone Dendrimers.

    Science.gov (United States)

    Caminade, Anne-Marie; Majoral, Jean-Pierre

    2018-03-09

    Among the six Critical Nanoscale Design Parameters (CNDPs) proposed by Prof. Donald A. Tomalia, this review illustrates the influence of the sixth one, which concerns the elemental composition, on the properties of dendrimers. After a large introduction that summarizes different types of dendrimers that have been compared with PolyAMidoAMine (PAMAM) dendrimers, this review will focus on the properties of positively and negatively charged phosphorhydrazone (PPH) dendrimers, especially in the field of biology, compared with other types of dendrimers, in particular PAMAM dendrimers, as well as polypropyleneimine (PPI), carbosilane, and p-Lysine dendrimers.

  7. Which Dendrimer to Attain the Desired Properties? Focus on Phosphorhydrazone Dendrimers

    Directory of Open Access Journals (Sweden)

    Anne-Marie Caminade

    2018-03-01

    Full Text Available Among the six Critical Nanoscale Design Parameters (CNDPs proposed by Prof. Donald A. Tomalia, this review illustrates the influence of the sixth one, which concerns the elemental composition, on the properties of dendrimers. After a large introduction that summarizes different types of dendrimers that have been compared with PolyAMidoAMine (PAMAM dendrimers, this review will focus on the properties of positively and negatively charged phosphorhydrazone (PPH dendrimers, especially in the field of biology, compared with other types of dendrimers, in particular PAMAM dendrimers, as well as polypropyleneimine (PPI, carbosilane, and p-Lysine dendrimers.

  8. Atomic level insights into realistic molecular models of dendrimer-drug complexes through MD simulations

    Science.gov (United States)

    Jain, Vaibhav; Maiti, Prabal K.; Bharatam, Prasad V.

    2016-09-01

    Computational studies performed on dendrimer-drug complexes usually consider 1:1 stoichiometry, which is far from reality, since in experiments more number of drug molecules get encapsulated inside a dendrimer. In the present study, molecular dynamic (MD) simulations were implemented to characterize the more realistic molecular models of dendrimer-drug complexes (1:n stoichiometry) in order to understand the effect of high drug loading on the structural properties and also to unveil the atomistic level details. For this purpose, possible inclusion complexes of model drug Nateglinide (Ntg) (antidiabetic, belongs to Biopharmaceutics Classification System class II) with amine- and acetyl-terminated G4 poly(amidoamine) (G4 PAMAM(NH2) and G4 PAMAM(Ac)) dendrimers at neutral and low pH conditions are explored in this work. MD simulation analysis on dendrimer-drug complexes revealed that the drug encapsulation efficiency of G4 PAMAM(NH2) and G4 PAMAM(Ac) dendrimers at neutral pH was 6 and 5, respectively, while at low pH it was 12 and 13, respectively. Center-of-mass distance analysis showed that most of the drug molecules are located in the interior hydrophobic pockets of G4 PAMAM(NH2) at both the pH; while in the case of G4 PAMAM(Ac), most of them are distributed near to the surface at neutral pH and in the interior hydrophobic pockets at low pH. Structural properties such as radius of gyration, shape, radial density distribution, and solvent accessible surface area of dendrimer-drug complexes were also assessed and compared with that of the drug unloaded dendrimers. Further, binding energy calculations using molecular mechanics Poisson-Boltzmann surface area approach revealed that the location of drug molecules in the dendrimer is not the decisive factor for the higher and lower binding affinity of the complex, but the charged state of dendrimer and drug, intermolecular interactions, pH-induced conformational changes, and surface groups of dendrimer do play an

  9. Phosphorus dendrimers and photodynamic therapy. Spectroscopic studies on two dendrimer-photosensitizer complexes: Cationic phosphorus dendrimer with rose bengal and anionic phosphorus dendrimer with methylene blue.

    Science.gov (United States)

    Dabrzalska, Monika; Zablocka, Maria; Mignani, Serge; Majoral, Jean Pierre; Klajnert-Maculewicz, Barbara

    2015-08-15

    Dendrimers due to their unique architecture may play an important role in drug delivery systems including chemotherapy, gene therapy and recently, photodynamic therapy as well. We investigated two dendrimer-photosensitizer systems in context of potential use of these systems in photodynamic therapy. The mixtures of an anionic phosphorus dendrimer of the second generation and methylene blue were studied by UV-vis spectroscopy while that of a cationic phosphorus dendrimer (third generation) and rose bengal were investigated by spectrofluorimetric methods. Spectroscopic analysis of these two systems revealed the formation of dendrimer-photosensitizer complexes via electrostatic interactions as well as π stacking. The stoichiometry of the rose bengal-cationic dendrimer complex was estimated to be 7:1 and 9:1 for the methylene blue-anionic dendrimer complex. The results suggest that these polyanionic or polycationic phosphorus dendrimers can be promising candidates as carriers in photodynamic therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Preparation of Cu Nanoclusters within Dendrimer Templates

    National Research Council Canada - National Science Library

    Zhao, M

    1998-01-01

    ... (16-atom Cu cluster in G4 and 64-atom Cu cluster in G6 dendrimers). The clusters remain trapped within the dendrimers for extended periods of time, do not agglomerate, and do not precipitate. The clusters can also be oxidized to yield dendrimer-encapsulated Cu(2+).

  11. Understanding Peptide Dendrimer Interactions with Model Cell Membrane Mimics

    DEFF Research Database (Denmark)

    Lind, Tania Kjellerup

    few new drugs have been marketed over the last decades, making it impossible to keep pace with the disturbing levels of multi-drug resistant bacteria. Research in the area of novel drugs, which are less prone to induce resistance, and in-depth knowledge on their uptake mechanisms is thus of paramount...... fusion method, which presents improved means for studying drug-membrane interactions in the future. The interaction mechanism of a family of dendrimers was examined and in particular one dendrimer (BALY) was extensively studied by the combined use of quartz crystal microbalance, atomic force microscopy...

  12. Dynamics simulation of a π-conjugated light-harvesting dendrimer II: phenylene-based dendrimer (phDG2)

    International Nuclear Information System (INIS)

    Kodama, Yasunobu; Ishii, Soh; Ohno, Kaoru

    2009-01-01

    We investigate the light-harvesting property of a π-conjugated dendrimer, phenylene-based dendrimer (phDG2), by carrying out a semi-classical Ehrenfest dynamics simulation based on the time-dependent density functional theory. Similar to our previous study of star-shaped stilbenoid phthalocyanine (SSS1Pc), phDG2 shows electron and hole transfer from the periphery to the core through a π-conjugated network when an electron is selectively excited in the periphery. The one-way electron and hole transfer occurs more easily in dendrimers with planar structure than in those with steric hindrance because π-conjugation is well maintained in the planar structure. The present results explain recent experiments by Akai et al (2005 J. Lumin. 112 449).

  13. Positron annihilation study of polyphenylene dendrimers

    International Nuclear Information System (INIS)

    Marek, T.; Suevegh, K.; Vertes, A.; Ernst, A.; Bauer, R.; Weil, T.; Wiesler, U.; Klapper, M.; Muellen, K.

    2003-01-01

    The free volume of a series of rigid polyphenylene dendrimers was studied by positron lifetime spectroscopy and the experimental data were compared with results from molecular dynamics calculations. Contrary to dendrimers containing flexible repeat units rigid polyphenylene dendrimers proved to contain large stable 'inner' voids of a distinct size between their dendritic branches. The size of the 'inner' cavities increases with the size of the dendrimer. Due to these voids, polyphenylene dendrimers are potentially attractive with respect to the selective incorporation of guest molecules

  14. [Dendrimers in biomedical sciences and nanotechnology].

    Science.gov (United States)

    Sekowski, Szymon; Miłowska, Katarzyna; Gabryelak, Teresa

    2008-12-30

    Dendrimers are relatively new, hyper-branched polymers that have many interesting abilities. Dendrimers could be used, for example, as drug or gene carriers, contrast agents, sensors for different metal ions, and in developing innovation technology. These spherical polymers are also characterized by pharmacological activity against different bacterial and viral diseases. Dendrimers are currently being intensively investigated as anti-prion and anti-amyloid fibril agents. They can be used to build specific dendrimer films to be applied in modern technology. This review describes different uses of dendrimer particles in biomedical sciences and nanotechnology and shows advantages of their application.

  15. Hydrogel of Ketoconazole and PAMAM Dendrimers: Formulation and Antifungal Activity

    Directory of Open Access Journals (Sweden)

    Elzbieta Tryniszewska

    2012-04-01

    Full Text Available Ketoconazole (KET, an imidazole derivative with well-known antifungal properties, is lipophilic and practically insoluble in water, therefore its clinical use has some practical disadvantages. The aim of the present study was to investigate the influence of PAMAM-NH2 and PAMAM-OH dendrimers generation 2 and generation 3 on the solubility and antifungal activity of KET and to design and evaluate KET hydrogel with PAMAM dendrimers. It was shown that the surface charge of PAMAM dendrimers strongly affects their influence on the improvement of solubility and antifungal activity of KET. The MIC and MFC values obtained by broth dilution method indicate that PAMAM-NH2 dendrimers significantly (up to 16-fold increased the antifungal activity of KET against Candida strains (e.g., in culture Candida albicans 1103059/11 MIC value was 0.008 μg/mL and 0.064 μg/mL, and MFC was 2 μg/mL and 32 μg/mL for KET in 10 mg/mL solution of PAMAM-NH2 G2 and pure KET, respectively. Antifungal activity of designed KET hydrogel with PAMAM-NH2 dendrimers measured by the plate diffusion method was definitely higher than pure KET hydrogel and than commercial available product. It was shown that the improvement of solubility and in the consequence the higher KET release from hydrogels seems to be a very significant factor affecting antifungal activity of KET in hydrogels containing PAMAM dendrimers.

  16. Analysis of the spatial structure of rigid polyphenylene dendrimers by small-angle neutron scattering

    International Nuclear Information System (INIS)

    Rosenfeldt, S.; Dingenouts, N.; Poetschke, D.; Ballauff, M.; Berresheim, A.J.; Muellen, K.; Lindner, P.; Saalwaechter, K.

    2005-01-01

    The analysis of the spatial structure of a rigid polyphenylene dendrimer G4-M of fourth generation by small-angle neutron scattering (SANS) is presented. This dendrimer is composed of phenyl units and is therefore devoid of any flexible unit. The scattering intensity of dilute solutions of the dendrimer was measured by SANS at different contrast which was adjusted by mixtures of protonated and deuterated toluene. Hence, the method of contrast variation could be applied and the data yield the scattering function extrapolated to infinite contrast. The comparison of this data with simulations demonstrates that the scaffold of the dendrimer is rigid as expected from its chemical structure. The positions of the various units setting up consecutive shells of the dendrimer are relatively well localized and the entire structure cannot be modeled in terms of spherically symmetric models. No backfolding of the terminal groups can occur and the model calculations demonstrate that higher generations of this dendritic scaffold must exhibit a dense shell and a congestion of the terminal groups. This finding is directly corroborated by recent solid-state NMR data. All results show that the rigid dendrimer investigated here presents the first example for a dendritic structure whose segment density does not have its maximum at the center. Rigid scaffolds are therefore the only way to achieve the goal of a 'dense-shell' dendrimer whereas flexible scaffolds leads invariably to the 'dense-core' case

  17. Polyamidoamine (PAMAM) Dendrimer Conjugates of Clickable Agonists of the A3 Adenosine Receptor and Coactivation of the P2Y14 Receptor by a Tethered Nucleotide

    Energy Technology Data Exchange (ETDEWEB)

    Tosh, Dilip, K. [National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Yoo, Lena S. [National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Chinn, Moshe [National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Hong, Kunlun [ORNL; Kilbey, II, S Michael [ORNL; Barrett, Matthew O. [University of North Carolina School of Medicine; Fricks, Ingrid P. [University of North Carolina School of Medicine; Harden, T. Kendall [University of North Carolina School of Medicine; Jacobson, Kenneth A. [National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health

    2010-01-01

    We previously synthesized a series of potent and selective A{sub 3} adenosine receptor (AR) agonists (North-methanocarba nucleoside 5{prime}-uronamides) containing dialkyne groups on extended adenine C2 substituents. We coupled the distal alkyne of a 2-octadiynyl nucleoside by Cu(I)-catalyzed 'click' chemistry to azide-derivatized G4 (fourth-generation) PAMAM dendrimers to form triazoles. A{sub 3}AR activation was preserved in these multivalent conjugates, which bound with apparent Ki of 0.1-0.3 nM. They were substituted with nucleoside moieties, solely or in combination with water-solubilizing carboxylic acid groups derived from hexynoic acid. A comparison with various amide-linked dendrimers showed that triazole-linked conjugates displayed selectivity and enhanced A{sub 3}AR affinity. We prepared a PAMAM dendrimer containing equiproportioned peripheral azido and amino groups for conjugation of multiple ligands. A bifunctional conjugate activated both A{sub 3} and P2Y{sub 14} receptors (via amide-linked uridine-5{prime}-diphosphoglucuronic acid), with selectivity in comparison to other ARs and P2Y receptors. This is the first example of targeting two different GPCRs with the same dendrimer conjugate, which is intended for activation of heteromeric GPCR aggregates. Synergistic effects of activating multiple GPCRs with a single dendrimer conjugate might be useful in disease treatment.

  18. Assess the Intra-molecular Cavity in PAMAM Dendrimers by Small Angle Neutron Scattering

    International Nuclear Information System (INIS)

    Chen, Wei-Ren

    2008-01-01

    In this report, we present a contrast variation small angle neutron scattering (SANS) study of a series of neutral PAMAM dendrimer in aqueous solutions using three different generations (G4-6) at a concentration of about 10 mg/ml. Varying the solvent hydrogen-deuterium ratio, the scattering contributions from the water molecules and the constituent components of PAMAM dendrimer can be determined. Using an analytical model of the scattering cross section I(Q) incorporating the effect of water penetration, we have quantified the intra-molecular space of PAMAM dendrimer by evaluating the number of guest water molecules and we draw a direct comparison to computational predictions. As expected, the overall available internal cavity was seen to increase as a function of increasing dendrimer generation. However, the fraction of water accessible volume in the internal cavity of a dendrimer was found to remain invariant for the three generation PAMAM dendrimers studied in this report. We have also estimated the average water density inside a dendrimer, which is found to be higher than that of bulk water

  19. Dendrimers in drug delivery and targeting: Drug-dendrimer interactions and toxicity issues

    Directory of Open Access Journals (Sweden)

    Kanika Madaan

    2014-01-01

    Full Text Available Dendrimers are the emerging polymeric architectures that are known for their defined structures, versatility in drug delivery and high functionality whose properties resemble with biomolecules. These nanostructured macromolecules have shown their potential abilities in entrapping and/or conjugating the high molecular weight hydrophilic/hydrophobic entities by host-guest interactions and covalent bonding (prodrug approach respectively. Moreover, high ratio of surface groups to molecular volume has made them a promising synthetic vector for gene delivery. Owing to these properties dendrimers have fascinated the researchers in the development of new drug carriers and they have been implicated in many therapeutic and biomedical applications. Despite of their extensive applications, their use in biological systems is limited due to toxicity issues associated with them. Considering this, the present review has focused on the different strategies of their synthesis, drug delivery and targeting, gene delivery and other biomedical applications, interactions involved in formation of drug-dendrimer complex along with characterization techniques employed for their evaluation, toxicity problems and associated approaches to alleviate their inherent toxicity.

  20. Dendrimers in drug delivery and targeting: Drug-dendrimer interactions and toxicity issues

    Science.gov (United States)

    Madaan, Kanika; Kumar, Sandeep; Poonia, Neelam; Lather, Viney; Pandita, Deepti

    2014-01-01

    Dendrimers are the emerging polymeric architectures that are known for their defined structures, versatility in drug delivery and high functionality whose properties resemble with biomolecules. These nanostructured macromolecules have shown their potential abilities in entrapping and/or conjugating the high molecular weight hydrophilic/hydrophobic entities by host-guest interactions and covalent bonding (prodrug approach) respectively. Moreover, high ratio of surface groups to molecular volume has made them a promising synthetic vector for gene delivery. Owing to these properties dendrimers have fascinated the researchers in the development of new drug carriers and they have been implicated in many therapeutic and biomedical applications. Despite of their extensive applications, their use in biological systems is limited due to toxicity issues associated with them. Considering this, the present review has focused on the different strategies of their synthesis, drug delivery and targeting, gene delivery and other biomedical applications, interactions involved in formation of drug-dendrimer complex along with characterization techniques employed for their evaluation, toxicity problems and associated approaches to alleviate their inherent toxicity. PMID:25035633

  1. Dendrimer encapsulated Silver nanoparticles as novel catalysts for reduction of aromatic nitro compounds

    Science.gov (United States)

    Asharani, I. V.; Thirumalai, D.; Sivakumar, A.

    2017-11-01

    Polyethylene glycol (PEG) core dendrimer encapsulated silver nanoparticles (AgNPs) were synthesized through normal chemical reduction method, where dendrimer acts as reducing and stabilizing agent. The encapsulated AgNPs were well characterized using TEM, DLS and XPS techniques. The synthesized AgNPs showed excellent catalytic activity towards the reduction of aromatic nitro compounds with sodium borohydride as reducing agent and the results substantiate that dendrimer encapsulated AgNPs can be an effective catalyst for the substituted nitro aromatic reduction reactions. Also the kinetics of different nitro compounds reductions was studied and presented.

  2. Modified PAMAM dendrimer with 4-carbomethoxypyrrolidone surface groups reveals negligible toxicity against three rodent cell-lines

    DEFF Research Database (Denmark)

    Janaszewska, Anna; Ciolkowski, Michal; Wróbel, Dominika

    2013-01-01

    Modification of the surface groups of dendrimers is one of the methods to improve their biocompatibility. This article presents results of experiments related to the toxicity of a modified polyamidoamine (PAMAM) dendrimer of the fourth generation with 4-carbomethoxypyrrolidone surface groups (PAM...

  3. Exploring architectures displaying multimeric presentations of a trihydroxypiperidine iminosugar

    Directory of Open Access Journals (Sweden)

    Camilla Matassini

    2015-12-01

    Full Text Available The synthesis of new multivalent architectures based on a trihydroxypiperidine α-fucosidase inhibitor is reported herein. Tetravalent and nonavalent dendrimers were obtained by means of the click chemistry approach involving the copper azide-alkyne-catalyzed cycloaddition (CuAAC between suitable scaffolds bearing terminal alkyne moieties and an azido-functionalized piperidine as the bioactive moiety. A preliminary biological investigation is also reported towards commercially available and human glycosidases.

  4. Principal Physicochemical Methods Used to Characterize Dendrimer Molecule Complexes Used as Genetic Therapy Agents, Nanovaccines or Drug Carriers.

    Science.gov (United States)

    Alberto, Rodríguez Fonseca Rolando; Joao, Rodrigues; de Los Angeles, Muñoz-Fernández María; Alberto, Martínez Muñoz; Manuel Jonathan, Fragoso Vázquez; José, Correa Basurto

    2017-08-30

    Nanomedicine is the application of nanotechnology to medicine. This field is related to the study of nanodevices and nanomaterials applied to various medical uses, such as in improving the pharmacological properties of different molecules. Dendrimers are synthetic nanoparticles whose physicochemical properties vary according to their chemical structure. These molecules have been extensively investigated as drug nanocarriers to improve drug solubility and as sustained-release systems. New therapies such as gene therapy and the development of nanovaccines can be improved by the use of dendrimers. The biophysical and physicochemical characterization of nucleic acid/peptide-dendrimer complexes is crucial to identify their functional properties prior to biological evaluation. In that sense, it is necessary to first identify whether the peptide-dendrimer or nucleic aciddendrimer complexes can be formed and whether the complex can dissociate under the appropriate conditions at the target cells. In addition, biophysical and physicochemical characterization is required to determine how long the complexes remain stable, what proportion of peptide or nucleic acid is required to form the complex or saturate the dendrimer, and the size of the complex formed. In this review, we present the latest information on characterization systems for dendrimer-nucleic acid, dendrimer-peptide and dendrimer-drug complexes with several biotechnological and pharmacological applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Control of mobility in molecular organic semiconductors by dendrimer generation

    Science.gov (United States)

    Lupton, J. M.; Samuel, I. D.; Beavington, R.; Frampton, M. J.; Burn, P. L.; Bässler, H.

    2001-04-01

    Conjugated dendrimers are of interest as novel materials for light-emitting diodes. They consist of a luminescent chromophore at the core with highly branched conjugated dendron sidegroups. In these materials, light emission occurs from the core and is independent of generation. The dendron branching controls the separation between the chromophores. We present here a family of conjugated dendrimers and investigate the effect of dendron branching on light emission and charge transport. We apply a number of transport measurement techniques to thin films of a conjugated dendrimer in a light-emitting diode configuration to determine the effect of chromophore spacing on charge transport. We find that the mobility is reduced by two orders of magnitude as the size of the molecule doubles with increased branching or dendrimer generation. The degree of branching allows a unique control of mobility by molecular structure. An increase in chromophore separation also results in a reduction of intermolecular interactions, which reduces the red emission tail in film photoluminescence. We find that the steady-state charge transport is well described by a simple device model incorporating the effect of generation, and use the materials to shed light on the interpretation of transient electroluminescence data. We demonstrate the significance of the ability to tune the mobility in bilayer devices, where a more balanced charge transport can be achieved.

  6. Perspective: Dendrimer drugs for infection and inflammation.

    Science.gov (United States)

    Shaunak, Sunil

    2015-12-18

    Biologists are dissecting complex biological pathways at breath taking speed. It is opening up new opportunities for the therapeutic evaluation of novel dendrimer drugs. This review focuses on studies of small dendrimers decorated with sulfate, phosphonate, N-acetyl-cysteine, glucosamine and mannose in animal model studies of infection and inflammation. It highlights those animal model studies which have demonstrated the most promising dendrimer drug constructs as potential new medicines. The issues relating to their analytical chemistry that are slowing the progress of dendrimer drugs into the clinic are highlighted. It should be possible to solve these with additional analytical expertise because it is small dendrimers with only 16-32 peripheral groups that make for the best infection and inflammation related medicines. Public-private partnerships are now needed to progress these dendrimer drugs into proof-of-concept clinical trials. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Review Dendrimer : Definisi, Sintesis, Aplikasi Dan Prospektif

    OpenAIRE

    Rahmi, Dwinna

    2013-01-01

    Dendrimer merupakan makrostruktur monodisperse dengan banyak cabang yang homogen dan degree of branching (DB) 100%. Dua cara sintesis dendrimer yaitu convergent dan divergent dilakukan. Convergent dilakukan dengan reaksi kovalen antara dua dan lebih monomer. Divergent dimulai dengan pembentukan inti dilanjutkan dengan pembentukan cabang yang merupakan group fungsional yang aktif. Sejauh ini dendrimer sudah banyak diterapkan pada bidang farmasi yaitu drug delivery dan non farmasi pada proses i...

  8. Argument estimates of certain multivalent functions involving a linear operator

    Directory of Open Access Journals (Sweden)

    Nak Eun Cho

    2002-01-01

    Full Text Available The purpose of this paper is to derive some argument properties of certain multivalent functions in the open unit disk involving a linear operator. We also investigate their integral preserving property in a sector.

  9. Development of 2 multivalent RVF vaccines for improved uptake in ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2018-04-06

    Apr 6, 2018 ... Home · Resources · Publications. Development of 2 multivalent RVF vaccines for improved uptake in cattle and in small ruminants ... concern in recent years, with an increasing number of human cases recorded in Mauritania, ...

  10. Morphological and structural characterizations of dendrimer-mediated metallic Ti and Al thin film nanocomposites

    Energy Technology Data Exchange (ETDEWEB)

    Curry, M. [Center for Materials for Information Technology, University of Alabama, Tuscaloosa, AL 35487-0209 (United States); Department of Chemistry, University of Alabama, Tuscaloosa, AL 35487-0209 (United States); Li, X. [Center for Materials for Information Technology, University of Alabama, Tuscaloosa, AL 35487-0209 (United States); Department of Metallurgical and Materials Science and Engineering, University of Alabama, Tuscaloosa, AL 35487-0209 (United States); Zhang, J. [Center for Materials for Information Technology, University of Alabama, Tuscaloosa, AL 35487-0209 (United States); Department of Chemistry, University of Alabama, Tuscaloosa, AL 35487-0209 (United States); Weaver, M.L. [Center for Materials for Information Technology, University of Alabama, Tuscaloosa, AL 35487-0209 (United States); Department of Metallurgical and Materials Science and Engineering, University of Alabama, Tuscaloosa, AL 35487-0209 (United States); Street, S.C. [Center for Materials for Information Technology, University of Alabama, Tuscaloosa, AL 35487-0209 (United States) and Department of Chemistry, University of Alabama, Tuscaloosa, AL 35487-0209 (United States)]. E-mail: sstreet@bama.ua.edu

    2007-02-26

    Evidence is presented here for significant influence on the surface topography of Ti and Al films in the presence of poly(amidoamine) dendrimer monolayers [generations G(4-8)] on SiO {sub x}. X-ray photoelectron spectroscopy analysis clearly indicates formation of nitrides and carbides for Ti metal grown on dendrimer monolayers. In addition, obvious trends in measured correlation lengths and crystalline growth modes of Ti films indicate grain sizes tracking the intrinsic roughness of dendrimer monolayers. No formation of metal nitride is observed for Al depositions. Atomic force microscopy analyses show significant changes in rms vertical roughness and aggregation of as-deposited Ti or Al in presence of dendrimer monolayers.

  11. Aptamer-conjugated dendrimer-modified quantum dots for glioblastoma cells imaging

    International Nuclear Information System (INIS)

    Li Zhiming; Huang Peng; He Rong; Bao Chenchen; Cui Daxiang; Zhang Xiaomin; Ren Qiushi

    2009-01-01

    Targeted quantum dots have shown potential as a platform for development of cancer imaging. Aptamers have recently been demonstrated as ideal candidates for molecular targeting applications. In present work, polyamidoamine dendrimers were used to modify surface of quantum dots and improve their solubility in water solution. Then, dendrimer-modified quantum dots were conjugated with DNA aptamer, GBI-10, can recognize the extracellular matrix protein tenascin-C on the surface of human glioblastoma cells. The dendrimer-modified quantum dots exhibit water-soluble, high quantum yield, and good biocompatibility. Aptamer-conjugated quantum dots can specifically target U251 human glioblastoma cells. High-performance aptamer-conjugated dendrimers modified quantum dot-based nanoprobes have great potential in application such as cancer imaging.

  12. Polyelectrolyte Properties in Mono and Multi-Valent Ionic Media: Brushes and Complex Coacervates

    Science.gov (United States)

    Farina, Robert M.

    Materials composed of polyelectrolytes have unique and interesting physical properties resulting primarily from their charged monomer segments. Polyelectrolytes, which exist in many different biological and industrial forms, have also been shown to be highly responsive to external environmental changes. Here, two specific polyelectrolyte systems, brushes and complex coacervates, are discussed in regards to how their properties can be tailored by adjusting the surrounding ionic environment with mono and multi-valent ions. End-tethered polyelectrolyte brushes, which constitute an interesting and substantial portion of polyelectrolyte applications, are well known for their ability to provide excellent lubrication and low friction when coated onto surfaces (e.g. articular cartilage and medical devices), as well as for their ability to stabilize colloidal particles in solution (e.g. paint and cosmetic materials). These properties have been extensively studied with brushes in pure mono-valent ionic media. However, polyelectrolyte brush interactions with multi-valent ions in solution are much less understood, although highly relevant considering mono and multi-valent counterions are present in most applications. Even at very low concentrations of multi-valent ions in solution, dramatic polyelectrolyte brush physical property changes can occur, resulting in collapsed chains which also adhere to one another via multi-valent bridging. Here, the strong polyelectrolyte poly(sodium styrene sulfonate) was studied using the Surface Forces Apparatus (SFA) and electrochemistry in order to investigate brush height and intermolecular interactions between two brushes as a function of multi-valent counterion population inside a brush. Complex coacervates are formed when polyanions and polycations are mixed together in proper conditions of an aqueous solution. This mixing results in a phase separation of a polymer-rich, coacervate phase composed of a chain network held together via

  13. In Vitro Evaluation of Third Generation PAMAM Dendrimer Conjugates

    Directory of Open Access Journals (Sweden)

    Mohammad Najlah

    2017-10-01

    Full Text Available The present study compares the use of high generation G3 and low generation G0 Polyamidoamine (PAMAM dendrimers as drug carriers of naproxen (NAP, a poorly water soluble drug. Naproxen was conjugated to G3 in different ratios and to G0 in a 1:1 ratio via a diethylene glycol linker. A lauroyl chain (L, a lipophilic permeability enhancer, was attached to G3 and G0 prodrugs. The G3 and G0 conjugates were more hydrophilic than naproxen as evaluated by the measurement of partitioning between 1-octanol and a phosphate buffer at pH 7.4 and pH 1.2. The unmodified surface PAMAM-NAP conjugates showed significant solubility enhancements of NAP at pH 1.2; however, with the number of NAP conjugated to G3, this was limited to 10 molecules. The lactate dehydrogenase (LDH assay indicated that the G3 dendrimer conjugates had a concentration dependent toxicity towards Caco-2 cells. Attaching naproxen to the surface of the dendrimer increased the IC50 of the resulting prodrugs towards Caco-2 cells. The lauroyl G3 conjugates showed the highest toxicity amongst the PAMAM dendrimer conjugates investigated and were significantly more toxic than the lauroyl-G0-naproxen conjugates. The permeability of naproxen across monolayers of Caco-2 cells was significantly increased by its conjugation to either G3 or G0 PAMAM dendrimers. Lauroyl-G0 conjugates displayed considerably lower cytotoxicity than G3 conjugates and may be preferable for use as a drug carrier for low soluble drugs such as naproxen.

  14. Designing Dendrimer and Miktoarm Polymer Based Multi-Tasking Nanocarriers for Efficient Medical Therapy.

    Science.gov (United States)

    Sharma, Anjali; Kakkar, Ashok

    2015-09-17

    To address current complex health problems, there has been an increasing demand for smart nanocarriers that could perform multiple complimentary biological tasks with high efficacy. This has provoked the design of tailor made nanocarriers, and the scientific community has made tremendous effort in meeting daunting challenges associated with synthetically articulating multiple functions into a single scaffold. Branched and hyper-branched macromolecular architectures have offered opportunities in enabling carriers with capabilities including location, delivery, imaging etc. Development of simple and versatile synthetic methodologies for these nanomaterials has been the key in diversifying macromolecule based medical therapy and treatment. This review highlights the advancement from conventional "only one function" to multifunctional nanomedicine. It is achieved by synthetic elaboration of multivalent platforms in miktoarm polymers and dendrimers by physical encapsulation, covalent linking and combinations thereof.

  15. Designing Dendrimer and Miktoarm Polymer Based Multi-Tasking Nanocarriers for Efficient Medical Therapy

    Directory of Open Access Journals (Sweden)

    Anjali Sharma

    2015-09-01

    Full Text Available To address current complex health problems, there has been an increasing demand for smart nanocarriers that could perform multiple complimentary biological tasks with high efficacy. This has provoked the design of tailor made nanocarriers, and the scientific community has made tremendous effort in meeting daunting challenges associated with synthetically articulating multiple functions into a single scaffold. Branched and hyper-branched macromolecular architectures have offered opportunities in enabling carriers with capabilities including location, delivery, imaging etc. Development of simple and versatile synthetic methodologies for these nanomaterials has been the key in diversifying macromolecule based medical therapy and treatment. This review highlights the advancement from conventional “only one function” to multifunctional nanomedicine. It is achieved by synthetic elaboration of multivalent platforms in miktoarm polymers and dendrimers by physical encapsulation, covalent linking and combinations thereof.

  16. A combinatorial approach of inclusion complexation and dendrimer synthesization for effective targeting EGFR-TK.

    Science.gov (United States)

    Shende, Pravin; Patil, Sampada; Gaud, R S

    2017-07-01

    The aim of the present study was to use a combinatorial approach of inclusion complexation and dendrimer synthesization of gefitinib using solvent-free technique for targeting EGFR-TK to treat Non-Small-Cell Lung Cancer (NSCLC). The inclusion complex of gefitinib with β-cyclodextrin was prepared by trituration method. This complex encapsulated G4 PAMAM dendrimers were synthesized by Michael addition and amidation reactions using green chemistry and then PEGylated by conjugation reaction. FTIR and DSC confirmed the formation of inclusion complex of gefitinib and β-cyclodextrin and PEGylation of G4 PAMAM dendrimers. Gefitinib showed higher solubility, encapsulation efficiency and controlled release profile from PEGylated dendrimers compared to inclusion complex. The PEGylated dendrimers of inclusion complex of gefitinib were found to reduce hemolytic toxicity and lesser GI 50 value on Human lung cancer cell line A-549 by effective targeting EGFR-TK. A combinatorial approach of inclusion complexation and dendrimer synthesization is one of the alternative advanced approaches to treat NSCLC. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Dendrimer-based dynamic combinatorial libraries

    NARCIS (Netherlands)

    Chang, T.; Meijer, E.W.

    2005-01-01

    The aim of this project is to create water-sol. dynamic combinatorial libraries based upon dendrimer-guest complexes. The guest mols. are designed to bind to dendrimers using multiple secondary interactions, such as electrostatics and hydrogen bonding. We have been able to incorporate various guest

  18. Influence of microorganisms on the oxidation state distribution of multivalent actinides under anoxic conditions

    International Nuclear Information System (INIS)

    Reed, Donald Timothy; Borkowski, Marian; Lucchini, Jean-Francois; Ams, David; Richmann, M.K.; Khaing, H.; Swanson, J.S.

    2010-01-01

    The fate and potential mobility of multivalent actinides in the subsurface is receiving increased attention as the DOE looks to cleanup the many legacy nuclear waste sites and associated subsurface contamination. Plutonium, uranium and neptunium are the near-surface multivalent contaminants of concern and are also key contaminants for the deep geologic disposal of nuclear waste. Their mobility is highly dependent on their redox distribution at their contamination source as well as along their potential migration pathways. This redox distribution is often controlled, especially in the near-surface where organic/inorganic contaminants often coexist, by the direct and indirect effects of microbial activity. Under anoxic conditions, indirect and direct bioreduction mechanisms exist that promote the prevalence of lower-valent species for multivalent actinides. Oxidation-state-specific biosorption is also an important consideration for long-term migration and can influence oxidation state distribution. Results of ongoing studies to explore and establish the oxidation-state specific interactions of soil bacteria (metal reducers and sulfate reducers) as well as halo-tolerant bacteria and Archaea for uranium, neptunium and plutonium will be presented. Enzymatic reduction is a key process in the bioreduction of plutonium and uranium, but co-enzymatic processes predominate in neptunium systems. Strong sorptive interactions can occur for most actinide oxidation states but are likely a factor in the stabilization of lower-valent species when more than one oxidation state can persist under anaerobic microbiologically-active conditions. These results for microbiologically active systems are interpreted in the context of their overall importance in defining the potential migration of multivalent actinides in the subsurface.

  19. Research progress on synthesis and characteristic about dendrimers

    Science.gov (United States)

    Tang, Zitao

    2017-12-01

    Dendrimers are hyper-branched polymers which have perfectly defined structures. Different from the common polymers, dendrimers are synthesized by a step-by-step iterative style, which starts from a central core and forms branching parts outward. The dendrimers also have different physical and chemical characteristics from common polymers. In this paper, contributions to dendrimer synthesis from different researchers with different scientific background, synthesis of different dendrimers, and applications of them will be reviewed.

  20. Novel Approach to Prepare {sup 99m}Tc-Based Multivalent RGD Peptides

    Energy Technology Data Exchange (ETDEWEB)

    Shuang Liu

    2012-10-24

    This project presents a novel approach to prepare the {sup 99m}Tc-bridged multivalent RGD (arginine-glycine-aspartate) peptides. This project will focus on fundamentals of {sup 99m}Tc radiochemistry. The main objective of this project is to demonstrate the proof-of-principle for the proposed radiotracers. Once a kit formulation is developed for preparation of the {sup 99m}Tc-bridged multivalent RGD peptides, various tumor-bearing animal models will be used to evaluate their potential for SPECT (single photon-emission computed tomography) imaging of cancer. We have demonstrated that (1) multimerization of cyclic RGD peptides enhances the integrin {alpha}{sub v}{beta}{sub 3} bonding affinity and radiotracer tumor uptake; (2) addition of G{sub 3} or PEG{sub 4} linkers makes it possible for two RGD motifs in 3P-RGD{sub 2} and 3G-RGD{sub 2} to achieve simultaneous integrin {alpha}{sub v}{beta}{sub 3} binding; and (3) multimers are actually bivalent (not multivalent), the presence of extra RGD motifs can enhance the tumor retention time of the radiotracer.

  1. Dendrimers for siRNA Delivery

    Directory of Open Access Journals (Sweden)

    Swati Biswas

    2013-02-01

    Full Text Available Since the discovery of the “starburst polymer”, later renamed as dendrimer, this class of polymers has gained considerable attention for numerous biomedical applications, due mainly to the unique characteristics of this macromolecule, including its monodispersity, uniformity, and the presence of numerous functionalizable terminal groups. In recent years, dendrimers have been studied extensively for their potential application as carriers for nucleic acid therapeutics, which utilize the cationic charge of the dendrimers for effective dendrimer-nucleic acid condensation. siRNA is considered a promising, versatile tool among various RNAi-based therapeutics, which can effectively regulate gene expression if delivered successfully inside the cells. This review reports on the advancements in the development of dendrimers as siRNA carriers.

  2. Influence of dendrimer generation and polyethylene glycol length on the biodistribution of PEGylated dendrimers.

    Science.gov (United States)

    Kojima, Chie; Regino, Celeste; Umeda, Yasuhito; Kobayashi, Hisataka; Kono, Kenji

    2010-01-04

    Dendrimers are a potential drug carrier. Because modification with polyethylene glycol (PEG) is known to improve the blood retention, PEGylated dendrimers have been studied as a useful drug carrier. In this study, three types of PEGylated L-lysine-bearing polyamidoamine dendrimers (PEG2k-Lys-PAMAM (G4), PEG5k-Lys-PAMAM (G4), PEG2k-Lys-PAMAM (G5)) were synthesized, which are composed of a dendrimer of different generations (generations 4 and 5) and PEG chains with different molecular weights (2k and 5k). An acetylated L-lysine-bearing dendrimer was also synthesized as a non-PEGylated dendrimer. Bifunctional diethylenetriaminepentaacetic acid (pSCN-benzyl-DTPA) was bound to the epsilon -amino group of lysine in a dendrimer, to be labeled with radioactive indium-111. These PEGylayed dendrimers showed longer blood retention and lower accumulation in other normal organs such as the kidneys than the non-PEGylated dendrimer. The PEGylated dendrimers with the higher generation and the longer PEG led the greater blood retention.

  3. Stability of anionic polymers in presence of multivalent cations

    International Nuclear Information System (INIS)

    Sabbagh, Imad

    1997-01-01

    This research thesis aimed at studying the stability of poly-electrolytes in saline environments, and the interactions between ions and poly-electrolytes of different charge densities. For this purpose, the author more particularly studied specific interactions between anionic poly-electrolytes and multivalent cations. After a recall of properties of neutral polymers and poly-electrolytes in solution, the author evokes interactions between poly-electrolytes and counter-ions, and briefly presents two models of stability of poly-electrolytes in saline solutions. The next part presents various experimental spectroscopic and electrochemical techniques and results of the characterization of the used products. Spectroscopic techniques allow ion-polymer interactions at the atomic scale to be studied, and electrochemical techniques allow the behaviour of small ions to be studied. The author then discusses the main differences of solubility between poly-electrolytes containing sulphonate or sulphate groups and those containing carboxylate groups. A model is then developed to generalise phase diagrams of a poly-electrolyte with respect to the chemical affinity of its functional group with ions of opposite sign. The author then addresses the behaviour of a non charged polyacrylic acid in various saline solutions, and presents a phase diagram model [fr

  4. Aqueous synthesis of ZnTe/dendrimer nanocomposites and their antimicrobial activity: implications in therapeutics

    Science.gov (United States)

    Ghosh, S.; Ghosh, D.; Bag, P. K.; Bhattacharya, S. C.; Saha, A.

    2011-03-01

    The present strategy proposes a simple and single step aqueous route for synthesizing stable, fluorescent ZnTe/dendrimer nanocomposites with varying dendrimer terminal groups. In these hybrid materials, the fluorescence of the semiconductor combines with the biomimetic properties of the dendrimer making them suitable for various biomedical applications. The ZnTe nanocomposites thus obtained demonstrate bactericidal activity against enteropathogenic bacteria without having toxic effects on the human erythrocytes. The average size of the ZnTe nanoparticles within the dendrimer matrix was in the range of 2.9-6.0 nm, and they have a good degree of crystallinity with a hexagonal crystal phase. The antibacterial activities of the ZnTe/dendrimer nanocomposites (ZnTe DNCs) as well other semiconductor nanocomposites were evaluated against enteropathogenic bacteria including multi-drug resistant Vibrio cholerae serogroup O1 and enterotoxigenic Escherichia coli (ETEC). ZnTe DNCs had significant antibacterial activity against strains of V. cholerae and ETEC with minimum inhibitory concentrations ranging from 64 to 512 μg ml-1 and minimum bactericidal concentrations ranging from 128 to 1000 μg ml-1. Thus, the observed results suggest that these water-soluble active nanocomposites have potential for the treatment of enteric diseases like diarrhoea and cholera.The present strategy proposes a simple and single step aqueous route for synthesizing stable, fluorescent ZnTe/dendrimer nanocomposites with varying dendrimer terminal groups. In these hybrid materials, the fluorescence of the semiconductor combines with the biomimetic properties of the dendrimer making them suitable for various biomedical applications. The ZnTe nanocomposites thus obtained demonstrate bactericidal activity against enteropathogenic bacteria without having toxic effects on the human erythrocytes. The average size of the ZnTe nanoparticles within the dendrimer matrix was in the range of 2.9-6.0 nm, and they

  5. Spatial distribution of intra-molecular water and polymeric components in polyelectrolyte dendrimers revealed by small angle scattering investigations

    Science.gov (United States)

    Wu, Bin; Li, Xin; Do, Changwoo; Kim, Tae-Hwan; Shew, Chwen-Yang; Liu, Yun; Yang, Jun; Hong, Kunlun; Porcar, Lionel; Chen, Chun-Yu; Liu, Emily L.; Smith, Gregory S.; Herwig, Kenneth W.; Chen, Wei-Ren

    2011-10-01

    An experimental scheme using contrast variation small angle neutron scattering technique is developed to investigate the structural characteristics of amine-terminated poly(amidoamine) dendrimers solutions. Using this methodology, we present the dependence of both the intra-dendrimer water and the polymer distribution on molecular protonation, which can be precisely adjusted by tuning the pH of the solution. Assuming spherical symmetry of the spatial arrangement of the constituent components of dendrimer, and that the atomic ratio of hydrogen-to-deuterium for the solvent residing within the cavities of dendrimer is identical to that for the solvent outside the dendrimer, the intra-dendrimer water distribution along the radial direction is determined. Our result clearly reveals an outward relocation of the peripheral groups, as well as enhanced intra-dendrimer hydration, upon increasing the molecular protonation and, therefore, allows the determination of segmental backfolding in a quantitative manner. The connection between these charge-induced structural changes and our recently observed progressively active segmental dynamics is also discussed.

  6. On-Demand Bioadhesive Dendrimers with Reduced Cytotoxicity

    Directory of Open Access Journals (Sweden)

    Feng Gao

    2018-03-01

    Full Text Available Tissue adhesives based on polyamidoamine (PAMAM dendrimer, grafted with UV-sensitive aryldiazirine (PAMAM-g-diazirine are promising new candidates for light active adhesion on soft tissues. Diazirine carbene precursors form interfacial and intermolecular covalent crosslinks with tissues after UV light activation that requires no premixing or inclusion of free radical initiators. However, primary amines on the PAMAM dendrimer surface present a potential risk due to their cytotoxic and immunological effects. PAMAM-g-diazirine formulations with cationic pendant amines converted into neutral amide groups were evaluated. In vitro toxicity is reduced by an order of magnitude upon amine capping while retaining bioadhesive properties. The in vivo immunological response to PAMAM-g-diazirine formulations was found to be optimal in comparison to standard poly(lactic-co-glycolic acid (PLGA thin films.

  7. Poly(amidoamine) dendrimers on lipid bilayers II: Effects of bilayer phase and dendrimer termination.

    Science.gov (United States)

    Kelly, Christopher V; Leroueil, Pascale R; Orr, Bradford G; Banaszak Holl, Mark M; Andricioaei, Ioan

    2008-08-07

    The molecular structures and enthalpy release of poly(amidoamine) (PAMAM) dendrimers binding to 1,2-dimyristoyl- sn-glycero-3-phosphocholine (DMPC) bilayers were explored through atomistic molecular dynamics. Three PAMAM dendrimer terminations were examined: protonated primary amine, neutral acetamide, and deprotonated carboxylic acid. Fluid and gel lipid phases were examined to extract the effects of lipid tail mobility on the binding of generation-3 dendrimers, which are directly relevant to the nanoparticle interactions involving lipid rafts, endocytosis, lipid removal, and/or membrane pores. Upon binding to gel phase lipids, dendrimers remained spherical, had a constant radius of gyration, and approximately one-quarter of the terminal groups were in close proximity to the lipids. In contrast, upon binding to fluid phase bilayers, dendrimers flattened out with a large increase in their asphericity and radii of gyration. Although over twice as many dendrimer-lipid contacts were formed on fluid versus gel phase lipids, the dendrimer-lipid interaction energy was only 20% stronger. The greatest enthalpy release upon binding was between the charged dendrimers and the lipid bilayer. However, the stronger binding to fluid versus gel phase lipids was driven by the hydrophobic interactions between the inner dendrimer and lipid tails.

  8. Investigation of Dendrimer-Membrane Interactions

    Science.gov (United States)

    Mecke, Almut; Hessler, Jessica; Lee, Inhan; Banaszak Holl, Mark; Orr, Bradford; Patri, Anil K.; Baker, J. R.

    2003-03-01

    Modified Polyamidoamine (PAMAM) dendrimers show great promise as targeted drug transport agents. Current research efforts point to the possibility of dramatic improvements to conventional chemotherapy by selectively delivering a therapeutic to antigen bearing tumor cells. In order to better understand the uptake mechanism of such devices into cells we are investigating dendrimer-surface adsorption and dendrimer-membrane interactions using atomic force microscopy, light scattering and computer simulations. Model systems consisting of supported DMPC lipid bilayers have shown interesting results suggesting the shape and architecture of nano-devices play an important role for their biologic activity. We are also investigating the effect of targeted drug vehicles on cells in vitro.

  9. Light-emitting dendrimer film morphology: A neutron reflectivity study

    Science.gov (United States)

    Vickers, S. V.; Barcena, H.; Knights, K. A.; Thomas, R. K.; Ribierre, J.-C.; Gambino, S.; Samuel, I. D. W.; Burn, P. L.; Fragneto, Giovanna

    2010-06-01

    We have used neutron reflectivity (NR) measurements to probe the physical structure of phosphorescent dendrimer films. The dendrimers consisted of fac-tris(2-phenylpyridyl)iridium(III) cores, biphenyl-based dendrons (first or second generation), and perdeuterated 2-ethylhexyloxy surface groups. We found that the shape and hydrodynamic radius of the dendrimer were both important factors in determining the packing density of the dendrimers. "Cone" shaped dendrimers were found to pack more effectively than "spherical" dendrimers even when the latter had a smaller radius. The morphology of the films determined by NR was consistent with the measured photoluminescence and charge transporting properties of the materials.

  10. Second-Order Nonlinear Optical Dendrimers and Dendronized Hyperbranched Polymers.

    Science.gov (United States)

    Tang, Runli; Li, Zhen

    2017-01-01

    Second-order nonlinear optical (NLO) dendrimers with a special topological structure were regarded as the most promising candidates for practical applications in the field of optoelectronic materials. Dendronized hyperbranched polymers (DHPs), a new type of polymers with dendritic structures, proposed and named by us recently, demonstrated interesting properties and some advantages over other polymers. Some of our work concerning these two types of polymers are presented herein, especially focusing on the design idea and structure-property relationship. To enhance their comprehensive NLO performance, dendrimers were designed and synthesized by adjusting their isolation mode, increasing the number of the dendritic generation, modifying their topological structure, introducing isolation chromophores, and utilizing the Ar-Ar F self-assembly effect. To make full use of the advantages of both the structural integrity of dendrimers and the convenient one-pot synthesis of hyperbranched polymers, DHPs were explored by utilizing low-generation dendrons as big monomers to construct hyperbranched polymers. These selected works could provide valuable information to deeply understand the relationship between the structure and properties of functional polymers with dendritic structures, but not only limited to the NLO ones, and might contribute much to the further development of functional polymers with rational design. © 2017 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Formation of Silver and Gold Dendrimer Nanocomposites

    International Nuclear Information System (INIS)

    Balogh, Lajos; Valluzzi, Regina; Laverdure, Kenneth S.; Gido, Samuel P.; Hagnauer, Gary L.; Tomalia, Donald A.

    1999-01-01

    Structural types of dendrimer nanocomposites have been studied and the respective formation mechanisms have been described, with illustration of nanocomposites formed from poly(amidoamine) PAMAM dendrimers and zerovalent metals, such as gold and silver. Structure of {(Au(0)) n- PAMAM} and {(Ag(0)) n- PAMAM} gold and silver dendrimer nanocomposites was found to be the function of the dendrimer structure and surface groups as well as the formation mechanism and the chemistry involved. Three different types of single nanocomposite architectures have been identified, such as internal ('I'), external ('E') and mixed ('M') type nanocomposites. Both the organic and inorganic phase could form nanosized pseudo-continuous phases while the other components are dispersed at the molecular or atomic level either in the interior or on the surface of the template/container. Single units of these nanocomposites may be used as building blocks in the synthesis of nanostructured materials

  12. On Topological Indices of Certain Dendrimer Structures

    Science.gov (United States)

    Aslam, Adnan; Bashir, Yasir; Ahmad, Safyan; Gao, Wei

    2017-05-01

    A topological index can be considered as transformation of chemical structure in to real number. In QSAR/QSPR study, physicochemical properties and topological indices such as Randić, Zagreb, atom-bond connectivity ABC, and geometric-arithmetic GA index are used to predict the bioactivity of chemical compounds. Dendrimers are highly branched, star-shaped macromolecules with nanometer-scale dimensions. Dendrimers are defined by three components: a central core, an interior dendritic structure (the branches), and an exterior surface with functional surface groups. In this paper we determine generalised Randić, general Zagreb, general sum-connectivity indices of poly(propyl) ether imine, porphyrin, and zinc-Porphyrin dendrimers. We also compute ABC and GA indices of these families of dendrimers.

  13. Electronic transport study in PAMAM dendrimers

    International Nuclear Information System (INIS)

    Vieira, Nirton C.S.; Soares, Demetrio A.W.; Fernandes, Edson G.R.; Queiroz, Alvaro A.A. de

    2005-01-01

    Dendrimers are nanomaterials that have many potential applications in medicine, including diagnosis and therapeutic procedures. Dendrimers are isomolecular polymers, with a very well controlled architecture and a thousand times smaller than cells. Dendrimers containing biocatalysts are of great interest for clinical applications in biosensors because of the way in which their chemical and electric conduction mechanism can be tailored. In this work, the polyamidoamine dendrimer (PAMAM) of generation 4 was synthesized by divergent route and characterized by NMR spectroscopy. The electronic transport properties of PAMAM in a metal-polymer type heterojunction were studied. The electrical conduction mechanism of PAMAM studied in the temperature range of 291-323 K indicates a conduction mechanism thermally activated. (author)

  14. Enhanced Intestinal Permeability of Bufalin by a Novel Bufalin-Peptide-Dendrimer Inclusion through Caco-2 Cell Monolayer

    OpenAIRE

    Chi-on Chan; Jing Jing; Wei Xiao; Zhexu Tan; Qiuyue Lv; Jingyu Yang; Sibao Chen

    2017-01-01

    Bufalin (BFL) has excellent physiological activities such as defending tumors, improving cardiac function, and so on. However, due to its poor water-solubility and bioavailability, the clinical application of BFL remains limited. In order to improve bioavailability of BFL, in our previous research, a novel peptide-dendrimer (PD) was synthesized and applied to encapsulate BFL. In the present study, we investigate the absorption property and mechanism of BFL in free form and BFL-peptide-dendrim...

  15. Anomalous Protein-Protein Interactions in Multivalent Salt Solution

    Czech Academy of Sciences Publication Activity Database

    Pasquier, C.; Vazdar, M.; Forsman, J.; Jungwirth, Pavel; Lund, M.

    2017-01-01

    Roč. 121, č. 14 (2017), s. 3000-3006 ISSN 1520-6106 R&D Projects: GA ČR(CZ) GA16-01074S Institutional support: RVO:61388963 Keywords : Monte Carlo * molecular dynamics * membranes * proteins * multivalent salts Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Physical chemistry Impact factor: 3.177, year: 2016

  16. Multivalent protein assembly using monovalent self-assembling building blocks

    NARCIS (Netherlands)

    Petkau - Milroy, K.; Sonntag, M.H.; Colditz, A.; Brunsveld, L.

    2013-01-01

    Discotic molecules, which self-assemble in water into columnar supramolecular polymers, emerged as an alternative platform for the organization of proteins. Here, a monovalent discotic decorated with one single biotin was synthesized to study the self-assembling multivalency of this system in regard

  17. Study of Dendrimers by Topological Indices

    Directory of Open Access Journals (Sweden)

    Soleimani Najmeh

    2017-12-01

    Full Text Available In this paper, five degree based topological indices, the first Zagreb (M1, second Zagreb (M2, first multiple Zagreb (PM1, second multiple Zagreb (PM2, and the hyper Zagreb (HM indices of two types of dendrimers are studied. In addition, two distance based topological indices, the total eccentricity (θ and eccentric connectivity (ξc indices of these dendrimers are computed.

  18. Evaluation of Nanocarrier Targeted Drug Delivery of Capecitabine-PAMAM Dendrimer Complex in a Mice Colorectal Cancer Model

    Directory of Open Access Journals (Sweden)

    Fatemeh Nabavizadeh

    2016-09-01

    Full Text Available Capecitabine, an effective anticancer drug in colorectal cancer chemotherapy, may create adverse side effects on healthy tissues. In the present study, we first induced colon adenocarcinoma with azoxymethane, a carcinogen agent, and then investigated the potentiality of polyamidoamine (PAMAM dendrimer to improve capecitabine therapeutic index and decrease its adverse side effects on healthy tissues like liver and bone marrow. Other variables such as nanoparticle concentrations have also been investigated. Drug loading concentration (DLC and encapsulation efficiency (EE were calculated for capecitabine/dendrimer complex. Experimental results showed an increase in DLC percentage resulted from elevated capecitabine/dendrimer ratio. Capecitabine/dendrimer complex could reduce tumor size and adverse side effects in comparison with free capecitabine form.

  19. DNA condensation by partially acetylated poly(amido amine) dendrimers: effects of dendrimer charge density on complex formation.

    Science.gov (United States)

    Yu, Shi; Li, Ming-Hsin; Choi, Seok Ki; Baker, James R; Larson, Ronald G

    2013-09-03

    The ability of poly(amido amine) (or PAMAM) dendrimers to condense semiflexible dsDNA and penetrate cell membranes gives them great potential in gene therapy and drug delivery but their high positive surface charge makes them cytotoxic. Here, we describe the effects of partial neutralization by acetylation on DNA condensation using light scattering, circular dichroism, and single molecule imaging of dendrimer-DNA complexes combed onto surfaces and tethered to those surfaces under flow. We find that DNA can be condensed by generation-five (G5) dendrimers even when the surface charges are more than 65% neutralized, but that such dendrimers bind negligibly when an end-tethered DNA is stretched in flow. We also find that when fully charged dendrimers are introduced by flow to end-tethered DNA, all DNA molecules become equally highly coated with dendrimers at a rate that becomes very fast at high dendrimer concentration, and that dendrimers remain bound during subsequent flow of dendrimer-free buffer. These results suggest that the presence of dendrimer-free DNA coexisting with dendrimer-bound DNA after bulk mixing of the two in solution may result from diffusion-limited irreversible dendrimer-DNA binding, rather than, or in addition to, the previously proposed cooperative binding mechanism of dendrimers to DNA.

  20. DNA Condensation by Partially Acetylated Poly(amido amine Dendrimers: Effects of Dendrimer Charge Density on Complex Formation

    Directory of Open Access Journals (Sweden)

    Ronald G. Larson

    2013-09-01

    Full Text Available The ability of poly(amido amine (or PAMAM dendrimers to condense semiflexible dsDNA and penetrate cell membranes gives them great potential in gene therapy and drug delivery but their high positive surface charge makes them cytotoxic. Here, we describe the effects of partial neutralization by acetylation on DNA condensation using light scattering, circular dichroism, and single molecule imaging of dendrimer-DNA complexes combed onto surfaces and tethered to those surfaces under flow. We find that DNA can be condensed by generation-five (G5 dendrimers even when the surface charges are more than 65% neutralized, but that such dendrimers bind negligibly when an end-tethered DNA is stretched in flow. We also find that when fully charged dendrimers are introduced by flow to end-tethered DNA, all DNA molecules become equally highly coated with dendrimers at a rate that becomes very fast at high dendrimer concentration, and that dendrimers remain bound during subsequent flow of dendrimer-free buffer. These results suggest that the presence of dendrimer-free DNA coexisting with dendrimer-bound DNA after bulk mixing of the two in solution may result from diffusion-limited irreversible dendrimer-DNA binding, rather than, or in addition to, the previously proposed cooperative binding mechanism of dendrimers to DNA.

  1. New dendrimer - peptide host - guest complexes : towards dendrimers as peptide carriers

    NARCIS (Netherlands)

    Boas, U.; Sontjens, S.H.M.; Jensen, K.J.; Christensen, J.B.; Meijer, E.W.

    2002-01-01

    Adamantyl urea and adamantyl thiourea modified poly(propylene imine) dendrimers act as hosts for N-terminal tert-butoxycarbonyl (Boc)-protected peptides and form chloroform-soluble complexes. investigations with NMR spectroscopy show that the peptide is bound to the dendrimer by ionic interactions

  2. Brief Timelapse on Dendrimer Chemistry: Advances, Limitations, and Expectations

    KAUST Repository

    Ornelas, Catia

    2015-01-01

    , with a critical analysis on the expectations, limitations, advances, current challenges and future directions. Dendrimer timelapse demonstrates constant evolution in dendrimer chemistry enabling their application in nanomedicine, protein mimic, catalysis

  3. New dendrimer - Peptide host - Guest complexes: Towards dendrimers as peptide carriers

    DEFF Research Database (Denmark)

    Boas, Ulrik; Sontjens, S.H.M.; Jensen, Knud Jørgen

    2002-01-01

    Adamantyl urea and adamantyl thiourea modified poly(propylene imine) dendrimers act as hosts for N-terminal tert-butoxycarbonyl (Boc)-protected peptides and form chloroform-soluble complexes. investigations with NMR spectroscopy show that the peptide is bound to the dendrimer by ionic interactions...... between the dendrimer outer shell tertiary amines and the C-terminal carboxylic acid of the peptide, and also through host-urea to peptide-amide hydrogen bonding. The hydrogen-bonding nature of the peptide dendrimer interactions was further confirmed by using Fourier transform IR spectroscopy, for which...... the NH- and CO-stretch signals of the peptide amide moieties shift towards lower wave-numbers upon complexation with the dendrimer. Spatial analysis of the complexes with NOESY spectroscopy generally shows close proximity of the N-terminal Boc group of the peptide to the peripheral adamantyl groups...

  4. Polypropyleneimine and polyamidoamine dendrimer mediated enhanced solubilization of bortezomib: Comparison and evaluation of mechanistic aspects by thermodynamics and molecular simulations

    Energy Technology Data Exchange (ETDEWEB)

    Chaudhary, Sonam; Gothwal, Avinash; Khan, Iliyas; Srivastava, Shubham; Malik, Ruchi; Gupta, Umesh, E-mail: umeshgupta175@gmail.com

    2017-03-01

    Bortezomib (BTZ) is the first proteasome inhibitor approved by the US-FDA is majorly used for the treatment of newly diagnosed and relapsed multiple myeloma including mantle cell lymphoma. BTZ is hydrophobic in nature and is a major cause for its minimal presence as marketed formulations. The present study reports the design, development and characterization of dendrimer based formulation for the improved solubility and effectivity of bortezomib. The study also equally focuses on the mechanistic elucidation of solubilization by two types of dendrimers i.e. fourth generation of poly (amidoamine) dendrimers (G4-PAMAM-NH{sub 2}) and fifth generation of poly (propylene) imine dendrimers (G5-PPI-NH{sub 2}). It was observed that aqueous solubility of BTZ was concentration and pH dependent. At 2 mM G5-PPI-NH{sub 2} concentration, the fold increase in bortezomib solubility was 1152.63 times in water, while approximately 3426.69 folds increase in solubility was observed at pH 10.0, respectively (p < 0.05). The solubility of the drug was increased to a greater extent with G5-PPI-NH{sub 2} dendrimers because it has more hydrophobic interior than G4-PAMAM-NH{sub 2} dendrimers. The release of BTZ from G5-PPI-NH{sub 2} complex was comparatively slower than G4-PAMAM-NH{sub 2}. The thermodynamic treatment of data proved that dendrimer drug complexes were stable at all pH with values of ΔG always negative. The experimental findings were also proven by molecular simulation studies and by calculating RMSD and intermolecular hydrogen bonding through Schrodinger software. It was concluded that PPI dendrimers were able to solubilize the drug more effectively than PAMAM dendrimers through electrostatic interactions. - Highlights: • The present study reports the application of PAMAM and PPI dendrimers in solubilizing bortezomib with possible mechanism. • Improved solubility of bortezomib through dendrimers could significantly contribute its successful anticancer potential.

  5. Polypropyleneimine and polyamidoamine dendrimer mediated enhanced solubilization of bortezomib: Comparison and evaluation of mechanistic aspects by thermodynamics and molecular simulations

    International Nuclear Information System (INIS)

    Chaudhary, Sonam; Gothwal, Avinash; Khan, Iliyas; Srivastava, Shubham; Malik, Ruchi; Gupta, Umesh

    2017-01-01

    Bortezomib (BTZ) is the first proteasome inhibitor approved by the US-FDA is majorly used for the treatment of newly diagnosed and relapsed multiple myeloma including mantle cell lymphoma. BTZ is hydrophobic in nature and is a major cause for its minimal presence as marketed formulations. The present study reports the design, development and characterization of dendrimer based formulation for the improved solubility and effectivity of bortezomib. The study also equally focuses on the mechanistic elucidation of solubilization by two types of dendrimers i.e. fourth generation of poly (amidoamine) dendrimers (G4-PAMAM-NH 2 ) and fifth generation of poly (propylene) imine dendrimers (G5-PPI-NH 2 ). It was observed that aqueous solubility of BTZ was concentration and pH dependent. At 2 mM G5-PPI-NH 2 concentration, the fold increase in bortezomib solubility was 1152.63 times in water, while approximately 3426.69 folds increase in solubility was observed at pH 10.0, respectively (p < 0.05). The solubility of the drug was increased to a greater extent with G5-PPI-NH 2 dendrimers because it has more hydrophobic interior than G4-PAMAM-NH 2 dendrimers. The release of BTZ from G5-PPI-NH 2 complex was comparatively slower than G4-PAMAM-NH 2 . The thermodynamic treatment of data proved that dendrimer drug complexes were stable at all pH with values of ΔG always negative. The experimental findings were also proven by molecular simulation studies and by calculating RMSD and intermolecular hydrogen bonding through Schrodinger software. It was concluded that PPI dendrimers were able to solubilize the drug more effectively than PAMAM dendrimers through electrostatic interactions. - Highlights: • The present study reports the application of PAMAM and PPI dendrimers in solubilizing bortezomib with possible mechanism. • Improved solubility of bortezomib through dendrimers could significantly contribute its successful anticancer potential. • Molecular simulation and thermodynamic

  6. Clinical applications of gamma delta T cells with multivalent immunity

    Directory of Open Access Journals (Sweden)

    Drew C Deniger

    2014-12-01

    Full Text Available Gamma delta T cells hold promise for adoptive immunotherapy because of their reactivity to bacteria, viruses, and tumors. However, these cells represent a small fraction (1-5% of the peripheral T-cell pool and require activation and propagation to achieve clinical benefit. Aminobisphosphonates specifically expand the Vgamma9Vdelta2 subset of gamma delta T cells and have been used in clinical trials of cancer where objective responses were detected. The Vgamma9Vdelta2 TCR heterodimer binds multiple ligands and results in a multivalent attack by a monoclonal T cell population. Alternatively, populations of gamma delta T cells with oligoclonal or polyclonal TCR repertoire could be infused for broad-range specificity. However, this goal has been restricted by a lack of applicable expansion protocols for non-Vgamma9Vdelta2 cells. Recent advances using immobilized antigens, agonistic monoclonal antibodies (mAbs, tumor-derived artificial antigen presenting cells (aAPC, or combinations of activating mAbs and aAPC have been successful in expanding gamma delta T cells with oligoclonal or polyclonal TCR repertoires. Immobilized MHC Class-I chain-related A was a stimulus for gamma delta T cells expressing TCRdelta1 isotypes, and plate-bound activating antibodies have expanded Vdelta1 and Vdelta2 cells ex vivo. Clinically-sufficient quantities of TCRdelta1, TCRdelta2, and TCRdelta1negTCRdelta2neg have been produced following co-culture on aAPC, and these subsets displayed differences in memory phenotype and reactivity to tumors in vitro and in vivo. Gamma delta T cells are also amenable to genetic modification as evidenced by introduction of alpha beta TCRs, chimeric antigen receptors (CARs, and drug-resistance genes. This represents a promising future for the clinical application of oligoclonal or polyclonal gamma delta T cells in autologous and allogeneic settings that builds on current trials testing the safety and efficacy of Vgamma9Vdelta2 T cells.

  7. Oligothia dendrimers for the formation of gold nanoparticles

    NARCIS (Netherlands)

    d'Aleo, A.; Williams, R.M.; Osswald, F.; Edamana, P.; Hahn, U.; van Heyst, J.; Tichelaar, F.D.; Voegtle, F.; De Cola, L.

    2004-01-01

    The synthesis and characterization of oligothia dendrimers and their use for the formation of gold nanoparticles is described. The role played by these dendrimers in controlling the stability and size of the particles is discussed. It is shown that the generation of the dendrimers, as well as the

  8. Preliminary biological evaluation of a urea-functionalized dendrimer

    International Nuclear Information System (INIS)

    Stephan, H.; Syhre, R.; Spies, H.; Johannsen, B.; Zessin, J.; Steinbach, J.; Klein, L.; Werner, N.; Voegtle, F.

    2002-01-01

    A new third generation ethylurea-functionalized polypropyleneamine dendrimer was prepared. After labelling this dendrimer with 11-carbon the biodistribution in rats was studied. The highest level of radioactivity was found in the liver (30-35% ID). The 11 C-labelled dendrimer was well tolerated by the rats. (orig.)

  9. Polypropyleneimine and polyamidoamine dendrimer mediated enhanced solubilization of bortezomib: Comparison and evaluation of mechanistic aspects by thermodynamics and molecular simulations.

    Science.gov (United States)

    Chaudhary, Sonam; Gothwal, Avinash; Khan, Iliyas; Srivastava, Shubham; Malik, Ruchi; Gupta, Umesh

    2017-03-01

    Bortezomib (BTZ) is the first proteasome inhibitor approved by the US-FDA is majorly used for the treatment of newly diagnosed and relapsed multiple myeloma including mantle cell lymphoma. BTZ is hydrophobic in nature and is a major cause for its minimal presence as marketed formulations. The present study reports the design, development and characterization of dendrimer based formulation for the improved solubility and effectivity of bortezomib. The study also equally focuses on the mechanistic elucidation of solubilization by two types of dendrimers i.e. fourth generation of poly (amidoamine) dendrimers (G4-PAMAM-NH 2 ) and fifth generation of poly (propylene) imine dendrimers (G5-PPI-NH 2 ). It was observed that aqueous solubility of BTZ was concentration and pH dependent. At 2mM G5-PPI-NH 2 concentration, the fold increase in bortezomib solubility was 1152.63 times in water, while approximately 3426.69 folds increase in solubility was observed at pH10.0, respectively (pdendrimers because it has more hydrophobic interior than G4-PAMAM-NH 2 dendrimers. The release of BTZ from G5-PPI-NH 2 complex was comparatively slower than G4-PAMAM-NH 2 . The thermodynamic treatment of data proved that dendrimer drug complexes were stable at all pH with values of ΔG always negative. The experimental findings were also proven by molecular simulation studies and by calculating RMSD and intermolecular hydrogen bonding through Schrodinger software. It was concluded that PPI dendrimers were able to solubilize the drug more effectively than PAMAM dendrimers through electrostatic interactions. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Elucidation of the Interaction Mechanism with Liposomes of gH625-Peptide Functionalized Dendrimers

    Science.gov (United States)

    Falanga, Annarita; Tarallo, Rossella; Carberry, Thomas; Galdiero, Massimiliano; Weck, Marcus; Galdiero, Stefania

    2014-01-01

    We have demonstrated that amide-based dendrimers functionalized with the membrane-interacting peptide gH625 derived from the herpes simplex virus type 1 (HSV-1) envelope glycoprotein H enter cells mainly through a non-active translocation mechanism. Herein, we investigate the interaction between the peptide-functionalized dendrimer and liposomes composed of PC/Chol using fluorescence spectroscopy, isothermal titration calorimetry, and surface plasmon resonance to get insights into the mechanism of internalization. The affinity for the membrane bilayer is very high and the interaction between the peptide-dendrimer and liposomes took place without evidence of pore formation. These results suggest that the presented peptidodendrimeric scaffold may be a promising material for efficient drug delivery. PMID:25423477

  11. Recent advances in dendrimer-based nanovectors for tumor-targeted drug and gene delivery

    Science.gov (United States)

    Kesharwani, Prashant; Iyer, Arun K.

    2015-01-01

    Advances in the application of nanotechnology in medicine have given rise to multifunctional smart nanocarriers that can be engineered with tunable physicochemical characteristics to deliver one or more therapeutic agent(s) safely and selectively to cancer cells, including intracellular organelle-specific targeting. Dendrimers having properties resembling biomolecules, with well-defined 3D nanopolymeric architectures, are emerging as a highly attractive class of drug and gene delivery vector. The presence of numerous peripheral functional groups on hyperbranched dendrimers affords efficient conjugation of targeting ligands and biomarkers that can recognize and bind to receptors overexpressed on cancer cells for tumor-cell-specific delivery. The present review compiles the recent advances in dendrimer-mediated drug and gene delivery to tumors by passive and active targeting principles with illustrative examples. PMID:25555748

  12. Adsorption of mixtures of poly(amidoamine) dendrimers and sodium dodecyl sulfate at the air-water interface.

    Science.gov (United States)

    Arteta, Marianna Yanez; Campbell, Richard A; Nylander, Tommy

    2014-05-27

    We relate the adsorption from mixtures of well-defined poly(amidoamine) (PAMAM) dendrimers of generations 4 and 8 with sodium dodecyl sulfate (SDS) at the air-water interface to the bulk solution properties. The anionic surfactant shows strong attractive interactions with the cationic dendrimers at pH 7, and electrophoretic mobility measurements indicate that the association is primarily driven by electrostatic interactions. Optical density measurements highlight the lack of colloidal stability of the formed bulk aggregates at compositions close to charge neutrality, the time scale of which is dependent on the dendrimer generation. Adsorption at the air-water interface was followed from samples immediately after mixing using a combination of surface tension, neutron reflectometry, and ellipsometry measurements. In the phase separation region for dendrimers of generation 4, we observed high surface tension corresponding to a depleted surfactant solution but only when the aggregates carried an excess of surfactant. Interestingly, these depleted adsorption layers contained spontaneously adsorbed macroscopic aggregates, and these embedded particles do not rearrange to spread monomeric material at the interface. These findings are discussed in relation to the interfacial properties of mixtures involving dendrimers of generation 8 as well as polydisperse linear and hyperbranched polyelectrolytes where there is polyelectrolyte bound to a surfactant monolayer. The results presented here demonstrate the capability of dendrimers to sequester anionic surfactants in a controllable manner, with potential applications as demulsification and antifoaming agents.

  13. Toxicity of PAMAM dendrimers to Chlamydomonas reinhardtii

    Energy Technology Data Exchange (ETDEWEB)

    Petit, Anne-Noelle, E-mail: anne-noelle.petit@ec.gc.ca [Environment Canada, 105 McGill Street, Montreal, Quebec H2Y 2E7 (Canada); Eullaffroy, Philippe [Laboratoire Plantes, Pesticides et Developpement Durable, EA 2069, URVVC, BP 1039, Universite de Reims Champagne-Ardenne, 51687 Reims Cedex 2 (France); Debenest, Timothee; Gagne, Francois [Environment Canada, 105 McGill Street, Montreal, Quebec H2Y 2E7 (Canada)

    2010-10-15

    In recent decades, a new class of polymeric materials, PAMAM dendrimers, has attracted marked interest owing to their unique nanoscopic architecture and their hopeful perspectives in nanomedicine and therapeutics. However, the potential release of dendrimers into the aquatic environment raises the issue about their toxicity on aquatic organisms. Our investigation sought to estimate the toxicity of cationic PAMAM dendrimers on the green alga, Chlamydomonas reinhardtii. Algal cultures were exposed to different concentrations (0.3-10 mg L{sup -1}) of low dendrimer generations (G2, G4 and G5) for 72 h. Potential adverse effects on Chlamydomonas were assessed using esterase activity (cell viability), photosynthetic O{sub 2} evolution, pigments content and chlorophyll a fluorescence transient. According to the median inhibitory concentration (IC{sub 50}) appraised from esterase activity, toxicity on cell viability decreased with dendrimer generation number (2, 3 and 5 mg L{sup -1} for G2, G4 and G5 dendrimers, respectively). Moreover, the three generations of dendrimers did not induce the same changes in the photosynthetic metabolism of the green alga. O{sub 2} evolution was stimulated in cultures exposed to the lowest generations tested (i.e. G2 and G4) whereas no significant effects were observed with G5. In addition, total chlorophyll content was increased after G2 treatment at 2.5 mg L{sup -1}. Finally, G2 and G4 had positive effects on photosystem II (PSII): the amount of active PSII reaction centers, the primary charge separation and the electron transport between Q{sub A} and Q{sub B} were all increased inducing activation of the photosynthetic electron transport chain. These changes resulted in stimulation of full photosynthetic performance.

  14. Toxicity of PAMAM dendrimers to Chlamydomonas reinhardtii

    International Nuclear Information System (INIS)

    Petit, Anne-Noelle; Eullaffroy, Philippe; Debenest, Timothee; Gagne, Francois

    2010-01-01

    In recent decades, a new class of polymeric materials, PAMAM dendrimers, has attracted marked interest owing to their unique nanoscopic architecture and their hopeful perspectives in nanomedicine and therapeutics. However, the potential release of dendrimers into the aquatic environment raises the issue about their toxicity on aquatic organisms. Our investigation sought to estimate the toxicity of cationic PAMAM dendrimers on the green alga, Chlamydomonas reinhardtii. Algal cultures were exposed to different concentrations (0.3-10 mg L -1 ) of low dendrimer generations (G2, G4 and G5) for 72 h. Potential adverse effects on Chlamydomonas were assessed using esterase activity (cell viability), photosynthetic O 2 evolution, pigments content and chlorophyll a fluorescence transient. According to the median inhibitory concentration (IC 50 ) appraised from esterase activity, toxicity on cell viability decreased with dendrimer generation number (2, 3 and 5 mg L -1 for G2, G4 and G5 dendrimers, respectively). Moreover, the three generations of dendrimers did not induce the same changes in the photosynthetic metabolism of the green alga. O 2 evolution was stimulated in cultures exposed to the lowest generations tested (i.e. G2 and G4) whereas no significant effects were observed with G5. In addition, total chlorophyll content was increased after G2 treatment at 2.5 mg L -1 . Finally, G2 and G4 had positive effects on photosystem II (PSII): the amount of active PSII reaction centers, the primary charge separation and the electron transport between Q A and Q B were all increased inducing activation of the photosynthetic electron transport chain. These changes resulted in stimulation of full photosynthetic performance.

  15. Dendrimers bind antioxidant polyphenols and cisplatin drug.

    Directory of Open Access Journals (Sweden)

    Amine Abderrezak

    Full Text Available Synthetic polymers of a specific shape and size play major role in drug delivery systems. Dendrimers are unique synthetic macromolecules of nanometer dimensions with a highly branched structure and globular shape with potential applications in gene and drug delivery. We examine the interaction of several dendrimers of different compositions mPEG-PAMAM (G3, mPEG-PAMAM (G4 and PAMAM (G4 with hydrophilic and hydrophobic drugs cisplatin, resveratrol, genistein and curcumin at physiological conditions. FTIR and UV-visible spectroscopic methods as well as molecular modeling were used to analyse drug binding mode, the binding constant and the effects of drug complexation on dendrimer stability and conformation. Structural analysis showed that cisplatin binds dendrimers in hydrophilic mode via Pt cation and polymer terminal NH(2 groups, while curcumin, genistein and resveratrol are located mainly in the cavities binding through both hydrophobic and hydrophilic contacts. The overall binding constants of durg-dendrimers are ranging from 10(2 M(-1 to 10(3 M(-1. The affinity of dendrimer binding was PAMAM-G4>mPEG-PAMAM-G4>mPEG-PAMAM-G3, while the order of drug-polymer stability was curcumin>cisplatin>genistein>resveratrol. Molecular modeling showed larger stability for genisten-PAMAM-G4 (ΔG = -4.75 kcal/mol than curcumin-PAMAM-G4 ((ΔG = -4.53 kcal/mol and resveratrol-PAMAM-G4 ((ΔG = -4.39 kcal/mol. Dendrimers might act as carriers to transport hydrophobic and hydrophilic drugs.

  16. Temperature-sensitive elastin-mimetic dendrimers: Effect of peptide length and dendrimer generation to temperature sensitivity.

    Science.gov (United States)

    Kojima, Chie; Irie, Kotaro; Tada, Tomoko; Tanaka, Naoki

    2014-06-01

    Dendrimers are synthetic macromolecules with unique structure, which are a potential scaffold for peptides. Elastin is one of the main components of extracellular matrix and a temperature-sensitive biomacromolecule. Previously, Val-Pro-Gly-Val-Gly peptides have been conjugated to a dendrimer for designing an elastin-mimetic dendrimer. In this study, various elastin-mimetic dendrimers using different length peptides and different dendrimer generations were synthesized to control the temperature dependency. The elastin-mimetic dendrimers formed β-turn structure by heating, which was similar to the elastin-like peptides. The elastin-mimetic dendrimers exhibited an inverse phase transition, largely depending on the peptide length and slightly depending on the dendrimer generation. The elastin-mimetic dendrimers formed aggregates after the phase transition. The endothermal peak was observed in elastin-mimetic dendrimers with long peptides, but not with short ones. The peptide length and the dendrimer generation are important factors to tune the temperature dependency on the elastin-mimetic dendrimer. Copyright © 2013 Wiley Periodicals, Inc.

  17. Targeted gadolinium-loaded dendrimer nanoparticles for tumor-specific magnetic resonance contrast enhancement

    Directory of Open Access Journals (Sweden)

    Scott D Swanson

    2008-06-01

    Full Text Available Scott D Swanson1, Jolanta F Kukowska-Latallo2, Anil K Patri5, Chunyan Chen6, Song Ge4, Zhengyi Cao3, Alina Kotlyar3, Andrea T East7, James R Baker31Department of Radiology, The University of Michigan Medical School, 2Department of Internal Medicine, The University of Michigan Medical School, 3Michigan Nanotechnology Institute for Medicine and Biological Sciences, The University of Michigan, 4Applied Physics, The University of Michigan, MD, USA; 5Present address: National Cancer Institute at Frederick (Contractor, MD, USA; 6Present address: Intel Corporation, Chandler, AZ, USA; 7Present address: Stritch School of Medicine, Chicago, ILL, USAAbstract: A target-specific MRI contrast agent for tumor cells expressing high affinity folate receptor was synthesized using generation five (G5 of polyamidoamine (PAMAM dendrimer. Surface modified dendrimer was functionalized for targeting with folic acid (FA and the remaining terminal primary amines of the dendrimer were conjugated with the bifunctional NCS-DOTA chelator that forms stable complexes with gadolinium (Gd III. Dendrimer-DOTA conjugates were then complexed with GdCl3, followed by ICP-OES as well as MRI measurement of their longitudinal relaxivity (T1 s−1 mM−1 of water. In xenograft tumors established in immunodeficient (SCID mice with KB human epithelial cancer cells expressing folate receptor (FAR, the 3D MRI results showed specific and statistically significant signal enhancement in tumors generated with targeted Gd(III-DOTA-G5-FA compared with signal generated by non-targeted Gd(III-DOTA-G5 contrast nanoparticle. The targeted dendrimer contrast nanoparticles infiltrated tumor and were retained in tumor cells up to 48 hours post-injection of targeted contrast nanoparticle. The presence of folic acid on the dendrimer resulted in specific delivery of the nanoparticle to tissues and xenograft tumor cells expressing folate receptor in vivo. We present the specificity of the dendrimer

  18. Design, synthesis, and testing of multivalent compounds targeted to melanocortin receptors

    Science.gov (United States)

    Dehigaspitiya, Dilani Chathurika

    Our focus is on developing non-invasive molecular imaging reagents, which target human cancers that presently are difficult to detect, such as melanoma. We wish to apply the multivalency concept to differentiate between healthy cells and melanoma cells. Melanoma cells are known to over-express alpha melanocyte stimulating hormone receptors. A successful multivalent construct should show greater avidity towards melanoma cells than healthy cells due to the synergistic effects arising from multivalency. Both oligomeric and shorter linear constructs bearing the minimum active sequence of melanocyte stimulating hormone, His-DPhe-Arg-Trp-NH2(MSH4), which binds with low micromolar affinity to alpha melanocyte stimulating hormone receptors, were synthesized. Binding affinities of these constructs were evaluated in a competitive binding assay by competing with labeled ligands, Eu-DTPA-PEGO-MSH7 and/or Eu-DTPA-PEGO-NDP-alpha-MSH on the engineered cell line HEK293 CCK2R/hMC4R, which is genetically modified to over-express both the cholecystokinin 2 receptor (CCK2R) and human melanocortin 4 receptor (hMC4R). The oligomers were rapidly assembled using microwave-assisted copper catalyzed azide-alkyne cycloaddition between a dialkyne derivative of MSH4 and a diazide derivative of (Pro-Gly)3 as co-monomers. Three oligomer mixtures were further analyzed based on their degree of oligomerization and the route by which the MSH4 monomers were oligomerized, protected vs deprotected. Completive binding assay against Eu-DTPA-PEGO-MSH7 showed only a statistical enhancement of binding when calculated based on the total MSH4 concentration. However, when the calculation of avidity is based on an estimation of the particles numbers, there was a seven times enhancement of binding compared to a monovalent MSH4 control. The shorter linear multivalent MSH4 constructs were synthesized using ethylene glycol, glycerol, and mannitol as core scaffolds with maximum inter-ligand distances ranging from 27

  19. Tailoring silver nanoparticle construction using dendrimer templated silica networks

    International Nuclear Information System (INIS)

    Liu Xiaojun; Kakkar, Ashok

    2008-01-01

    We have examined the role of the internal environment of dendrimer templated silica networks in tailoring the construction of silver nanoparticle assemblies. Silica networks from which 3,5-dihydroxybenzyl alcohol based dendrimer templates have been completely removed, slowly wet with an aqueous solution of silver acetate. The latter then reacts with internal silica silanol groups, leading to chemisorption of silver ions, followed by the growth of silver oxide nanoparticles. Silica network constructed using generation 4 dendrimer contains residual dendrimer template, and mixes with aqueous silver acetate solution easily. Upon chemisorption, silver ions get photolytically reduced to silver metal under a stabilizing dendrimer environment, leading to the formation of silver metal nanoparticles

  20. PAMAM dendrimer with 4-carbomethoxypyrrolidone - In vitro assessment of neurotoxicity

    DEFF Research Database (Denmark)

    Janaszewska, Anna; Studzian, Maciej; Petersen, Johannes Fabritius

    2015-01-01

    Cytotoxicity of cationic amino-terminated PAMAM dendrimer and modified PAMAM-pyrrolidone dendrimer was compared. LDH assay and cell visualization technique were employed. Mouse embryonic hippocampal cells (mHippoE-18) were used. The experiments were performed in FBS-deprived medium. Pyrrolidone......-modification significantly diminished toxicity of PAMAM dendrimer. The absence of FBS did not reveal significant impact on the toxic effect. Results from LDH assay and MTT test were in good consistency. Low cytotoxicity of PAMAM-pyrrolidone dendrimer increases reliability of the results showing a small impact...... of this dendrimer on cell viability....

  1. Poly(amido amine) dendrimers in oral delivery.

    Science.gov (United States)

    Yellepeddi, Venkata K; Ghandehari, Hamidreza

    2016-01-01

    Poly(amidoamine) (PAMAM) dendrimers have been extensively investigated for oral delivery applications due to their ability to translocate across the gastrointestinal epithelium. In this Review, we highlight recent advances in the evaluation of PAMAM dendrimers as oral drug delivery carriers. Specifically, toxicity, mechanisms of transepithelial transport, models of the intestinal epithelial barrier including isolated human intestinal tissue model, detection of dendrimers, and surface modification are discussed. We also highlight evaluation of various PAMAM dendrimer-drug conjugates for their ability to transport across gastrointestinal epithelium for improved oral bioavailability. In addition, current challenges and future trends for clinical translation of PAMAM dendrimers as carriers for oral delivery are discussed.

  2. Glycodendrimers: tools to explore multivalent galectin-1 interactions

    Directory of Open Access Journals (Sweden)

    Jonathan M. Cousin

    2015-05-01

    Full Text Available Four generations of lactose-functionalized polyamidoamine (PAMAM were employed to further the understanding of multivalent galectin-1 mediated interactions. Dynamic light scattering and fluorescence microscopy were used to study the multivalent interaction of galectin-1 with the glycodendrimers in solution, and glycodendrimers were observed to organize galectin-1 into nanoparticles. In the presence of a large excess of galectin-1, glycodendrimers nucleated galectin-1 into nanoparticles that were remarkably homologous in size (400–500 nm. To understand augmentation of oncologic cellular aggregation by galectin-1, glycodendrimers were used in cell-based assays with human prostate carcinoma cells (DU145. The results revealed that glycodendrimers provided competitive binding sites for galectin-1, which diverted galectin-1 from its typical function in cellular aggregation of DU145 cells.

  3. Bifunctional Phosphorus Dendrimers and Their Properties.

    Science.gov (United States)

    Caminade, Anne-Marie; Majoral, Jean-Pierre

    2016-04-23

    Dendrimers are hyperbranched and monodisperse macromolecules, generally considered as a special class of polymers, but synthesized step-by-step. Most dendrimers have a uniform structure, with a single type of terminal function. However, it is often desirable to have at least two different functional groups. This review will discuss the case of bifunctional phosphorus-containing dendrimers, and the consequences for their properties. Besides the terminal functions, dendritic structures may have also a function at the core, or linked off-center to the core, or at the core of dendrons (dendritic wedges). Association of two dendrons having different terminal functions leads to Janus dendrimers (two faces). The internal structure can also possess functional groups on one layer, or linked to one layer, or on several layers. Finally, there are several ways to have two types of terminal functions, besides the case of Janus dendrimers: either each terminal function bears two functions sequentially, or two different functions are linked to each terminal branching point. Examples of each type of structure will be given in this review, as well as practical uses of such sophisticated structures in the fields of fluorescence, catalysis, nanomaterials and biology.

  4. Emerging concepts in dendrimer-based nanomedicine: from design principles to clinical applications.

    Science.gov (United States)

    Kannan, R M; Nance, E; Kannan, S; Tomalia, D A

    2014-12-01

    Dendrimers are discrete nanostructures/nanoparticles with 'onion skin-like' branched layers. Beginning with a core, these nanostructures grow in concentric layers to produce stepwise increases in size that are similar to the dimensions of many in vivo globular proteins. These branched tree-like concentric layers are referred to as 'generations'. The outer generation of each dendrimer presents a precise number of functional groups that may act as a monodispersed platform for engineering favourable nanoparticle-drug and nanoparticle-tissue interactions. These features have attracted significant attention in medicine as nanocarriers for traditional small drugs, proteins, DNA/RNA and in some instances as intrinsically active nanoscale drugs. Dendrimer-based drugs, as well as diagnostic and imaging agents, are emerging as promising candidates for many nanomedicine applications. First, we will provide a brief survey of recent nanomedicines that are either approved or in the clinical approval process. This will be followed by an introduction to a new 'nanoperiodic' concept which proposes nanoparticle structure control and the engineering of 'critical nanoscale design parameters' (CNDPs) as a strategy for optimizing pharmocokinetics, pharmocodynamics and site-specific targeting of disease. This paradigm has led to the emergence of CNDP-directed nanoperiodic property patterns relating nanoparticle behaviour to critical in vivo clinical translation issues such as cellular uptake, transport, elimination, biodistribution, accumulation and nanotoxicology. With a focus on dendrimers, these CNDP-directed nanoperiodic patterns are used as a strategy for designing and optimizing nanoparticles for a variety of drug delivery and imaging applications, including a recent dendrimer-based theranostic nanodevice for imaging and treating cancer. Several emerging preclinical dendrimer-based nanotherapy concepts related to inflammation, neuro-inflammatory disorders, oncology and infectious

  5. Fluorescent properties of novel dendrimer dyes based on thiazole orange

    International Nuclear Information System (INIS)

    Fei Xuening; Gu Yingchun; Lan Yunquan; Shi Bin

    2011-01-01

    In this paper, polyamidoamine (PAMAM) dendrimers with active amino group of some generations (G=0.5-2) were prepared from commercial aminoacetaldehyde diethyl acetal by the divergent method. After that, thiazole orange (TO) with -COOH was incorporated with dendrimers of G=1 and 2 to afford novel dendrimer-TO dyes. The fluorescent properties studies showed that the fluorescent intensity of the same concentration of dendrimer-TO (G=2) was higher than that of the dendrimer-TO (G=1), and both of them were much stronger than free TO with -COOH. There was a fluorescent enhancement of the dendrimer dyes compared with free dye. The dendrimer dyes were of well-defined chemical structure,with little aggregation and self-quenching as well as good fluorescence properties of good stability, high intensity and sensitivity, which could be used in labeling cancer cells and further in diagnosis and detection of early-stage tumors. - Highlights: → A kind of dendrimer probe based on TO was designed and synthesized. → Dendrimers showed an obvious fluorescence enhancement compared to free dye. → Dendrimers labeled with BSA also showed fluorescence enhancement. → Dendrimers may be used in diagnosis and detection of early-stage tumors.

  6. Interaction between viologen-phosphorus dendrimers and α-synuclein

    International Nuclear Information System (INIS)

    Milowska, Katarzyna; Grochowina, Justyna; Katir, Nadia; El Kadib, Abdelkrim; Majoral, Jean-Pierre; Bryszewska, Maria; Gabryelak, Teresa

    2013-01-01

    In this study the interaction between viologen-phosphorus dendrimers and α-synuclein (ASN) was examined. Polycationic viologen-phosphorus dendrimers (two positive charges per viologen unit) are novel compounds with relatively unknown properties. The influence of these viologen dendrimers on ASN was tested using fluorimetric and circular dichroism methods. ASN contains four tyrosine residues; therefore, the influence of dendrimers on protein molecular conformation by measuring the changes in the ASN fluorescence in the presence of dendrimers was evaluated. The interaction of dendrimers with free L-tyrosine was also monitored. Results show that viologen-phosphorus dendrimers interact with ASN; they quenched the fluorescence of ASN as well as free tyrosine by dynamic and static ways. However, the quenching was not accompanied by modifications in the ASN secondary structure. - Highlights: ► Interaction between viologen-phosphorus dendrimers and α-synuclein (ASN) was investigated. ► Viologen-phosphorus dendrimers can quench the fluorescence of tyrosine in ASN. ► Dendrimers caused red-shift in maximum of fluorescence. ► Viologen-phosphorus dendrimers did not change the secondary structure of ASN.

  7. Brief Timelapse on Dendrimer Chemistry: Advances, Limitations, and Expectations

    KAUST Repository

    Ornelas, Catia

    2015-12-09

    © 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Dendrimers are well-defined branched macromolecules that have been studied for a wide variety of applications. Possibility to add multiple functionalities in precise locations of the dendritic structure generated great expectations for the application of dendrimers in nanomedicine, however, the number of dendrimer-based formulations that advance to clinical studies has been somewhat deceiving. This is partially due to the nonreproducible pharmokinetic behavior observed for multifunctional dendrimers synthesized through the random-statistical approach that leads to mixtures of products. Therefore, it is crucial to develop multifunctional dendrimers with well-defined structures in order to increase the chances of meeting the clinical expectations placed on dendrimers. This talent article will give an overview of the dendrimer field, discussing the application of dendrimers in nanomedicine, light-harvesting systems, sensing and catalysis, with a critical analysis on the expectations, limitations, advances, current challenges and future directions. Dendrimer timelapse demonstrates constant evolution in dendrimer chemistry enabling their application in nanomedicine, protein mimic, catalysis, light harvesting systems, and sensing. Increasing the variety of functionalities in dendrimers located at precise sites of the dendritic backbone result in versatile multifunctional nanomaterials that in the future might approach the conceptual nanobots.

  8. Interaction between viologen-phosphorus dendrimers and {alpha}-synuclein

    Energy Technology Data Exchange (ETDEWEB)

    Milowska, Katarzyna, E-mail: milowska@biol.uni.lodz.pl [Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz (Poland); Grochowina, Justyna [Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz (Poland); Katir, Nadia [Laboratoire de Chimie de Coordination CNRS, 205 route de Narbonne, 31077 Toulouse (France); El Kadib, Abdelkrim [Institute of Nanomaterials and Nanotechnology (INANOTECH)-MAScIR (Moroccan Foundation for Advanced Science, Innovation and Research), ENSET, Avenue de I' Armee Royale, Madinat El Irfane, 10100 Rabat (Morocco); Majoral, Jean-Pierre [Laboratoire de Chimie de Coordination CNRS, 205 route de Narbonne, 31077 Toulouse (France); Bryszewska, Maria; Gabryelak, Teresa [Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz (Poland)

    2013-02-15

    In this study the interaction between viologen-phosphorus dendrimers and {alpha}-synuclein (ASN) was examined. Polycationic viologen-phosphorus dendrimers (two positive charges per viologen unit) are novel compounds with relatively unknown properties. The influence of these viologen dendrimers on ASN was tested using fluorimetric and circular dichroism methods. ASN contains four tyrosine residues; therefore, the influence of dendrimers on protein molecular conformation by measuring the changes in the ASN fluorescence in the presence of dendrimers was evaluated. The interaction of dendrimers with free L-tyrosine was also monitored. Results show that viologen-phosphorus dendrimers interact with ASN; they quenched the fluorescence of ASN as well as free tyrosine by dynamic and static ways. However, the quenching was not accompanied by modifications in the ASN secondary structure. - Highlights: Black-Right-Pointing-Pointer Interaction between viologen-phosphorus dendrimers and {alpha}-synuclein (ASN) was investigated. Black-Right-Pointing-Pointer Viologen-phosphorus dendrimers can quench the fluorescence of tyrosine in ASN. Black-Right-Pointing-Pointer Dendrimers caused red-shift in maximum of fluorescence. Black-Right-Pointing-Pointer Viologen-phosphorus dendrimers did not change the secondary structure of ASN.

  9. Uses of Dendrimers for DNA Microarrays

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Majoral

    2006-08-01

    Full Text Available Biosensors such as DNA microarrays and microchips are gaining an increasingimportance in medicinal, forensic, and environmental analyses. Such devices are based onthe detection of supramolecular interactions called hybridizations that occur betweencomplementary oligonucleotides, one linked to a solid surface (the probe, and the other oneto be analyzed (the target. This paper focuses on the improvements that hyperbranched andperfectly defined nanomolecules called dendrimers can provide to this methodology. Twomain uses of dendrimers for such purpose have been described up to now; either thedendrimer is used as linker between the solid surface and the probe oligonucleotide, or thedendrimer is used as a multilabeled entity linked to the target oligonucleotide. In the firstcase the dendrimer generally induces a higher loading of probes and an easier hybridization,due to moving away the solid phase. In the second case the high number of localized labels(generally fluorescent induces an increased sensitivity, allowing the detection of smallquantities of biological entities.

  10. Structural properties of dendrimer-colloid mixtures

    International Nuclear Information System (INIS)

    Lenz, Dominic A; Blaak, Ronald; Likos, Christos N

    2012-01-01

    We consider binary mixtures of colloidal particles and amphiphilic dendrimers of the second generation by means of Monte Carlo simulations. By using the effective interactions between monomer-resolved dendrimers and colloids, we compare the results of simulations of mixtures stemming from a full monomer-resolved description with the effective two-component description at different densities, composition ratios, colloid diameters and interaction strengths. Additionally, we map the two-component system onto an effective one-component model for the colloids in the presence of the dendrimers. Simulations based on the resulting depletion potentials allow us to extend the comparison to yet another level of coarse graining and to examine under which conditions this two-step approach is valid. In addition, a preliminary outlook into the phase behavior of this system is given. (paper)

  11. Simulation of some dynamical aspects of the photophysics of dye molecules encapsulated in a dendrimer

    Energy Technology Data Exchange (ETDEWEB)

    Teobaldi, Gilberto [Dipartimento di Chimica ' G. Ciamician' , Universita di Bologna, Via F. Selmi 2, Bologna I-40126 (Italy); Zerbetto, Francesco [Dipartimento di Chimica ' G. Ciamician' , Universita di Bologna, Via F. Selmi 2, Bologna I-40126 (Italy)]. E-mail: francesco.zerbetto@unibo.it

    2005-03-15

    We use a combination of molecular dynamics and quantum chemical calculations to investigate the photophysics of Eosin Y encapsulated in a fourth generation of poly-propylene amine dendrimer functionalized in the periphery with dansyl units. Once in contact with the macromolecule, the guests display a double exponential decay of the excited states that is reproduced by the present model.

  12. Simulation of some dynamical aspects of the photophysics of dye molecules encapsulated in a dendrimer

    International Nuclear Information System (INIS)

    Teobaldi, Gilberto; Zerbetto, Francesco

    2005-01-01

    We use a combination of molecular dynamics and quantum chemical calculations to investigate the photophysics of Eosin Y encapsulated in a fourth generation of poly-propylene amine dendrimer functionalized in the periphery with dansyl units. Once in contact with the macromolecule, the guests display a double exponential decay of the excited states that is reproduced by the present model

  13. A cyclam core dendrimer containing dansyl and oligoethylene glycol chains in the branches: protonation and metal coordination.

    Science.gov (United States)

    Branchi, Barbara; Ceroni, Paola; Bergamini, Giacomo; Balzani, Vincenzo; Maestri, Mauro; van Heyst, Jeroen; Lee, Sang-Kyu; Luppertz, Friedhelm; Vögtle, Fritz

    2006-12-04

    We have synthesized a dendrimer (1) consisting of a 1,4,8,11-tetraazacyclotetradecane (cyclam) core, appended with four benzyl substituents that carry, in the 3- and 5-positions, a dansyl amide derivative (of type 2), in which the amide hydrogen is replaced by a benzyl unit that carries an oligoethylene glycol chain in the 3- and 5-positions. All together, the dendrimer contains 16 potentially luminescent moieties (eight dansyl- and eight dimethoxybenzene-type units) and three distinct types of multivalent sites that, in principle, can be protonated or coordinated to metal ions (the cyclam nitrogen atoms, the amine moieties of the eight dansyl units, and the 16 oligoethylene glycol chains). We have studied the absorption and luminescence properties of 1, 2, and 3 in acetonitrile and the changes taking place upon titration with acid and a variety of divalent (Co2+, Ni2+, Cu2+, Zn2+), and trivalent (Nd3+, Eu3+, Gd3+) metal ions as triflate and/or nitrate salts. The results obtained show that: 1) double protonation of the cyclam ring takes place before protonation of the dansyl units; 2) the oligoethylene glycol chains do not interfere with protonation of the cyclam core and the dansyl units in the ground state, but affect the luminescence of the protonated dansyl units; 3) the first equivalent of metal ion is coordinated by the cyclam core; 4) the interaction of the resulting cyclam complex with the appended dansyl units depends on the nature of the metal ion; 5) coordination of metal ions by the dansyl units follows at high metal-ion concentrations; 6) the effect of the metal ion depends on the nature of the counterion. This example demonstrates that dendrimers may exhibit complete functionality resulting from the integration of the specific properties of their component units.

  14. Nonlinear Optical and Time-Resolved Properties of Novel Organic Dendrimers and Dendrimer Metal

    National Research Council Canada - National Science Library

    Goodson, T., III

    2004-01-01

    .... We found in particular that gold-metal dendrimer nanocomposites have very strong optical limiting properties that may be useful for eye and sensor protection devices in the visible and near Infrared spectral regions...

  15. Structure of DNA-Functionalized Dendrimer Nanoparticles

    OpenAIRE

    Kumar, Mattaparthi Venkata Satish; Maiti, Prabal K

    2012-01-01

    Atomistic molecular dynamics simulations have been carried out to reveal the characteristic features of ethylenediamine (EDA) cored protonated poly amido amine (PAMAM) dendrimers of generation 3 (G3) and 4 (G4) that are functionalized with single stranded DNAs (ssDNAs). The four ssDNA strands that are attached via alkythiolate [-S (CH2)6-] linker molecule to the free amine groups on the surface of the PAMAM dendrimers observed to undergo a rapid conformational change during the 25 ns long sim...

  16. Proof of concept of a "greener" protein purification/enrichment method based on carboxylate-terminated carbosilane dendrimer-protein interactions.

    Science.gov (United States)

    González-García, Estefanía; Maly, Marek; de la Mata, Francisco Javier; Gómez, Rafael; Marina, María Luisa; García, María Concepción

    2016-11-01

    Protein sample preparation is a critical and an unsustainable step since it involves the use of tedious methods that usually require high amount of solvents. The development of new materials offers additional opportunities in protein sample preparation. This work explores, for the first time, the potential application of carboxylate-terminated carbosilane dendrimers to the purification/enrichment of proteins. Studies on dendrimer binding to proteins, based on protein fluorescence intensity and emission wavelengths measurements, demonstrated the interaction between carboxylate-terminated carbosilane dendrimers and proteins at all tested pH levels. Interactions were greatly affected by the protein itself, pH, and dendrimer concentration and generation. Especially interesting was the interaction at acidic pH since it resulted in a significant protein precipitation. Dendrimer-protein interactions were modeled observing stable complexes for all proteins. Carboxylate-terminated carbosilane dendrimers at acidic pH were successfully used in the purification/enrichment of proteins extracted from a complex sample. Graphical Abstract Images showing the growing turbidity of solutions containing a mixture of proteins (lysozyme, myoglobin, and BSA) at different protein:dendrimer ratios (1:0, 1:1, 1:8, and 1:20) at acidic pH and SDS-PAGE profiles of the corresponsing supernatants. Comparison of SDS-PAGE profiles for the pellets obtained during the purification of proteins present in a complex sample using a conventional "no-clean" method based on acetone precipitation and the proposed "greener" method using carboxylate-terminated carbosilane dendrimer at a 1:20 protein:dendrimer ratio.

  17. Antibody-dendrimer conjugates: the number, not the size of the dendrimers, determines the immunoreactivity.

    Science.gov (United States)

    Wängler, C; Moldenhauer, G; Eisenhut, M; Haberkorn, U; Mier, W

    2008-04-01

    Radioimmunotherapy using antibodies with favorable tumor targeting properties and high binding affinity is increasingly applied in cancer therapy. The potential of this valuable cancer treatment modality could be further improved by increasing the specific activity of the labeled proteins. This can be done either by coupling a large number of chelators which leads to a decreased immunoreactivity or by conjugating a small number of multimeric chelators. In order to systematically investigate the influence of conjugations on immunoreactivity with respect to size and number of the conjugates, the anti-EGFR antibody hMAb425 was reacted with PAMAM dendrimers of different size containing up to 128 chelating agents per conjugation site. An improved dendrimer synthesis protocol was established to obtain compounds of high homogeneity suitable for the formation of defined protein conjugates. The quantitative derivatization of the PAMAM dendrimers with DOTA moieties and the characterization of the products by isotopic dilution titration using (111)In/(nat)In are shown. The DOTA-containing dendrimers were conjugated with high efficiency to hMAb425 by applying Sulfo-SMCC as cross-linking agent and a 10- to 25-fold excess of the thiol-containing dendrimers. The determination of the immunoreactivities of the antibody-dendrimer conjugates by FACS analysis revealed a median retained immunoreactivity of 62.3% for 1.7 derivatization sites per antibody molecule, 55.4% for 2.8, 27.9% for 5.3, and 17.1% for 10.0 derivatization sites per antibody but no significant differences in immunoreactivity for different dendrimer sizes. These results show that the dendrimer size does not influence the immunoreactivity of the derivatized antibody significantly over a wide molecular weight range, whereas the number of derivatization sites has a crucial effect.

  18. Increase in Dye:Dendrimer Ratio Decreases Cellular Uptake of Neutral Dendrimers in RAW Cells.

    Science.gov (United States)

    Vaidyanathan, Sriram; Kaushik, Milan; Dougherty, Casey; Rattan, Rahul; Goonewardena, Sascha N; Banaszak Holl, Mark M; Monano, Janet; DiMaggio, Stassi

    2016-09-12

    Neutral generation 3 poly(amidoamine) dendrimers were labeled with Oregon Green 488 (G3-OG n ) to obtain materials with controlled fluorophore:dendrimer ratios (n = 1-2), a mixture containing mostly 3 dyes per dendrimer, a mixture containing primarily 4 or more dyes per dendrimer ( n = 4+), and a stochastic mixture ( n = 4 avg ). The UV absorbance of the dye conjugates increased linearly as n increased and the fluorescence emission decreased linearly as n increased. Cellular uptake was studied in RAW cells and HEK 293A cells as a function of the fluorophore:dendrimer ratio (n). The cellular uptake of G3-OG n ( n = 3, 4+, 4 avg ) into RAW cells was significantly lower than G3-OG n ( n = 1, 2). The uptake of G3-OG n ( n = 3, 4+, 4 avg ) into HEK 293A cells was not significantly different from G3-OG 1 . Thus, the fluorophore:dendrimer ratio was observed to change the extent of uptake in the macrophage uptake mechanism but not in the HEK 293A cell. This difference in endocytosis indicates the presence of a pathway in the macrophage that is sensitive to hydrophobicity of the particle.

  19. Practical computational toolkits for dendrimers and dendrons structure design

    Science.gov (United States)

    Martinho, Nuno; Silva, Liana C.; Florindo, Helena F.; Brocchini, Steve; Barata, Teresa; Zloh, Mire

    2017-09-01

    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.

  20. Generation dependent cancer targeting potential of poly(propyleneimine) dendrimer.

    Science.gov (United States)

    Kesharwani, Prashant; Tekade, Rakesh K; Jain, Narendra K

    2014-07-01

    Dendrimer-mediated delivery of bioactive is a successful and widely explored concept. This paper desribes comparative data pertaining to generation dependent cancer targeting propensity of Poly(propyleneimine) (PPI) dendrimers. This debut report reportsthe drug targeting and antciancer potential of different dendrimer generations. PPI dendrimers of different generations (3.0G, 4.0G and 5.0G) were synthesized and loaded with Melphalan. Results from loading, hemolysis, hematologic, cytotoxicty and flow cytometry assay depicted that as the generation of dendrimer increased from fourth to fifth, the only parameter i.e. toxicty is increased exponentionally. However, others parameters, i.e. loading, sustained release behavior, and targeting efficacy increased negligibly. Kaplan-Meier survival curves clearly depicted comparable therapeutic potential of PPI4M with PPI5M. In vivo investigations in Balb/c mice again favored 4.0G PPI dendrimer to be preferable nanocarrier for anticancer drug delivery owing to analogous anticancer potential. The outcomes of the investigation evidently projects 4.0G PPI dendrimer over 3.0G and 5.0G dendrimer in respect of its drug delivery benefit as well as superior biocompatibility. Thus, much against the common belief, 4.0G PPI dendrimers may be considered to be optimum in respect of drug delivery precluding the use of much more toxic 5.0G PPI dendrimer, which offers no benefit over 4.0G. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Nature of the effective interaction between dendrimers

    International Nuclear Information System (INIS)

    Mandal, Taraknath; Dasgupta, Chandan; Maiti, Prabal K.

    2014-01-01

    We have performed fully atomistic classical molecular dynamics simulations to calculate the effective interaction between two polyamidoamine dendrimers. Using the umbrella sampling technique, we have obtained the potential of mean force (PMF) between the dendrimers and investigated the effects of protonation level and dendrimer size on the PMF. Our results show that the interaction between the dendrimers can be tuned from purely repulsive to partly attractive by changing the protonation level. The PMF profiles are well-fitted by the sum of an exponential and a Gaussian function with the weight of the exponential function dominating over that of the Gaussian function. This observation is in disagreement with the results obtained in previous analytic [C. Likos, M. Schmidt, H. Löwen, M. Ballauff, D. Pötschke, and P. Lindner, Macromolecules 34, 2914 (2001)] and coarse-grained simulation [I. Götze, H. Harreis, and C. Likos, J. Chem. Phys. 120, 7761 (2004)] studies which predicted the effective interaction to be Gaussian

  2. Nature of the effective interaction between dendrimers

    Energy Technology Data Exchange (ETDEWEB)

    Mandal, Taraknath, E-mail: taraknath@physics.iisc.ernet.in; Dasgupta, Chandan, E-mail: cdgupta@physics.iisc.ernet.in; Maiti, Prabal K., E-mail: maiti@physics.iisc.ernet.in [Centre for Condensed Matter Theory, Physics Department, Indian Institute of Science, Bangalore-560012 (India)

    2014-10-14

    We have performed fully atomistic classical molecular dynamics simulations to calculate the effective interaction between two polyamidoamine dendrimers. Using the umbrella sampling technique, we have obtained the potential of mean force (PMF) between the dendrimers and investigated the effects of protonation level and dendrimer size on the PMF. Our results show that the interaction between the dendrimers can be tuned from purely repulsive to partly attractive by changing the protonation level. The PMF profiles are well-fitted by the sum of an exponential and a Gaussian function with the weight of the exponential function dominating over that of the Gaussian function. This observation is in disagreement with the results obtained in previous analytic [C. Likos, M. Schmidt, H. Löwen, M. Ballauff, D. Pötschke, and P. Lindner, Macromolecules 34, 2914 (2001)] and coarse-grained simulation [I. Götze, H. Harreis, and C. Likos, J. Chem. Phys. 120, 7761 (2004)] studies which predicted the effective interaction to be Gaussian.

  3. Fluorescent Self-Assembled Polyphenylene Dendrimer Nanofibers

    NARCIS (Netherlands)

    Liu, Daojun; Feyter, Steven De; Cotlet, Mircea; Wiesler, Uwe-Martin; Weil, Tanja; Herrmann, Andreas; Müllen, Klaus; Schryver, Frans C. De

    2003-01-01

    A second-generation polyphenylene dendrimer 1 self-assembles into nanofibers on various substrates such as HOPG, silicon, glass, and mica from different solvents. The investigation with noncontact atomic force microscopy (NCAFM) and scanning electron microscopy (SEM) shows that the morphology of the

  4. Dendrimer-coupled sonophoresis-mediated transdermal drug-delivery system for diclofenac.

    Science.gov (United States)

    Huang, Bin; Dong, Wei-Jiang; Yang, Gao-Yi; Wang, Wei; Ji, Cong-Hua; Zhou, Fei-Ni

    2015-01-01

    The purpose of the present study was to develop a novel transdermal drug-delivery system comprising a polyamidoamine dendrimer coupled with sonophoresis to enhance the permeation of diclofenac (DF) through the skin. The novel transdermal drug-delivery system was developed by using a statistical Plackett-Burman design. Hairless male Wistar rat skin was used for the DF-permeation study. Coupling media concentration, ultrasound-application time, duty cycle, distance from probe to skin, and a third-generation polyamidoamine-dendrimer concentration were selected as independent variables, while in vitro drug release was selected as a dependent variable. Independent variables were found to be statistically significant (Pdelivery, run 13) showed 56.69 µg/cm(2) cumulative drug permeated through the skin, while the DF-dendrimer gel without sonophoresis treatment (run 14) showed 257.3 µg/cm(2) cumulative drug permeated through the skin after 24 hours. However, when the same gel was applied to sonophoresis-treated skin, drastic permeation enhancement was observed. In the case of run 3, the cumulative drug that permeated through the skin was 935.21 µg/cm(2). It was concluded that dendrimer-coupled sonophoresis-mediated transdermal drug delivery system has the potential to enhance the permeation of DF through the skin.

  5. Removal of heavy metal ions from wastewaters using dendrimer-functionalized multi-walled carbon nanotubes.

    Science.gov (United States)

    Iannazzo, Daniela; Pistone, Alessandro; Ziccarelli, Ida; Espro, Claudia; Galvagno, Signorino; Giofré, Salvatore V; Romeo, Roberto; Cicero, Nicola; Bua, Giuseppe D; Lanza, Giuseppe; Legnani, Laura; Chiacchio, Maria A

    2017-06-01

    Dendrimer-functionalized multi-walled carbon nanotubes (MWCNT) for heavy metal ion removal from wastewaters were developed. Triazole dendrimers (TD) were built directly onto the carbon nanotube surface by successive click chemistry reactions affording the zero- and first-generation dendrimer-functionalized MWCNT (MWCNT-TD1 and MWCNT-TD2). The Moedritzer-Irani reaction carried out on the amino groups present on the MWCNT-TD2 sample gave the corresponding α-aminophosphonate nanosystem MWCNT-TD2P. Both MWCNT-TD2 and MWCNT-TD2P nanosystems have been characterized by physical, chemical, and morphological analyses. Their chelating abilities towards the toxic metal ions Pb 2+ , Hg 2+ , and Ni 2+ and the harmless Ca 2+ ion have been experimentally evaluated in the two different sets of experiments and at the salt concentrations of 1 mg/mL or 1 μg/mL by inductively coupled plasma mass spectrometry (ICP-MS). The results of these studies pointed out the interesting chelating behavior for the phosphonated nanosystem towards the Hg 2+ ion. The complexation mode of the best chelating system MWCNT-TD2P with mercury was investigated through density functional theory (DFT) calculations, suggesting a chelation mechanism involving the two oxygen atoms of the phosphate group. The synthesized dendrimers, supported on the multi-walled carbon nanotubes, have shown the potential to be used for the selective toxic metal ion removal and recovery.

  6. PAMAM dendrimers and graphene: materials for removing aromatic contaminants from water.

    Science.gov (United States)

    DeFever, Ryan S; Geitner, Nicholas K; Bhattacharya, Priyanka; Ding, Feng; Ke, Pu Chun; Sarupria, Sapna

    2015-04-07

    We present results from experiments and atomistic molecular dynamics simulations on the remediation of naphthalene by polyamidoamine (PAMAM) dendrimers and graphene oxide (GrO). Specifically, we investigate 3rd-6th generation (G3-G6) PAMAM dendrimers and GrO with different levels of oxidation. The work is motivated by the potential applications of these emerging nanomaterials in removing polycyclic aromatic hydrocarbon contaminants from water. Our experimental results indicate that GrO outperforms dendrimers in removing naphthalene from water. Molecular dynamics simulations suggest that the prominent factors driving naphthalene association to these seemingly disparate materials are similar. Interestingly, we find that cooperative interactions between the naphthalene molecules play a significant role in enhancing their association to the dendrimers and GrO. Our findings highlight that while selection of appropriate materials is important, the interactions between the contaminants themselves can also be important in governing the effectiveness of a given material. The combined use of experiments and molecular dynamics simulations allows us to comment on the possible factors resulting in better performance of GrO in removing polyaromatic contaminants from water.

  7. Effects of solute-solute interactions on protein stability studied using various counterions and dendrimers.

    Directory of Open Access Journals (Sweden)

    Curtiss P Schneider

    Full Text Available Much work has been performed on understanding the effects of additives on protein thermodynamics and degradation kinetics, in particular addressing the Hofmeister series and other broad empirical phenomena. Little attention, however, has been paid to the effect of additive-additive interactions on proteins. Our group and others have recently shown that such interactions can actually govern protein events, such as aggregation. Here we use dendrimers, which have the advantage that both size and surface chemical groups can be changed and therein studied independently. Dendrimers are a relatively new and broad class of materials which have been demonstrated useful in biological and therapeutic applications, such as drug delivery, perturbing amyloid formation, etc. Guanidinium modified dendrimers pose an interesting case given that guanidinium can form multiple attractive hydrogen bonds with either a protein surface or other components in solution, such as hydrogen bond accepting counterions. Here we present a study which shows that the behavior of such macromolecule species (modified PAMAM dendrimers is governed by intra-solvent interactions. Attractive guanidinium-anion interactions seem to cause clustering in solution, which inhibits cooperative binding to the protein surface but at the same time, significantly suppresses nonnative aggregation.

  8. A polyamidoamine dendrimer-streptavidin supramolecular architecture for biosensor development.

    Science.gov (United States)

    Soda, N; Arotiba, O A

    2017-12-01

    A novel polyamidoamine dendrimer-streptavidin supramolecular architecture suitable as a versatile platform for biosensor development is reported. The dendrimer was electrodeposited on a glassy carbon electrode via cyclic voltammetry. The dendrimer electrode was further modified with streptavidin by electrostatic attraction upon drop coating. The platform i.e. the dendrimer-streptavidin modified electrode was electrochemically interrogated in phosphate buffer, ferrocyanide and H 2 O 2 . The dendrimer-streptavidin platform was used in the preparation of a simple DNA biosensor as a proof of concept. The supramolecular architecture of dendrimer-streptavidin was stable, electroactive and thus lends itself as a versatile immobilisation layer for any biotinylated bioreceptors in biosensor development. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. The structure of carbosilane dendrimers of higher generations

    International Nuclear Information System (INIS)

    Rogachev, A.V.; Kuklin, A.I.; Chernyj, A.Yu.; Ozerin, A.N.; Muzafarov, A.M.; Tatarinova, E.A.; Gordelij, V.I.

    2008-01-01

    Using small-angle neutron scattering method, we investigate the structure of carbosilane dendrimers of the ninth generation with a four-function core and butyl terminal groups. It is shown that the dendrimers in question are monodispersive objects having anisometric form. The values of the partial volume and the mean scattering length density are determined with the contrast variation method. The studied dendrimers exhibit the same size and distribution of the scattering length density. It is found that about 20% of the interior dendrimer volume is permeable to a solvent. Performing a Monte Carlo simulation, we reconstruct the spatial distribution of scattering length density over the dendrimers and reveal changing of the excluded volume for different contrasts. The spatial structure features of carbosilane dendrimers of higher generations are discussed

  10. Ligand-Receptor Interaction-Mediated Transmembrane Transport of Dendrimer-like Soft Nanoparticles: Mechanisms and Complicated Diffusive Dynamics.

    Science.gov (United States)

    Liang, Junshi; Chen, Pengyu; Dong, Bojun; Huang, Zihan; Zhao, Kongyin; Yan, Li-Tang

    2016-05-09

    Nearly all nanomedical applications of dendrimer-like soft nanoparticles rely on the functionality of attached ligands. Understanding how the ligands interact with the receptors in cell membrane and its further effect on the cellular uptake of dendrimer-like soft nanoparticles is thereby a key issue for their better application in nanomedicine. However, the essential mechanism and detailed kinetics for the ligand-receptor interaction-mediated transmembrane transport of such unconventional nanoparticles remain poorly elucidated. Here, using coarse-grained simulations, we present the very first study of molecular mechanism and kinetics behaviors for the transmembrane transport of dendrimer-like soft nanoparticles conjugated with ligands. A phase diagram of interaction states is constructed through examining ligand densities and membrane tensions that allows us to identify novel endocytosis mechanisms featured by the direct wrapping and the penetration-extraction vesiculation. The results provide an in-depth insight into the diffusivity of receptors and dendrimer in the membrane plane and demonstrate how the ligand density influences receptor diffusion and uptake kinetics. It is interesting to find that the ligand-conjugated dendrimers present superdiffusive behaviors on a membrane, which is revealed to be driven by the random fluctuation dynamics of the membrane. The findings facilitate our understanding of some recent experimental observations and could establish fundamental principles for the future development of such important nanomaterials for widespread nanomedical applications.

  11. Multivalent weak electrolytes - risky background electrolytes for capillary zone electrophoresis

    Czech Academy of Sciences Publication Activity Database

    Beckers, J. L.; Boček, Petr

    2002-01-01

    Roč. 23, č. 12 (2002), s. 1942-1946 ISSN 0173-0835 R&D Projects: GA ČR GA203/99/0044; GA ČR GA203/02/0023; GA ČR GA203/01/0401; GA AV ČR IAA4031703; GA AV ČR IAA4031103 Institutional research plan: CEZ:AV0Z4031919 Keywords : background electrolytes * capillary zone electrophoresis * multivalent electrolytes Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 4.325, year: 2002

  12. Genetically engineered multivalent single chain antibody constructs for cancer therapy

    International Nuclear Information System (INIS)

    Surinder Batra

    2006-01-01

    compatible with RIT and RIS requirements. For RIT, delivery for sc(Fv)2 and [sc(Fv)2]2 in a fractionated schedule clearly presented a therapeutic advantage over single administration. The treatment group receiving tetravalent scFv showed a statistically significant prolonged survival with both single and fractionated administrations. 99mTc-labeled multivalent scFvs show good tumor targeting characteristics with high radiolocalization indices (tumor:background ratio). Macroautoradiography performed at 6 and 16 h post administration of labeled 99mTc-sc(Fv)2 and 99mTc-[sc(Fv)2] clearly detected the tumors in mice. Humanized scFs showed decreased immunogenicity with patient sera

  13. Dendrimer-encapsulated nanoparticle-core micelles as a modular strategy for particle-in-a-box-in-a-box nanostructures.

    Science.gov (United States)

    Ten Hove, J B; Wang, J; van Leeuwen, F W B; Velders, A H

    2017-12-07

    The hierarchically controlled synthesis and characterization of self-assembling macromolecules and particles are key to explore and exploit new nanomaterials. Here we present a versatile strategy for constructing particle-in-a-box-in-a-box systems by assembling dendrimer-encapsulated gold nanoparticles (DENs) into dendrimicelles. This is realized by combining positively charged PAMAM dendrimers with a negative-neutral block copolymer. The number of particles per dendrimicelle can be controlled by mixing DENs with empty PAMAM dendrimers. The dendrimicelles are stable in solution for months and provide improved resistance for the nanoparticles against degradation. The dendrimicelle strategy provides a flexible platform with a plethora of options for variation in the type of nanoparticles, dendrimers and block copolymers used, and hence is tunable for applications ranging from nanomedicine to catalysis.

  14. A blue-emitting CdS/dendrimer nanocomposite

    International Nuclear Information System (INIS)

    Sooklal, K.; Murphy, C.J.; Hanus, L.H.; Ploehn, H.J.

    1998-01-01

    CdS/dendrimer nanocomposites that emit blue light are formed by the arrested precipitation of nanometer-scale CdS quantum dots in the presence of starburst (poly(aminoamine)) dendrimers as the stabilizing host. The authors report a strong photoluminescence with emission maxima at about 450 nm. The optoelectronic properties of the CdS clusters are shown to be sensitive to synthesis conditions, including dendrimer type, solvent type, and the concentration of dendrimer and other solutes. Thin films of these materials prepared by solution casting retain the optoelectronic properties of the parent solutions. (orig.)

  15. Optical absorption and energy transfer processes in dendrimers

    International Nuclear Information System (INIS)

    Reineker, P.; Engelmann, A.; Yudson, V.I.

    2004-01-01

    For dendrimers of various sizes the energy transfer and the optical absorption is investigated theoretically. The molecular subunits of a dendrimer are modeled as two-level systems. The electronic interaction between them is described via transfer integrals and the influence of vibrational degrees of freedom is taken into account in a first approach using a stochastic model. We discuss the time dependence of the energy transport and show that rim states of the dendrimer dominate the absorption spectra, that in general the electronic excitation energy is concentrated on peripheric molecules, and that the energetically lowest absorption peak is redshifted with increasing dendrimer size due to delocalization of the electronic excitation

  16. Presentations

    International Nuclear Information System (INIS)

    2007-01-01

    The presented materials consist of presentations of international workshop which held in Warsaw from 4 to 5 October 2007. Main subject of the meeting was progress in manufacturing as well as research program development for neutron detector which is planned to be placed at GANIL laboratory and will be used in nuclear spectroscopy research

  17. Structural characterization of new defective molecules in poly(amidoamide) dendrimers by combining mass spectrometry and nuclear magnetic resonance

    Energy Technology Data Exchange (ETDEWEB)

    Tintaru, Aura; Ungaro, Rémi [Aix-Marseille Université – CNRS, UMR 7273, Institut de Chimie Radicalaire, Marseille (France); Liu, Xiaoxiuan; Chen, Chao [Aix-Marseille Université – CNRS, UMR 6114, Centre Interdisciplinaire de Nanosciences de Marseille, Marseille (France); Giordano, Laurent [Aix-Marseille Université – CNRS, UMR 7313, Institut des Sciences Moléculaires de Marseille ISM2 and Ecole Centrale de Marseille, Marseille (France); Peng, Ling [Aix-Marseille Université – CNRS, UMR 6114, Centre Interdisciplinaire de Nanosciences de Marseille, Marseille (France); Charles, Laurence, E-mail: laurence.charles@univ-amu.fr [Aix-Marseille Université – CNRS, UMR 7273, Institut de Chimie Radicalaire, Marseille (France)

    2015-01-01

    Highlights: • ESI-MS/MS and NMR were combined to elucidate a new side-reaction during divergent synthesis of PAMAM dendrimers. • These new impurities exhibit a net gain of a single carbon atom as compared to expected molecules. • The side-reaction is due to formaldehyde, contained as trace level impurity in methanol used as the synthesis medium. - Abstract: A new side-reaction occurring during divergent synthesis of PAMAM dendrimers (generations G{sub 0}–G{sub 2}) was revealed by mass spectrometric detection of defective molecules with a net gain of a single carbon atom as compared to expected compounds. Combining MS/MS experiments performed on different electrosprayed precursor ions (protonated molecules and lithiated adducts) with NMR analyses allowed the origin of these by-products to be elucidated. Modification of one ethylenediamine end-group of perfect dendrimers into a cyclic imidazolidine moiety was induced by formaldehyde present at trace level in the methanol solvent used as the synthesis medium. Dendrimers studied here were purposely constructed from a triethanolamine core to make them more flexible, as compared to NH{sub 3}- or ethylenediamine-core PAMAM, and hence improve their interaction with DNA. Occurrence of this side-reaction would be favored by the particular flexibility of the dendrimer branches.

  18. Synthesis of high generation thermo-sensitive dendrimers for extraction of rivaroxaban from human fluid and pharmaceutic samples.

    Science.gov (United States)

    Parham, Negin; Panahi, Homayon Ahmad; Feizbakhsh, Alireza; Moniri, Elham

    2018-04-13

    In this present study, poly (N-isopropylacrylamide) as a thermo-sensitive agent was grafted onto magnetic nanoparticles, then ethylenediamine and methylmethacrylate were used to synthesize the first generation of poly amidoamine (PAMAM) dendrimers successively and the process continued alternatively until the ten generations of dendrimers. The synthesized nanocomposite was investigated using Fourier transform infrared spectrometry, thermalgravimetry analysis, X-ray diffractometry, elemental analysis and vibrating-sample magnetometer. The particle size and morphology were characterized using dynamic light scattering, field emission scanning electron microscopy and transmission electron microscopy. Batch experiments were conducted to investigate the parameters affecting adsorption and desorption of rivaroxaban by synthesized nanocomposite. The maximum sorption of rivaroxaban by the synthesized nanocomposite was obtained at pH of 8. The resulting grafted magnetic nanoparticle dendrimers were applied for extraction of rivaroxaban from biologic human liquids and medicinal samples. The specifications of rivaroxaban sorbed by a magnetic nanoparticle dendrimer showed good accessibility and high capacity of the active sites within the dendrimers. Urine and drug matrix extraction recoveries of more than 92.5 and 99.8 were obtained, respectively. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Probing multivalency in ligand–receptor-mediated adhesion of soft, biomimetic interfaces

    Directory of Open Access Journals (Sweden)

    Stephan Schmidt

    2015-05-01

    Full Text Available Many biological functions at cell level are mediated by the glycocalyx, a dense carbohydrate-presenting layer. In this layer specific interactions between carbohydrate ligands and protein receptors are formed to control cell–cell recognition, cell adhesion and related processes. The aim of this work is to shed light on the principles of complex formation between surface anchored carbohydrates and receptor surfaces by measuring the specific adhesion between surface bound mannose on a concanavalin A (ConA layer via poly(ethylene glycol-(PEG-based soft colloidal probes (SCPs. Special emphasis is on the dependence of multivalent presentation and density of carbohydrate units on specific adhesion. Consequently, we first present a synthetic strategy that allows for controlled density variation of functional groups on the PEG scaffold using unsaturated carboxylic acids (crotonic acid, acrylic acid, methacrylic acid as grafting units for mannose conjugation. We showed by a range of analytic techniques (ATR–FTIR, Raman microscopy, zeta potential and titration that this synthetic strategy allows for straightforward variation in grafting density and grafting length enabling the controlled presentation of mannose units on the PEG network. Finally we determined the specific adhesion of PEG-network-conjugated mannose units on ConA surfaces as a function of density and grafting type. Remarkably, the results indicated the absence of a molecular-level enhancement of mannose/ConA interaction due to chelate- or subsite-binding. The results seem to support the fact that weak carbohydrate interactions at mechanically flexible interfaces hardly undergo multivalent binding but are simply mediated by the high number of ligand–receptor interactions.

  20. Is a multivalent hand, foot, and mouth disease vaccine feasible?

    Science.gov (United States)

    Klein, Michel; Chong, Pele

    2015-01-01

    Enterovirus A infections are the primary cause of hand, foot and mouth disease (HFMD) in infants and young children. Although enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16) are the predominant causes of HFMD epidemics worldwide, EV-A71 has emerged as a major neurovirulent virus responsible for severe neurological complications and fatal outcomes. HFMD is a serious health threat and economic burden across the Asia-Pacific region. Inactivated EV-A71 vaccines have elicited protection against EV-A71 but not against CV-A16 infections in large efficacy trials. The current development of a bivalent inactivated EV-A71/CV-A16 vaccine is the next step toward that of multivalent HFMD vaccines. These vaccines should ultimately include other prevalent pathogenic coxsackieviruses A (CV-A6 and CV-A10), coxsackieviruses B (B3 and B5) and echovirus 30 that often co-circulate during HFMD epidemics and can cause severe HFMD, aseptic meningitis and acute viral myocarditis. The prospect and challenges for the development of such multivalent vaccines are discussed. PMID:26009802

  1. Dendrimer-conjugated peptide vaccine enhances clearance of Chlamydia trachomatis genital infection.

    Science.gov (United States)

    Ganda, Ingrid S; Zhong, Qian; Hali, Mirabela; Albuquerque, Ricardo L C; Padilha, Francine F; da Rocha, Sandro R P; Whittum-Hudson, Judith A

    2017-07-15

    Peptide-based vaccines have emerged in recent years as promising candidates in the prevention of infectious diseases. However, there are many challenges to maintaining in vivo peptide stability and enhancement of peptide immunogenicity to generate protective immunity which enhances clearance of infections. Here, a dendrimer-based carrier system is proposed for peptide-based vaccine delivery, and shows its anti-microbial feasibility in a mouse model of Chlamydia trachomatis. Chlamydiae are the most prevalent sexually transmitted bacteria worldwide, and also the causal agent of trachoma, the leading cause of preventable infectious blindness. In spite of the prevalence of this infectious agent and the many previous vaccine-related studies, there is no vaccine commercially available. The carrier system proposed consists of generation 4, hydroxyl-terminated, polyamidoamine (PAMAM) dendrimers (G4OH), to which a peptide mimic of a chlamydial glycolipid antigen-Peptide 4 (Pep4, AFPQFRSATLLL) was conjugated through an ester bond. The ester bond between G4OH and Pep4 is expected to break down mainly in the intracellular environment for antigen presentation. Pep4 conjugated to dendrimer induced Chlamydia-specific serum antibodies after subcutaneous immunizations. Further, this new vaccine formulation significantly protected immunized animals from vaginal challenge with infectious Chlamydia trachomatis, and it reduced infectious loads and tissue (genital tract) damage. Pep4 conjugated to G4OH or only mixed with peptide provided enhanced protection compared to Pep4 and adjuvant (i.e. alum), suggesting a potential adjuvant effect of the PAMAM dendrimer. Combined, these results demonstrate that hydroxyl-terminated PAMAM dendrimer is a promising polymeric nanocarrier platform for the delivery of peptide vaccines and this approach has potential to be expanded to other infectious intracellular bacteria and viruses of public health significance. Copyright © 2017 Elsevier B.V. All

  2. Comparison of the internalization of targeted dendrimers and dendrimer-entrapped gold nanoparticles into cancer cells.

    Science.gov (United States)

    Shi, Xiangyang; Wang, Su He; Lee, Inhan; Shen, Mingwu; Baker, James R

    2009-11-01

    Dendrimer-based nanotechnology significantly advances the area of targeted cancer imaging and therapy. Herein, we compared the difference of surface acetylated fluorescein isocyanate (FI) and folic acid (FA) modified generation 5 (G5) poly(amidoamine) dendrimers (G5.NHAc-FI-FA), and dendrimer-entrapped gold nanoparticles with similar modifications ([(Au(0))(51.2)-G5.NHAc-FI-FA]) in terms of their specific internalization to FA receptor (FAR)-overexpressing cancer cells. Confocal microscopic studies show that both G5.NHAc-FI-FA and [(Au(0))(51.2-)G5.NHAc-FI-FA] exhibit similar internalization kinetics regardless of the existence of Au nanoparticles (NPs). Molecular dynamics simulation of the two different nanostructures reveals that the surface area and the FA moiety distribution from the center of the geometry are slightly different. This slight difference may not be recognized by the FARs on the cell membrane, consequently leading to similar internalization kinetics. This study underlines the fact that metal or inorganic NPs entrapped within dendrimers interact with cells in a similar way to that of dendrimers lacking host NPs. 2009 Wiley Periodicals, Inc.

  3. Liquid Crystalline Dendrimers. 1. Synthesis of Five Generations of Carbosilane Liquid Crystalline Dendrimers with Terminal Cyanobiphenyl Groups

    National Research Council Canada - National Science Library

    Shibaev, V

    1998-01-01

    Using the controlled layer by layer experimental technique via reiterative sequence of chemical reactions carbosilane LC dendrimers with terminal cyanobiphenyl mesogenic groups of generations 1 - 5 were synthesized...

  4. New Type of Halogen Bond: Multivalent Halogen Interacting with π- and σ-Electrons

    Directory of Open Access Journals (Sweden)

    Sławomir J. Grabowski

    2017-12-01

    Full Text Available MP2/aug-cc-pVTZ calculations were performed for complexes of BrF3 and BrF5 acting as Lewis acids through the bromine centre, with species playing a role of Lewis base: dihydrogen, acetylene, ethylene, and benzene. The molecular hydrogen donates electrons by its σ-bond, while in remaining moieties—in complexes of hydrocarbons; such an electron transfer follows from π-electrons. The complexes are linked by a kind of the halogen bond that is analyzed for the first time in this study, i.e., it is the link between the multivalent halogen and π or σ-electrons. The nature of such a halogen bond is discussed, as well as various dependencies and correlations are presented. Different approaches are applied here, the Quantum Theory of Atoms in Molecules, Natural Bond Orbital method, the decomposition of the energy of interaction, the analysis of electrostatic potentials, etc.

  5. Host-guest chemistry of dendrimer-drug complexes. 6. Fully acetylated dendrimers as biocompatible drug vehicles using dexamethasone 21-phosphate as a model drug.

    Science.gov (United States)

    Yang, Kun; Weng, Liang; Cheng, Yiyun; Zhang, Hongfeng; Zhang, Jiahai; Wu, Qinglin; Xu, Tongwen

    2011-03-17

    Fully acetylated poly(amidoamine) (PAMAM) dendrimer was proposed as a biocompatible drug vehicle using dexamethasone 21-phosphate (Dp21) as a model drug. NMR techniques including (1)H NMR and 2D NOE NMR were used to characterize the host-guest chemistry of acetylated dendrimer/Dp21 and cationic dendrimer/Dp21 complexes. The pH-dependent micellization, complexation, and inclusion behaviors of Dp21 were observed in the presence of acetylated and cationic PAMAM dendrimers. Acetylated dendrimer only encapsulates Dp21 at acidic conditions, while cationic dendrimer can host Dp21 at both acidic and neutral conditions. The orientation of Dp21 molecules in the dendrimer cavities depends on the quaternization degree of tertiary amine groups of dendrimer and the protonation ratio of phosphate group of Dp21. A distinctive pH-dependent release behavior of Dp21 from the acetylated and nonacetylated dendritic matrix was observed: Dp21 exhibits a much slower release rate from acetylated dendrimer at lower pH conditions and a much faster release rate from nonacetylated dendrimer with decreasing pH values. Cytotoxicity studies further confirmed the biocompatibility of acetylated dendrimers, which are much safer in the delivery of therapeutics for the treatment of various diseases than nonacetylated dendrimers. The dendrimer-drug binding and release mechanisms provide a new insight for the design and optimization of biocompatible dendrimer-based drug delivery systems. © 2011 American Chemical Society

  6. Tailoring the dendrimer core for efficient gene delivery.

    Science.gov (United States)

    Hu, Jingjing; Hu, Ke; Cheng, Yiyun

    2016-04-15

    Dendrimers have been widely used as non-viral gene vectors due to well-defined chemical structures, high density of cationic charges and ease of surface modification. Although a large number of studies have reported the important roles of dendrimer architecture, component, generation and surface functionality in gene delivery, the effect of dendrimer core on this issue still remains unclear. Recent literatures suggest that a slight alternation in dendrimer core has a profound effect in the transfection efficacy and biocompatibility. In this review, we will discuss the transfection mechanism of dendrimers with different types of cores in respect of flexibility, hydrophobicity and functionality. We hope to open a possibility of designing efficient dendrimers for gene delivery by choosing a proper dendrimer core. As a branch of researches on dendrimers and dendritic polymers, the design of biocompatible and high efficient polymeric gene carriers has attracted increasing attentions during these years. Although the effect of dendrimer generation, species, architecture and surface functionality on gene delivery have been widely reported, the effect of dendrimer core on this issue still remains unclear. Recent literatures suggest that a minor variation on the dendrimer core has a profound effect in the transfection efficacy and biocompatibility. This critical review summarized the dendrimers with different types of cores and discussed the transfection mechanism with particular focus on the flexibility, hydrophobicity, and functionality. It is hoped to provide a new insight to design efficient and safe dendrimer-based gene vectors by choosing a proper core. To the best of our knowledge, this is the first review on the effect of dendrimer core on gene delivery. The findings obtained in this filed are of central importance in the design of efficient polymeric gene vectors. This article will appeal a wide readership such as physical chemist, dendrimer chemist, biological

  7. Quaternized Polyamidoamine Dendrimers as Novel Gene Delivery System: Relationship between Degree of Quaternization and Their Influences

    International Nuclear Information System (INIS)

    Lee, Jung Hoon; Lim, Yong beom; Choi, Joon Sig; Choi, Myung Un; Yang, Chul Hak; Park, Jong Sang

    2003-01-01

    Quaternary ammonium groups were introduced to Starburst polyamidoamine (PAMAM) dendrimers for a gene carrier. These quaternary dendritic carriers exhibited reduced cytotoxicity on 293T cells compared to parent dendrimers examined and their transfection efficiency were similar with parent dendrimers. Quaternization could be a promising tool to improve properties of dendrimers as a gene delivery carrier

  8. Presentations

    International Nuclear Information System (INIS)

    2007-01-01

    The PARIS meeting held in Cracow, Poland from 14 to 15 May 2007. The main subjects discussed during this meeting were the status of international project dedicated to gamma spectroscopy research. The scientific research program includes investigations of giant dipole resonance, probe of hot nuclei induced in heavy reactions, Jacobi shape transitions, isospin mixing and nuclear multifragmentation. The mentioned programme needs Rand D development such as new scintillations materials as lanthanum chlorides and bromides as well as new photo detection sensors as avalanche photodiodes - such subjects are also subjects of discussion. Additionally results of computerized simulations of scintillation detectors properties by means of GEANT- 4 code are presented

  9. Dendrimer effects on peptide and protein fibrillation

    DEFF Research Database (Denmark)

    Heegaard, Peter M. H.; Boas, Ulrik; Otzen, Daniel E.

    2007-01-01

    involved in a range of serious and irreversibly progressive pathological conditions (protein-misfolding diseases). Interesting as this may be, the interaction of dendrimers with such generic peptidic aggregates also offers a new perspective on the molecular mechanisms governing assembly and disassembly......, they offer numerous possibilities for interactions with and responses to biological macromolecules and biostructures including cell membranes and proteins. By way of their multiple functional surface groups, they allow the design of surfaces carrying a multitude of biological motifs and/or charges giving...... rise to quite significant biological and physico-chemical effects. Here we describe the surprising ability of dendrimers to interact with and perturb polypeptide conformations, particularly efficiently towards amyloid structures; that is, the structures of highly insoluble polypeptide aggregates...

  10. Presentation

    Directory of Open Access Journals (Sweden)

    Eduardo Vicente

    2013-06-01

    Full Text Available In the present edition of Significação – Scientific Journal for Audiovisual Culture and in the others to follow something new is brought: the presence of thematic dossiers which are to be organized by invited scholars. The appointed subject for the very first one of them was Radio and the invited scholar, Eduardo Vicente, professor at the Graduate Course in Audiovisual and at the Postgraduate Program in Audiovisual Media and Processes of the School of Communication and Arts of the University of São Paulo (ECA-USP. Entitled Radio Beyond Borders the dossier gathers six articles and the intention of reuniting works on the perspectives of usage of such media as much as on the new possibilities of aesthetical experimenting being build up for it, especially considering the new digital technologies and technological convergences. It also intends to present works with original theoretical approach and original reflections able to reset the way we look at what is today already a centennial media. Having broadened the meaning of “beyond borders”, four foreign authors were invited to join the dossier. This is the first time they are being published in this country and so, in all cases, the articles where either written or translated into Portuguese.The dossier begins with “Radio is dead…Long live to the sound”, which is the transcription of a thought provoking lecture given by Armand Balsebre (Autonomous University of Barcelona – one of the most influential authors in the world on the Radio study field. It addresses the challenges such media is to face so that it can become “a new sound media, in the context of a new soundscape or sound-sphere, for the new listeners”. Andrew Dubber (Birmingham City University regarding the challenges posed by a Digital Era argues for a theoretical approach in radio studies which can consider a Media Ecology. The author understands the form and discourse of radio as a negotiation of affordances and

  11. Fluorescent quantum dot hydrophilization with PAMAM dendrimer

    Science.gov (United States)

    Potapkin, Dmitry V.; Geißler, Daniel; Resch-Genger, Ute; Goryacheva, Irina Yu.

    2016-05-01

    Polyamidoamine (PAMAM) dendrimers were used to produce CdSe core/multi-shell fluorescent quantum dots (QDs) which are colloidally stable in aqueous solutions. The size, charge, and optical properties of QDs functionalized with the 4th (G4) and 5th (G5) generation of PAMAM were compared with amphiphilic polymer-covered QDs and used as criteria for the evaluation of the suitability of both water solubilization methods. As revealed by dynamic and electrophoretic light scattering (DLS and ELS), the hydrodynamic sizes of the QDs varied from 30 to 65 nm depending on QD type and dendrimer generation, with all QDs displaying highly positive surface charges, i.e., zeta potentials of around +50 mV in water. PAMAM functionalization yielded stable core/multi-shell QDs with photoluminescence quantum yields ( Φ) of up to 45 %. These dendrimer-covered QDs showed a smaller decrease in their Φ upon phase transfer compared with QDs made water soluble via encapsulation with amphiphilic brush polymer bearing polyoxyethylene/polyoxypropylene chains.

  12. Dendrimer sensors probed with neutron reflectometry

    International Nuclear Information System (INIS)

    Cavaye, Hamish; Smith, Arthur R.G.; Burn, Paul L.; Lo, Shih-Chun; Meredith, Paul; Gentle, Ian R.; James, Michael; Nelson, Andrew

    2009-01-01

    Full text: Oxidative photoluminescence (PL) quenching utilizing conjugated polymers as the sensing has proved to be one of the best of many methods for sensing explosive analytes.[1] However are a number of issues that can make polymers difficult to work with, including complex morphologies reproducibility of syntheses, and the need to include elaborate structures to reduce the packing of the polymer chains. Dendrimers, consisting of a core, dendrons, and surface groups, address these issues by being monodisperse and modular in their design. Determining how analytes are sequestered into thin films is important for solid-state sensors. We show that thin (230 ± 30 A ) and thick (750 ± 50 A) films of a first-generation dendrimer comrised of 2-ethylhexyloxy surface groups, biphenyl-based dendrons, and a 9,9,9',9'-tetra-n-propyl-2,2'-bifluorene core, can rapidly and reversibly detect p-nitrotoll oxidative luminescence quenching. For both the thin and thick films the PL is quenched by just 4 s . Combined PL and neutron reflectometry measurements on pristine and analyte-satura showed that during the adsorption process the films swelled, being on average 4% thicker for thin and thick dendrimer films. At the same time the PL was completely quenched. On removal of the analyte the films returned to their original thickness and scattering length density, and the restored, showing that the sensing process was fully reversible.

  13. Fluorescent quantum dot hydrophilization with PAMAM dendrimer

    Energy Technology Data Exchange (ETDEWEB)

    Potapkin, Dmitry V., E-mail: potapkindv@gmail.com [Saratov State University, Department of General and Inorganic Chemistry, Chemistry Institute (Russian Federation); Geißler, Daniel, E-mail: daniel.geissler@bam.de; Resch-Genger, Ute, E-mail: ute.resch@bam.de [BAM - Federal Institute for Materials Research and Testing (Germany); Goryacheva, Irina Yu., E-mail: goryachevaiy@mail.ru [Saratov State University, Department of General and Inorganic Chemistry, Chemistry Institute (Russian Federation)

    2016-05-15

    Polyamidoamine (PAMAM) dendrimers were used to produce CdSe core/multi-shell fluorescent quantum dots (QDs) which are colloidally stable in aqueous solutions. The size, charge, and optical properties of QDs functionalized with the 4th (G4) and 5th (G5) generation of PAMAM were compared with amphiphilic polymer-covered QDs and used as criteria for the evaluation of the suitability of both water solubilization methods. As revealed by dynamic and electrophoretic light scattering (DLS and ELS), the hydrodynamic sizes of the QDs varied from 30 to 65 nm depending on QD type and dendrimer generation, with all QDs displaying highly positive surface charges, i.e., zeta potentials of around +50 mV in water. PAMAM functionalization yielded stable core/multi-shell QDs with photoluminescence quantum yields (Φ) of up to 45 %. These dendrimer-covered QDs showed a smaller decrease in their Φ upon phase transfer compared with QDs made water soluble via encapsulation with amphiphilic brush polymer bearing polyoxyethylene/polyoxypropylene chains.

  14. Combining metadynamics simulation and experiments to characterize dendrimers in solution

    NARCIS (Netherlands)

    Pavan, G.M.; Barducci, A.; Albertazzi, L.; Parrinello, M.

    2013-01-01

    We report a combined theoretical-experimental approach to characterize dendrimers and Polyethylene Glycol (PEG)-dendrimer hybrids in solution. Well-tempered metadynamics simulation allows for an exhaustive sampling of the conformational fluctuations in solution. In contrast to classical molecular

  15. Composition consisting of a dendrimer and an active substance

    NARCIS (Netherlands)

    1995-01-01

    The invention relates to a composition consisting of a dendrimer provided with blocking agents and an active substance occluded in the dendrimer. According to the invention a blocking agent is a compound which is sterically of sufficient size, which readily enters into a chemical bond with the

  16. Synthesis of PAMAM dendrimers and investigations of their interaction with POPC/POPG lipids

    OpenAIRE

    Gneid, Hassan

    2014-01-01

    PAMAM dendrimers are three dimensional organic polymers synthesised by repetitive steps to achieve a controlled size and shape with a choice of surface functional groups. One of the potential applications of dendrimers is for drug/gene delivery which requires the dendrimer to interact with the cellular membranes. This study is designed to probe the interactions between PAMAM dendrimers and lipid bilayers. To investigate these interactions PAMAM dendrimers up to the third generation were synth...

  17. Dendrimer D5 is a vector for peptide transport to brain cells.

    Science.gov (United States)

    Sarantseva, S V; Bolshakova, O I; Timoshenko, S I; Kolobov, A A; Schwarzman, A L

    2011-02-01

    Dendrimers are a new class of nonviral vectors for gene or drug transport. Dendrimer capacity to penetrate through the blood-brain barrier remaines little studied. Biotinylated polylysine dendrimer D5, similarly to human growth hormone biotinylated fragment covalently bound to D5 dendrimer, penetrates through the blood-brain barrier and accumulates in Drosophila brain after injection into the abdomen. Hence, D5 dendrimer can serve as a vector for peptide transport to brain cells.

  18. Facile Preparation of Hybrid Zinc Porphyrin Dendrimer Using Coordination Complex

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Go-Eun; Shin, Eun Ju [Sunchon National University, Suncheon (Korea, Republic of)

    2016-03-15

    Porphyrins and metalloporphyrins have been investigated extensively due to their important role in natural photosynthesis, strong absorption in visible region, good light-harvesting properties, unique photophysical and electrochemical properties, and the development of simple synthetic routes for various derivatives. Dendrimers have globular structure with branches of repeating units and wide diversity of the architecture because their size, shape, and functionalities can be tailored. Numerous dendrimers have been designed and synthesized for various applications ranging from catalyst to drug delivery. Both pyridine dendrons Py-PD and Py-AD were successfully coordinated at axial position on central zinc metal cation in zinc porphyrin dendrimers ZnP-AD, ZnP-AD2, or ZnP-AD4. Therefore, it was proven that the formation of axial coordination complex between metal-centered dendrimer and ligand-containing dendron provides another facile method for the preparation of new hybrid dendrimer.

  19. Linear scaffolds for multivalent targeting of melanocortin receptors.

    Science.gov (United States)

    Dehigaspitiya, Dilani Chathurika; Anglin, Bobbi L; Smith, Kara R; Weber, Craig S; Lynch, Ronald M; Mash, Eugene A

    2015-12-21

    Molecules bearing one, two, three, or four copies of the tetrapeptide His-dPhe-Arg-Trp were attached to scaffolds based on ethylene glycol, glycerol, and d-mannitol by means of the copper-assisted azide-alkyne cyclization. The abilities of these compounds to block binding of a probe at the melanocortin 4 receptor were evaluated using a competitive binding assay. All of the multivalent molecules studied exhibited 30- to 40-fold higher apparent affinites when compared to a monovalent control. These results are consistent with divalent binding to receptor dimers. No evidence for tri- or tetravalent binding was obtained. Differences in the interligand spacing required for divalent binding, as opposed to tri- or tetravalent binding, may be responsible for these results.

  20. Charge Inversion Effects in Electrophoresis of Polyelectrolytes in the Presence of Multivalent Counterions and Transversal Electric Fields

    Directory of Open Access Journals (Sweden)

    Sorin Nedelcu

    2014-12-01

    Full Text Available By molecular dynamics simulations we investigate the transport of charged polymers in confinement, under externally applied electric fields, in straight cylinders of uniform diameter and in the presence of monovalent or multivalent counterions. The applied electric field has two components; a longitudinal component along the axis of the cylinder and a transversal component perpendicular to the cylinder axis. The direction of electrophoretic velocity depends on the polyelectrolyte length, valency of the counterions present in solution and transversal electric field value. A statistical model is put forward in order to explain these observations.

  1. Light-fuelled transport of large dendrimers and proteins.

    Science.gov (United States)

    Koskela, Jenni E; Liljeström, Ville; Lim, Jongdoo; Simanek, Eric E; Ras, Robin H A; Priimagi, Arri; Kostiainen, Mauri A

    2014-05-14

    This work presents a facile water-based supramolecular approach for light-induced surface patterning. The method is based upon azobenzene-functionalized high-molecular weight triazine dendrimers up to generation 9, demonstrating that even very large globular supramolecular complexes can be made to move in response to light. We also demonstrate light-fuelled macroscopic movements in native biomolecules, showing that complexes of apoferritin protein and azobenzene can effectively form light-induced surface patterns. Fundamentally, the results establish that thin films comprising both flexible and rigid globular particles of large diameter can be moved with light, whereas the presented material concepts offer new possibilities for the yet marginally explored biological applications of azobenzene surface patterning.

  2. Developmental toxicity of low generation PAMAM dendrimers in zebrafish

    International Nuclear Information System (INIS)

    King Heiden, Tisha C.; Dengler, Emelyne; Kao, Weiyuan John; Heideman, Warren; Peterson, Richard E.

    2007-01-01

    Biological molecules and intracellular structures operate at the nanoscale; therefore, development of nanomedicines shows great promise for the treatment of disease by using targeted drug delivery and gene therapies. PAMAM dendrimers, which are highly branched polymers with low polydispersity and high functionality, provide an ideal architecture for construction of effective drug carriers, gene transfer devices and imaging of biological systems. For example, dendrimers bioconjugated with selective ligands such as Arg-Gly-Asp (RGD) would theoretically target cells that contain integrin receptors and show potential for use as drug delivery devices. While RGD-conjugated dendrimers are generally considered not to be cytotoxic, there currently exists little information on the risks that such materials pose to human health. In an effort to compliment and extend the knowledge gleaned from cell culture assays, we have used the zebrafish embryo as a rapid, medium throughput, cost-effective whole-animal model to provide a more comprehensive and predictive developmental toxicity screen for nanomaterials such as PAMAM dendrimers. Using the zebrafish embryo, we have assessed the developmental toxicity of low generation (G3.5 and G4) PAMAM dendrimers, as well as RGD-conjugated forms for comparison. Our results demonstrate that G4 dendrimers, which have amino functional groups, are toxic and attenuate growth and development of zebrafish embryos at sublethal concentrations; however, G3.5 dendrimers, with carboxylic acid terminal functional groups, are not toxic to zebrafish embryos. Furthermore, RGD-conjugated G4 dendrimers are less potent in causing embryo toxicity than G4 dendrimers. RGD-conjugated G3.5 dendrimers do not elicit toxicity at the highest concentrations tested and warrant further study for use as a drug delivery device

  3. An efficient synthesis of D-galactose-based multivalent neoglycoconjugates

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, S.F. de; Souza Filho, J.D. de [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Inst. de Ciencias Exatas. Dept. de Quimica; Alves, Ricardo J., E-mail: ricardodylan@farmacia.ufmg.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Fac. de Farmacia; Figueiredo, Rute C. [Universidade Federal de Ouro Preto (UFOP), MG (Brazil)

    2012-11-15

    In this work, the synthesis of dimeric, trimeric and tetrameric D-galactose-based neoglycoconjugates is reported. The monosaccharide ligand was prepared in 5 straightforward steps from D-galactose using the Doebner modification of the Knoevenagel reaction for chain elongation. The ligand was coupled to 1,4-butanediamine, tris-(2-ethylamino)amine, pentaerythrityltetramine and PAMAM dendrimers (1,4-butanodiamine core G0 and 1,12-dodecanediamine core G0). The unprotected glycodendrimers were purified by size-exclusion chromatography (SEC). This was the only step in which a chromatographic method was employed throughout the synthetic route. This is a new and efficient strategy for the preparation of neoglycoconjugates. (author)

  4. Controlled delivery of Gemcitabine Hydrochloride using mannosylated poly(propyleneimine) dendrimers

    International Nuclear Information System (INIS)

    Soni, Namrata; Jain, Keerti; Gupta, Umesh; Jain, N. K.

    2015-01-01

    The aim of the present investigation was to deliver Gemcitabine Hydrochloride (GmcH), an anticancer bioactive, specifically to lung tumor cells using mannosylated 4.0G poly(propyleneimine) dendrimers (M-PPI). 4.0G poly(propyleneimine) (PPI) dendrimers was synthesized using ethylenediamine as core and conjugated with mannose by ring opening reactions, followed by Schiff’s reaction in the presence of sodium acetate buffer (pH 4.0). Synthesized PPI dendrimers and mannose-conjugated dendrimers were characterized using IR, NMR spectroscopy, and scanning electron microscopy. GmcH was loaded into PPI and M-PPI dendrimers using equilibrium dialysis method to develop the formulations, GmcH-PPI and GmcH-M-PPI, respectively. The developed formulations were evaluated for drug loading, in vitro release kinetics, in vitro stability, hemolytic toxicity, cytotoxicity, pharmacokinetic, and biodistribution studies. The dendrimeric formulation of GmcH showed pH-sensitive release with faster release at acidic pH, i.e., pH 4.0 in comparison with physiological pH 7.4. M-PPI conjugate showed significant reduction in hemolytic toxicity as compared to plain 4.0G PPI dendrimers towards human erythrocytes. In the cytotoxicity studies with A-549 lung adenocarcinoma cell line, the GmcH-M-PPI formulation showed the lowest IC 50 value. Further, the pharmacokinetic and tissue distribution studies of free drug GmcH, GmcH-PPI, and GmcH-M-PPI in albino rats of Sprague–Dawley strain suggested the mean residence time of GmcH-M-PPI conjugate to be significantly higher (24.85 h) than free GmcH and GmcH-PPI. Deposition of drug (396.1 ± 4.7 after 2 h) in lung was found to be significantly higher with GmcH-M-PPI formulation in comparison with Gmch and GmcH-PPI

  5. In vitro antibacterial activity of poly (amidoamine)-G7 dendrimer.

    Science.gov (United States)

    Gholami, Mitra; Mohammadi, Rashin; Arzanlou, Mohsen; Akbari Dourbash, Fakhraddin; Kouhsari, Ebrahim; Majidi, Gharib; Mohseni, Seyed Mohsen; Nazari, Shahram

    2017-06-05

    Nano-scale dendrimers are synthetic macromolecules that frequently used in medical and health field. Traditional anibiotics are induce bacterial resistence so there is an urgent need for novel antibacterial drug invention. In the present study seventh generation poly (amidoamine) (PAMAM-G7) dendrimer was synthesized and its antibacterial activities were evaluated against representative Gram- negative and Gram-positive bacteria. PAMAM-G7 was synthesized with divergent growth method. The structural and surface of PAMAM-G7 were investigated by transmission electron microscopy, scanning electron microscope and fourier transform infrared. Pseudomonas. aeruginosa (n = 15), E. coli (n = 15), Acinetobacter baumanni (n = 15), Shigella dysenteriae (n = 15), Klebsiella pneumoniae (n = 10), Proteus mirabilis (n = 15), Staphylococcus aureus (n = 15) and Bacillus subtilis (n = 10) have been used for antibacterial activity assay. Additionally, representative standard strains for each bacterium were included. Minimum Inhibitory Concentration (MIC) was determined using microdilution method. Subsequently, Minimum Bactericidal Concentration (MBC) was determined by sub-culturing each of the no growth wells onto Mueller Hinton agar medium. The cytotoxicity of PAMAM-G7 dendrimer were evaluated in HCT116 and NIH 3 T3 cells by MTT assay. The average size of each particle was approximately 20 nm. PAMAM-G7 was potentially to inhibit both Gram positive and gram negative growth. The MIC50 and MIC90 values were determined to be 2-4 μg/ml and 4-8 μg/ml, respectively. The MBC50 and MBC90 values were found to be 64-256 μg/ml and 128-256 μg/ml, respectively. The cytotoxity effect of dendrimer on HCT116 and NIH 3 T3 cells is dependent upon exposure time to and concentration of dendrimers. The most reduction (44.63 and 43%) in cell viability for HCT116 and NIH 3 T3 cells was observed at the highest concentration, 0.85 μM after 72 h treatmentm, respectively. This study

  6. Controlled delivery of Gemcitabine Hydrochloride using mannosylated poly(propyleneimine) dendrimers

    Energy Technology Data Exchange (ETDEWEB)

    Soni, Namrata; Jain, Keerti, E-mail: keertijain02@gmail.com; Gupta, Umesh, E-mail: umeshgupta175@gmail.com; Jain, N. K., E-mail: jnarendr@yahoo.co.in [Dr. H. S. Gour Central University, Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences (India)

    2015-11-15

    The aim of the present investigation was to deliver Gemcitabine Hydrochloride (GmcH), an anticancer bioactive, specifically to lung tumor cells using mannosylated 4.0G poly(propyleneimine) dendrimers (M-PPI). 4.0G poly(propyleneimine) (PPI) dendrimers was synthesized using ethylenediamine as core and conjugated with mannose by ring opening reactions, followed by Schiff’s reaction in the presence of sodium acetate buffer (pH 4.0). Synthesized PPI dendrimers and mannose-conjugated dendrimers were characterized using IR, NMR spectroscopy, and scanning electron microscopy. GmcH was loaded into PPI and M-PPI dendrimers using equilibrium dialysis method to develop the formulations, GmcH-PPI and GmcH-M-PPI, respectively. The developed formulations were evaluated for drug loading, in vitro release kinetics, in vitro stability, hemolytic toxicity, cytotoxicity, pharmacokinetic, and biodistribution studies. The dendrimeric formulation of GmcH showed pH-sensitive release with faster release at acidic pH, i.e., pH 4.0 in comparison with physiological pH 7.4. M-PPI conjugate showed significant reduction in hemolytic toxicity as compared to plain 4.0G PPI dendrimers towards human erythrocytes. In the cytotoxicity studies with A-549 lung adenocarcinoma cell line, the GmcH-M-PPI formulation showed the lowest IC{sub 50} value. Further, the pharmacokinetic and tissue distribution studies of free drug GmcH, GmcH-PPI, and GmcH-M-PPI in albino rats of Sprague–Dawley strain suggested the mean residence time of GmcH-M-PPI conjugate to be significantly higher (24.85 h) than free GmcH and GmcH-PPI. Deposition of drug (396.1 ± 4.7 after 2 h) in lung was found to be significantly higher with GmcH-M-PPI formulation in comparison with Gmch and GmcH-PPI.

  7. Enzymatic Synthesis of N-Acetyllactosamine (LacNAc Type 1 Oligomers and Characterization as Multivalent Galectin Ligands

    Directory of Open Access Journals (Sweden)

    Thomas Fischöder

    2017-08-01

    Full Text Available Repeats of the disaccharide unit N-acetyllactosamine (LacNAc occur as type 1 (Galβ1, 3GlcNAc and type 2 (Galβ1, 4GlcNAc glycosylation motifs on glycoproteins and glycolipids. The LacNAc motif acts as binding ligand for lectins and is involved in many biological recognition events. To the best of our knowledge, we present, for the first time, the synthesis of LacNAc type 1 oligomers using recombinant β1,3-galactosyltransferase from Escherichia coli and β1,3-N-acetylglucosaminyltranferase from Helicobacter pylori. Tetrasaccharide glycans presenting LacNAc type 1 repeats or LacNAc type 1 at the reducing or non-reducing end, respectively, were conjugated to bovine serum albumin as a protein scaffold by squarate linker chemistry. The resulting multivalent LacNAc type 1 presenting neo-glycoproteins were further studied for specific binding of the tumor-associated human galectin 3 (Gal-3 and its truncated counterpart Gal-3∆ in an enzyme-linked lectin assay (ELLA. We observed a significantly increased affinity of Gal-3∆ towards the multivalent neo-glycoprotein presenting LacNAc type 1 repeating units. This is the first evidence for differences in glycan selectivity of Gal-3∆ and Gal-3 and may be further utilized for tracing Gal-3∆ during tumor progression and therapy.

  8. Multivalent Peptidomimetic Conjugates as Inhibitors of Androgen Receptor Function in Therapy Resistant Prostate Cancer

    Science.gov (United States)

    2016-10-01

    Haugbro M, Imberg-Kazdan K, Logan SK, Kirshenbaum K, Garabedian MJ. Multivalent Peptoid Conjugates Which Overcome Enzalutamide Resistance in Prostate...attached documents Wang Y, Dehigaspitiya DC, Levine PM, Profit AA, Haugbro M, Imberg-Kazdan K, Logan SK, Kirshenbaum K, Garabedian MJ. Multivalent...Enzalutamide Resistance in Prostate Cancer Cells Yu Wang1, Dilani C. Dehigaspitiya2, Paul M. Levine2, Adam A. Profit3, Michael Haugbro2, Keren Imberg

  9. Multivalent Peptidomimetic Conjugates as Inhibitors of Androgen Receptor Function in Therapy-Resistant Prostate Cancer

    Science.gov (United States)

    2016-10-01

    K, Logan SK, Kirshenbaum K, Garabedian MJ. Multivalent Peptoid Conjugates Which Overcome Enzalutamide Resistance in Prostate Cancer Cells. Cancer...Wang Y, Dehigaspitiya DC, Levine PM, Profit AA, Haugbro M, Imberg-Kazdan K, Logan SK, Kirshenbaum K, Garabedian MJ. Multivalent Peptoid Conjugates...Prostate Cancer Cells Yu Wang1, Dilani C. Dehigaspitiya2, Paul M. Levine2, Adam A. Profit3, Michael Haugbro2, Keren Imberg-Kazdan4, Susan K. Logan1,5

  10. Molecularly precise dendrimer-drug conjugates with tunable drug release for cancer therapy.

    Science.gov (United States)

    Zhou, Zhuxian; Ma, Xinpeng; Murphy, Caitlin J; Jin, Erlei; Sun, Qihang; Shen, Youqing; Van Kirk, Edward A; Murdoch, William J

    2014-10-06

    The structural preciseness of dendrimers makes them perfect drug delivery carriers, particularly in the form of dendrimer-drug conjugates. Current dendrimer-drug conjugates are synthesized by anchoring drug and functional moieties onto the dendrimer peripheral surface. However, functional groups exhibiting the same reactivity make it impossible to precisely control the number and the position of the functional groups and drug molecules anchored to the dendrimer surface. This structural heterogeneity causes variable pharmacokinetics, preventing such conjugates to be translational. Furthermore, the highly hydrophobic drug molecules anchored on the dendrimer periphery can interact with blood components and alter the pharmacokinetic behavior. To address these problems, we herein report molecularly precise dendrimer-drug conjugates with drug moieties buried inside the dendrimers. Surprisingly, the drug release rates of these conjugates were tailorable by the dendrimer generation, surface chemistry, and acidity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Nanoscale effects in dendrimer-mediated targeting of neuroinflammation.

    Science.gov (United States)

    Nance, Elizabeth; Zhang, Fan; Mishra, Manoj K; Zhang, Zhi; Kambhampati, Siva P; Kannan, Rangaramanujam M; Kannan, Sujatha

    2016-09-01

    Neuroinflammation, mediated by activated microglia and astrocytes, plays a key role in the pathogenesis of many neurological disorders. Systemically-administered dendrimers target neuroinflammation and deliver drugs with significant efficacy, without the need for ligands. Elucidating the nanoscale aspects of targeting neuroinflammation will enable superior nanodevices for eventual translation. Using a rabbit model of cerebral palsy, we studied the in vivo contributions of dendrimer physicochemical properties and disease pathophysiology on dendrimer brain uptake, diffusion, and cell specific localization. Neutral dendrimers move efficiently within the brain parenchyma and rapidly localize in glial cells in regions of injury. Dendrimer uptake is also dependent on the extent of blood-brain-barrier breakdown, glial activation, and disease severity (mild, moderate, or severe), which can lend the dendrimer to be used as an imaging biomarker for disease phenotype. This new understanding of the in vivo mechanism of dendrimer-mediated delivery in a clinically-relevant rabbit model provides greater opportunity for clinical translation of targeted brain injury therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Transepithelial and endothelial transport of poly (amidoamine) dendrimers.

    Science.gov (United States)

    Kitchens, Kelly M; El-Sayed, Mohamed E H; Ghandehari, Hamidreza

    2005-12-14

    This article summarizes our efforts to evaluate the potential of poly (amidoamine) (PAMAM) dendrimers as carriers for oral drug delivery. Specifically, the permeability of a series of cationic PAMAM-NH2 (G0-G4) dendrimers across Caco-2 cell monolayers was evaluated as a function of dendrimer generation, concentration, and incubation time. The influence of dendrimer surface charge on the integrity, paracellular permeability, and viability of Caco-2 cell monolayers was monitored by measuring the transepithelial electrical resistance (TEER), 14C-mannitol permeability, and leakage of lactate dehydrogenase (LDH) enzyme, respectively. Microvascular extravasation of PAMAM-NH2 dendrimers in relation to their size, molecular weight, and molecular geometry is also discussed. Results of these studies show that transepithelial transport and microvascular extravasation of PAMAM dendrimers are dependent on their structural features including molecular size, molecular geometry, and surface chemistry. These results suggest that by optimizing the size and surface charge of PAMAM dendrimers, it is possible to develop oral delivery systems based on these carriers for targeted drug delivery.

  13. Dendrimer-Stabilized Ru Nanoparticles Immobilized in Organo-Silica Materials for Hydrogenation of Phenols

    Directory of Open Access Journals (Sweden)

    Eduard Karakhanov

    2017-03-01

    Full Text Available New hybrid catalysts based on Ru nanoparticles, encapsulated into poly(propylene imine dendrimers, immobilized into silica pores, were synthesized and examined for the hydrogenation of alkyl-substituted phenols. The corresponding alkyl-substituted cyclohexanols were presented as the major reaction products, while incomplete hydrogenation products appeared to be minor. A competition between the sterical factors of dendrimer-containing carriers and the electronic factors of substrate substituents influenced the hydrogenation rate of the alkyl-substituted phenols. The carrier structure was found to have a significant influence on both the physical and chemical properties of the catalysts and their hydrogenation activity. The synthesized hybrid catalysts appeared to be stable after recycling and could be re-used several times without significant loss of activity.

  14. Synergistic activity profile of carbosilane dendrimer G2-STE16 in combination with other dendrimers and antiretrovirals as topical anti-HIV-1 microbicide.

    Science.gov (United States)

    Sepúlveda-Crespo, Daniel; Lorente, Raquel; Leal, Manuel; Gómez, Rafael; De la Mata, Francisco J; Jiménez, José Luis; Muñoz-Fernández, M Ángeles

    2014-04-01

    Polyanionic carbosilane dendrimers represent opportunities to develop new anti-HIV microbicides. Dendrimers and antiretrovirals (ARVs) acting at different stages of HIV replication have been proposed as compounds to decrease new HIV infections. Thus, we determined the potential use of our G2-STE16 carbosilane dendrimer in combination with other carbosilane dendrimers and ARVs for the use as topical microbicide against HIV-1. We showed that these combinations obtained 100% inhibition and displayed a synergistic profile against different HIV-1 isolates in our model of TZM.bl cells. Our results also showed their potent activity in the presence of an acidic vaginal or seminal fluid environment and did not activate an inflammatory response. This study is the first step toward exploring the use of different anionic carbosilane dendrimers in combination and toward making a safe microbicide. Therefore, our results support further studies on dendrimer/dendrimer or dendrimer/ARV combinations as topical anti-HIV-1 microbicide. This paper describes the first steps toward the use of anionic carbosilane dendrimers in combination with antivirals to address HIV-1, paving the way to further studies on dendrimer/dendrimer or dendrimer/ARV combinations as topical anti-HIV-1 microbicides. © 2014.

  15. An intrinsically fluorescent dendrimer as a nanoprobe of cell transport.

    Science.gov (United States)

    Al-Jamal, Khuloud T; Ruenraroengsak, Pakatip; Hartell, Nicholas; Florence, Alexander T

    2006-07-01

    Dendrimers, spherical or quasi-spherical synthetic polymers in the nano-size range, have found useful applications as prospective carriers in drug and gene delivery. The investigation of dendrimer uptake by cells has been previously achieved by the incorporation of a fluorescent dye to the dendrimer either by chemical conjugation or by physical interaction. Here we describe the synthesis of two intrinsically fluorescent lysine based cationic dendrimers which lack a fluorophore, but which has sufficient fluorescence intensity to be detected at low concentrations. The nomenclature used to describe our compounds results in, for example the 6th generation dendrimer being notated as Gly-Lys(63) (NH2)(64); Gly denotes that the compound has a glycine in the core coupled to 63 lysine branching units (Lys(63)) and that the surface has 64 free amino groups (NH2)(64). The use of these dendrimers in probing transport avoids the need for fluorescent tagging with its attendant problems. The uptake of Gly-Lys(63) (NH2)(64) into Caco-2 cells was followed using confocal microscopy. Being cationic, it first adsorbs to the cell surface, enters the cytoplasm and reaches the nucleus within 35-45 min. Estimates of the diffusion coefficient of the dendrimer within the cell cytoplasm leads to a value of 6.27 ( +/- 0.49) x 10(-11) cm(2) s(-1), which is up to 1000 times lower than the diffusion coefficient of the dendrimer in water. Intrinsically fluorescent dendrimers of different size and charge are useful probes of transport in cells.

  16. Simulation of bulk phases formed by polyphilic liquid crystal dendrimers

    Directory of Open Access Journals (Sweden)

    J.M. Ilnytskyi

    2010-01-01

    Full Text Available A coarse-grained simulation model for a third generation liquid crystalline dendrimer (LCDr is presented. It allows, for the first time, for a successful molecular simulation study of a relation between the shape of a polyphilic macromolecular mesogen and the symmetry of a macroscopic phase. The model dendrimer consists of a soft central sphere and 32 grafted chains each terminated by a mesogen group. The mesogenic pair interactions are modelled by the recently proposed soft core spherocylinder model of Lintuvuori and Wilson [J. Chem. Phys, 128, 044906, (2008]. Coarse-grained (CG molecular dynamics (MD simulations are performed on a melt of 100 molecules in the anisotropic-isobaric ensemble. The model LCDr shows conformational bistability, with both rod-like and disc-like conformations stable at lower temperatures. Each conformation can be induced by an external aligning field of appropriate symmetry that acts on the mesogens (uniaxial for rod-like and planar for disc-like, leading to formation of a monodomain smectic A (SmA or a columnar (Col phase, respectively. Both phases are stable for approximately the same temperature range and both exhibit a sharp transition to an isotropic cubic-like phase upon heating. We observe a very strong coupling between the conformation of the LCDr and the symmetry of a bulk phase, as suggested previously by theory. The study reveals rich potential in terms of the application of this form of CG modelling to the study of molecular self-assembly of liquid crystalline macromolecules.

  17. Energy transfer to xanthene dyes in dansylated POPAM dendrimers

    Science.gov (United States)

    Aumanen, Jukka; Korppi-Tommola, Jouko

    2011-12-01

    Excitation energy transfer (EET) in host-guest complexes of dansylated POPAM dendrimers and xanthene dyes have been studied by transient absorption spectroscopy. EET from dansyl periphery to guests: rose bengal, eosin, or fluorescein, showed non-exponential behaviour as a result of distribution of donor-acceptor distances. Time constants range from 100 fs to 8 ps, independent of the dye and the dendrimer generation. Experiments suggested that in dendrimers binding more than one guest, EET among the guests becomes effective. Guest-host and guest-guest interactions induce non-radiative relaxation channels making excitation decays of the guests clearly faster in complexes than in solution.

  18. The effect of dendrimer on cotton dyeability with direct dyes

    Directory of Open Access Journals (Sweden)

    Khakzar Bafrooei F.

    2014-01-01

    Full Text Available Pretreatment of cotton fabric with poly(propylene imine dendrimer enhanced its colour strength using C.I. Direct Red 81 and C.I. Direct Blue 78. Application of this dendrimer and the direct dye simultaneously on cotton fabric by the exhaust and the continuous dyeing method were studied; slight improvements in the dyeing results were obtained. Pretreatment of the cotton fabric with dendrimer in an emulsion form using the pad-dry method followed by continuous dyeing markedly increased the colour strength. In addition, level dyeing was obtained, and no negative effects on the fastness properties of the dyes used were observed.

  19. Multivalent human papillomavirus l1 DNA vaccination utilizing electroporation.

    Directory of Open Access Journals (Sweden)

    Kihyuck Kwak

    Full Text Available Naked DNA vaccines can be manufactured simply and are stable at ambient temperature, but require improved delivery technologies to boost immunogenicity. Here we explore in vivo electroporation for multivalent codon-optimized human papillomavirus (HPV L1 and L2 DNA vaccination.Balb/c mice were vaccinated three times at two week intervals with a fusion protein comprising L2 residues ∼11-88 of 8 different HPV types (11-88×8 or its DNA expression vector, DNA constructs expressing L1 only or L1+L2 of a single HPV type, or as a mixture of several high-risk HPV types and administered utilizing electroporation, i.m. injection or gene gun. Serum was collected two weeks and 3 months after the last vaccination. Sera from immunized mice were tested for in-vitro neutralization titer, and protective efficacy upon passive transfer to naive mice and vaginal HPV challenge. Heterotypic interactions between L1 proteins of HPV6, HPV16 and HPV18 in 293TT cells were tested by co-precipitation using type-specific monoclonal antibodies.Electroporation with L2 multimer DNA did not elicit detectable antibody titer, whereas DNA expressing L1 or L1+L2 induced L1-specific, type-restricted neutralizing antibodies, with titers approaching those induced by Gardasil. Co-expression of L2 neither augmented L1-specific responses nor induced L2-specific antibodies. Delivery of HPV L1 DNA via in vivo electroporation produces a stronger antibody response compared to i.m. injection or i.d. ballistic delivery via gene gun. Reduced neutralizing antibody titers were observed for certain types when vaccinating with a mixture of L1 (or L1+L2 vectors of multiple HPV types, likely resulting from heterotypic L1 interactions observed in co-immunoprecipitation studies. High titers were restored by vaccinating with individual constructs at different sites, or partially recovered by co-expression of L2, such that durable protective antibody titers were achieved for each type.Multivalent

  20. Design of interior-functionalized fully acetylated dendrimers for anticancer drug delivery.

    Science.gov (United States)

    Hu, Jingjing; Su, Yunzhang; Zhang, Hongfeng; Xu, Tongwen; Cheng, Yiyun

    2011-12-01

    In this study, dendrimers was synthesized by introducing functional groups into the interior pockets of fully acetylated dendrimers. NMR techniques including COSY and 2D-NOESY revealed the molecular structures of the synthesized dendrimers and the encapsulation of guest molecule such as methotrexate within their interior pockets. The synthesized polymeric nanocarriers showed much lower cytotoxicity on two cell lines than cationic dendrimers, and exhibited better performance than fully acetylated dendrimers in the sustained release of methotrexate. The results provided a new strategy in the design of non-toxic dendrimers with high performance in the delivery of anti-cancer drugs for clinical applications. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Atomistic computer simulations on multi-loaded PAMAM dendrimers: a comparison of amine- and hydroxyl-terminated dendrimers

    Science.gov (United States)

    Badalkhani-Khamseh, Farideh; Ebrahim-Habibi, Azadeh; Hadipour, Nasser L.

    2017-12-01

    Poly(amidoamine) (PAMAM) dendrimers have been extensively studied as delivery vectors in biomedical applications. A limited number of molecular dynamics (MD) simulation studies have investigated the effect of surface chemistry on therapeutic molecules loading, with the aim of providing insights for biocompatibility improvement and increase in drug loading capacity of PAMAM dendrimers. In this work, fully atomistic MD simulations were employed to study the association of 5-Fluorouracil (5-FU) with amine (NH2)- and hydroxyl (OH)-terminated PAMAM dendrimers of generations 3 and 4 (G3 and G4). MD results show a 1:12, 1:1, 1:27, and 1:4 stoichiometry, respectively, for G3NH2-FU, G3OH-FU, G4NH2-FU, and G4OH-FU complexes, which is in good agreement with the isothermal titration calorimetry results. The results obtained showed that NH2-terminated dendrimers assume segmented open structures with large cavities and more drug molecules can encapsulate inside the dendritic cavities of amine terminated dendrimers. However, OH-terminated have a densely packed structure and therefore, 5-FU drug molecules are more stable to locate close to the surface of the dendrimers. Intermolecular hydrogen bonding analysis showed that 5-FU drug molecules have more tendency to form hydrogen bonds with terminal monomers of OH-terminated dendrimers, while in NH2-terminated these occur both in the inner region and the surface. Furthermore, MM-PBSA analysis revealed that van der Waals and electrostatic energies are both important to stabilize the complexes. We found that drug molecules are distributed uniformly inside the amine and hydroxyl terminated dendrimers and therefore, both dendrimers are promising candidates as drug delivery systems for 5-FU drug molecules.

  2. Dual stimuli-sensitive dendrimers: Photothermogenic gold nanoparticle-loaded thermo-responsive elastin-mimetic dendrimers.

    Science.gov (United States)

    Fukushima, Daichi; Sk, Ugir Hossain; Sakamoto, Yasuhiro; Nakase, Ikuhiko; Kojima, Chie

    2015-08-01

    Dendrimers are synthetic macromolecules with unique structures that can work as nanoplatforms for both photothermogenic gold nanoparticles (AuNPs) and thermosensitive elastin-like peptides (ELPs) with valine-proline-glycine-valine-glycine (VPGVG) repeats. In this study, photothermogenic AuNPs were loaded into thermo-responsive elastin-mimetic dendrimers (dendrimers conjugating ELPs at their periphery) to produce dual stimuli-sensitive nanoparticles. Polyamidoamine G4 dendrimers were modified with acetylated VPGVG and (VPGVG)2, and the resulting materials were named ELP1-den and ELP2-den, respectively. The AuNPs were prepared by the reduction of Au ions using a dendrimer-nanotemplated method. The AuNP-loaded elastin-mimetic dendrimers exhibited photothermal properties. ELP1-den and ELP2-den showed similar temperature-dependent changes in their conformations. Phase transitions were observed at around 55°C and 35°C for the AuNP-loaded ELP1-den and AuNP-loaded ELP2-den, respectively, but not for the corresponding PEGylated dendrimer. In contrast to the AuNP-loaded PEGylated dendrimer, AuNP-loaded ELP2-den readily associated with cells and induced efficient photocytotoxicity at 37°C. The cell association and the photocytotoxicity properties of AuNP-loaded ELP2-den could be controlled by temperature. These results therefore suggest that dual stimuli-sensitive dendrimer nanoparticles of this type could be used for photothermal therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. A star-shaped polythiophene dendrimer coating for solid-phase microextraction of triazole agrochemicals.

    Science.gov (United States)

    Abolghasemi, Mir Mahdi; Habibiyan, Rahim; Jaymand, Mehdi; Piryaei, Marzieh

    2018-02-14

    A nanostructured star-shaped polythiophene dendrimer was prepared and used as a fiber coating for headspace solid phase microextraction of selected triazolic pesticides (tebuconazole, hexaconazole, penconazole, diniconazole, difenoconazole, triticonazole) from water samples. The dendrimer with its large surface area was characterized by thermogravimetric analysis, UV-Vis spectroscopy and field emission scanning electron microscopy. It was placed on a stainless steel wire for use in SPME. The experimental conditions for fiber coating, extraction, stirring rate, ionic strength, pH value, desorption temperature and time were optimized. Following thermal desorption, the pesticides were quantified by GC-MS. Under optimum conditions, the repeatability (RSD) for one fiber (for n = 3) ranges from 4.3 to 5.6%. The detection limits are between 8 and 12 pg mL -1 . The method is fast, inexpensive (in terms of equipment), and the fiber has high thermal stability. Graphical abstract Schematic presentation of a nanostructured star-shaped polythiophene dendrimer for use in headspace solid phase microextraction of the triazolic pesticides (tebuconazole, hexaconazole, penconazole, diniconazole, difenoconazole, triticonazole). They were then quantified by gas chromatography-mass spectrometry.

  4. Delivery systems for biopharmaceuticals. Part II: Liposomes, Micelles, Microemulsions and Dendrimers.

    Science.gov (United States)

    Silva, Ana C; Lopes, Carla M; Lobo, José M S; Amaral, Maria H

    2015-01-01

    Biopharmaceuticals are a generation of drugs that include peptides, proteins, nucleic acids and cell products. According to their particular molecular characteristics (e.g. high molecular size, susceptibility to enzymatic activity), these products present some limitations for administration and usually parenteral routes are the only option. To avoid these limitations, different colloidal carriers (e.g. liposomes, micelles, microemulsions and dendrimers) have been proposed to improve biopharmaceuticals delivery. Liposomes are promising drug delivery systems, despite some limitations have been reported (e.g. in vivo failure, poor long-term stability and low transfection efficiency), and only a limited number of formulations have reached the market. Micelles and microemulsions require more studies to exclude some of the observed drawbacks and guarantee their potential for use in clinic. According to their peculiar structures, dendrimers have been showing good results for nucleic acids delivery and a great development of these systems during next years is expected. This is the Part II of two review articles, which provides the state of the art of biopharmaceuticals delivery systems. Part II deals with liposomes, micelles, microemulsions and dendrimers.

  5. Potent inhibition of tau fibrillization with a multivalent ligand

    International Nuclear Information System (INIS)

    Honson, Nicolette S.; Jensen, Jordan R.; Darby, Michael V.; Kuret, Jeff

    2007-01-01

    Small-molecule inhibitors of tau fibrillization are under investigation as tools for interrogating the tau aggregation pathway and as potential therapeutic agents for Alzheimer's disease. Established inhibitors include thiacarbocyanine dyes, which can inhibit recombinant tau fibrillization in the presence of anionic surfactant aggregation inducers. In an effort to increase inhibitory potency, a cyclic bis-thiacarbocyanine molecule containing two thiacarbocyanine moieties was synthesized and characterized with respect to tau fibrillization inhibitory activity by electron microscopy and ligand aggregation state by absorbance spectroscopy. Results showed that the inhibitory activity of the bis-thiacarbocyanine was qualitatively similar to a monomeric cyanine dye, but was more potent with 50% inhibition achieved at ∼80 nM concentration. At all concentrations tested in aqueous solution, the bis-thiacarbocyanine collapsed to form a closed clamshell structure. However, the presence of tau protein selectively stabilized the open conformation. These results suggest that the inhibitory activity of bis-thiacarbocyanine results from multivalency, and reveal a route to more potent tau aggregation inhibitors

  6. Enhancement of superconducting transition temperature in FeSe electric-double-layer transistor with multivalent ionic liquids

    Science.gov (United States)

    Miyakawa, Tomoki; Shiogai, Junichi; Shimizu, Sunao; Matsumoto, Michio; Ito, Yukihiro; Harada, Takayuki; Fujiwara, Kohei; Nojima, Tsutomu; Itoh, Yoshimitsu; Aida, Takuzo; Iwasa, Yoshihiro; Tsukazaki, Atsushi

    2018-03-01

    We report on an enhancement of the superconducting transition temperature (Tc) of the FeSe-based electric-double-layer transistor (FeSe-EDLT) by applying the multivalent oligomeric ionic liquids (ILs). The IL composed of dimeric cation (divalent IL) enables a large amount of charge accumulation on the surface of the FeSe ultrathin film, resulting in inducing electron-rich conduction even in a rather thick 10 nm FeSe channel. The onset Tc in FeSe-EDLT with the divalent IL is enhanced to be approaching about 50 K at the thin limit, which is about 7 K higher than that in EDLT with conventional monovalent ILs. The enhancement of Tc is a pronounced effect of the application of the divalent IL, in addition to the large capacitance, supposing preferable interface formation of ILs driven by geometric and/or Coulombic effect. The present finding strongly indicates that multivalent ILs are powerful tools for controlling and improving physical properties of materials.

  7. From dendrimers to fractal polymers and beyond

    Directory of Open Access Journals (Sweden)

    Charles N. Moorefield

    2013-01-01

    Full Text Available The advent of dendritic chemistry has facilitated materials research by allowing precise control of functional component placement in macromolecular architecture. The iterative synthetic protocols used for dendrimer construction were developed based on the desire to craft highly branched, high molecular weight, molecules with exact mass and tailored functionality. Arborols, inspired by trees and precursors of the utilitarian macromolecules known as dendrimers today, were the first examples to employ predesigned, 1 → 3 C-branched, building blocks; physical characteristics of the arborols, including their globular shapes, excellent solubilities, and demonstrated aggregation, combined to reveal the inherent supramolecular potential (e.g., the unimolecular micelle of these unique species. The architecture that is a characteristic of dendritic materials also exhibits fractal qualities based on self-similar, repetitive, branched frameworks. Thus, the fractal design and supramolecular aspects of these constructs are suggestive of a larger field of fractal materials that incorporates repeating geometries and are derived by complementary building block recognition and assembly. Use of terpyridine-M2+-terpyridine (where, M = Ru, Zn, Fe, etc connectivity in concert with mathematical algorithms, such as forms the basis for the Seirpinski gasket, has allowed the beginning exploration of fractal materials construction. The propensity of the fractal molecules to self-assemble into higher order architectures adds another dimension to this new arena of materials and composite construction.

  8. Engineering of dendrimer surfaces to enhance transepithelial transport and reduce cytotoxicity.

    Science.gov (United States)

    Jevprasesphant, Rachaneekorn; Penny, Jeffrey; Attwood, David; McKeown, Neil B; D'Emanuele, Antony

    2003-10-01

    To evaluate the cytotoxicity, permeation, and transport mechanisms of PAMAM dendrimers and surface-modified cationic PAMAM dendrimers using monolayers of the human colon adenocarcinoma cell line, Caco-2. Cytotoxicity was determined using the MTT assay. The effect of dendrimers on monolayer integrity was determined from measurements of transepithelial electrical resistance (TEER) and [14C]mannitol apparent permeability coefficient (Papp). The Papp of dendrimers through monolayers was measured in both the apical (A)-to-basolateral (B) and B --> A directions at 4 degrees C and 37 degrees C and also in the presence and absence of ethylenediamine tetraacetic acid (EDTA) and colchicine. The cytotoxicity and permeation of dendrimers increased with both concentration and generation. The cytotoxicity of cationic dendrimers (G2, G3, G4) was greater than that of anionic dendrimers (G2.5, G3.5) but was reduced by conjugation with lauroyl chloride: the least cytotoxic conjugates were those with six attached lauroyl chains. At 37 degrees C the Papp of cationic dendrimers was higher than that of anionic dendrimers and, in general, increased with the number of attached lipid chains. Cationic dendrimers decreased TEER and significantly increased the Papp of mannitol. Modified dendrimers also reduced TEER and caused a more marked increase in the Papp of mannitol. The Papp values of dendrimers and modified dendrimers were higher in the presence of EDTA, lower in the presence of colchicine, and lower at 4 degrees C than at 37 degrees C. The properties of dendrimers may be significantly modified by surface engineering. Conjugation of cationic PAMAM dendrimers with lauroyl chloride decreased their cytotoxicity and increased their permeation through Caco-2 cell monolayers. Both PAMAM dendrimers and lauroyl-PAMAM dendrimer conjugates can cross epithelial monolayers by paracellular and transcellular pathways.

  9. Smart dendrimer-based nanogel for enhancing 5-fluorouracil ...

    Indian Academy of Sciences (India)

    Author for correspondence (nckhoavnn@yahoo.com) chemical properties of the ..... accounting for 90% of loaded 5-FU from dialysis membrane, whereas ... of the NIPAM layer-coated dendrimer contributed to control the drug sustainably from ...

  10. Preparation and evaluation of peptide-dendrimer-paclitaxel ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research April 2017; 16 (4): 737-742 ... conjugates for treatment of heterogeneous stage 1 non- small cell lung ... Keywords: Paclitaxel, Lung cancer, Non-small cell lung cancer, Dendrimer, Peptide, PAMAM.

  11. Formulation and Development of Dendrimer-Based Transdermal ...

    African Journals Online (AJOL)

    Shandong Traditional Chinese Medicine University, Jinan 250012, China ... system for the management of some diseased conditions. Keywords: Dendrimers ... anti-inflammatory and analgesic activity [3]. ..... Cost-effective management of.

  12. Dendrimer Advances for the Central Nervous System Delivery of Therapeutics

    Science.gov (United States)

    2013-01-01

    The effectiveness of noninvasive treatment for central nervous system (CNS) diseases is generally limited by the poor access of therapeutic agents into the CNS. Most CNS drugs cannot permeate into the brain parenchyma because of the blood-brain barrier (BBB), and overcoming this has become one of the most significant challenges in the development of CNS therapeutics. Rapid advances in nanotechnology have provided promising solutions to this challenge. This review discusses the latest applications of dendrimers in the treatment of CNS diseases with an emphasis on brain tumors. Dendrimer-mediated drug delivery, imaging, and diagnosis are also reviewed. The toxicity, biodistribution, and transport mechanisms in dendrimer-mediated delivery of CNS therapeutic agents bypassing or crossing the BBB are also discussed. Future directions and major challenges of dendrimer-mediated delivery of CNS therapeutic agents are included. PMID:24274162

  13. Thermodynamic properties of a liquid crystal carbosilane dendrimer

    Science.gov (United States)

    Samosudova, Ya. S.; Markin, A. V.; Smirnova, N. N.; Ogurtsov, T. G.; Boiko, N. I.; Shibaev, V. P.

    2016-11-01

    The temperature dependence of the heat capacity of a first-generation liquid crystal carbosilane dendrimer with methoxyphenyl benzoate end groups is studied for the first time in the region of 6-370 K by means of precision adiabatic vacuum calorimetry. Physical transformations are observed in this interval of temperatures, and their standard thermodynamic characteristics are determined and discussed. Standard thermodynamic functions C p ° ( T), H°( T) - H°(0), S°( T) - S°(0), and G°( T) - H°(0) are calculated from the obtained experimental data for the region of T → 0 to 370 K. The standard entropy of formation of the dendrimer in the partially crystalline state at T = 298.15 K is calculated, and the standard entropy of the hypothetic reaction of its synthesis at this temperature is estimated. The thermodynamic properties of the studied dendrimer are compared to those of second- and fourth-generation liquid crystal carbosilane dendrimers with the same end groups studied earlier.

  14. Dendrimer advances for the central nervous system delivery of therapeutics.

    Science.gov (United States)

    Xu, Leyuan; Zhang, Hao; Wu, Yue

    2014-01-15

    The effectiveness of noninvasive treatment for central nervous system (CNS) diseases is generally limited by the poor access of therapeutic agents into the CNS. Most CNS drugs cannot permeate into the brain parenchyma because of the blood-brain barrier (BBB), and overcoming this has become one of the most significant challenges in the development of CNS therapeutics. Rapid advances in nanotechnology have provided promising solutions to this challenge. This review discusses the latest applications of dendrimers in the treatment of CNS diseases with an emphasis on brain tumors. Dendrimer-mediated drug delivery, imaging, and diagnosis are also reviewed. The toxicity, biodistribution, and transport mechanisms in dendrimer-mediated delivery of CNS therapeutic agents bypassing or crossing the BBB are also discussed. Future directions and major challenges of dendrimer-mediated delivery of CNS therapeutic agents are included.

  15. Synthesis of Dendrimer Containing Carbazole Unit as a Core Chromophore

    International Nuclear Information System (INIS)

    Han, Seung Choul; Lee, Jae Wook; Jin, Sungho

    2012-01-01

    Dendrimers, which are prepared by repetition of a given set of reactions using either divergent or convergent strategies, are highly branched and regular macromolecules with well-defined structures and have served as functional objects in nanotechnology and nano-materials science. Following conventional organic small molecules and polymers, dendrimers are now regarded as the third class of materials for use in organic light-emitting diodes (OLEDs) and have attracted much attention due to their distinguished properties. Dendrimers contain three distinct structural parts that are the core, end-groups, and branched units connecting core and periphery. For light-emitting dendrimers, the core is usually selected as the luminescent chromophore, and the dendrons and their periphery are charge transporting units and can also tune the solubility. In contrast to linear polymers, dendrimers are sphere-like with dimensions of the order of nanometers depending on the generation number. By careful structural design, dendrimers combine the potential advantages of both small molecules and polymers. Therefore, the innovative strategy different from conventional convergent and divergent routes has been required to simplify dendrimer synthesis. Recent solid chemistry is the click chemistry which is the copper-catalyzed 1,3-dipolar cycloaddition reaction between alkyne and azide developed by Sharpless and Tornφe. This reaction has many advantages: very high yields, mild and simple reaction conditions, oxygen and water tolerance, and easy isolation of product. This reaction is clearly a breakthrough in the synthesis of dendrimers and dendritic and polymer materials. We have developed the fusion and stitching methods for the synthesis of various dendrimers using click chemistry between an alkyne and an azide. Overall, this method was found to be a straightforward strategy for the synthesis of triazole-based dendrimers. Taking advantage of this fact, herein we report a feasible route

  16. Biological properties of water-soluble phosphorhydrazone dendrimers

    Directory of Open Access Journals (Sweden)

    Anne-Marie Caminade

    2013-01-01

    Full Text Available Dendrimers are hyperbranched and perfectly defined macromolecules, constituted of branches emanating from a central core in an iterative fashion. Phosphorhydrazone dendrimers constitute a special family of dendrimers, possessing one phosphorus atom at each branching point. The internal structure of these dendrimers is hydrophobic, but hydrophilic terminal groups can induce the solubility of the whole structure in water. Indeed, the properties of these compounds are mainly driven by the type of terminal groups their bear; this is especially true for the biological properties. For instance, positively charged terminal groups are efficient for transfection experiments, as drug carriers, as anti-prion agents, and as inhibitor of the aggregation of Alzheimer's peptides, whereas negatively charged dendrimers have anti-HIV properties and can influence the human immune system, leading to anti-inflammatory properties usable against rheumatoid arthritis. This review will give the most representative examples of the biological properties of water-soluble phosphorhydrazone dendrimers, organized depending on the type of terminal groups they bear.

  17. Biphasic interactions between a cationic dendrimer and actin.

    Science.gov (United States)

    Ruenraroengsak, Pakatip; Florence, Alexander T

    2010-12-01

    Gene delivery systems face the problem not only of the route toward the cell and tissues in question, but also of the molecularly crowded environment of both the cytoplasm and the nucleus itself. One of the physical barriers in the cytoplasm for diffusing nanoparticles is an actin network. Here, we describe the finding that a self-fluorescent sixth generation cationic dendrimer (6 nm in diameter) interacts reversibly and possibly electrostatically with actin filaments in vitro. Not only does this interaction slow the diffusion of the dendrimer but it also affects actin polymerization in a biphasic manner. At low concentrations the dendrimer behaves like a G-binding actin protein, retarding actin polymerization, whereas at high concentrations the dendrimer acts as a nucleating protein accelerating the polymerization. Thus in vivo the diffusion of a dendrimer carrier such as this has both physical and chemical elements: by decreasing polymerization it might accelerate its own transport, and by enhancing actin polymerization retard it. This finding suggests that such a dendrimer may have a role as an anticancer agent through its inhibitory effect on actin polymerization.

  18. In vitro evaluation of dendrimer prodrugs for oral drug delivery.

    Science.gov (United States)

    Najlah, Mohammad; Freeman, Sally; Attwood, David; D'Emanuele, Antony

    2007-05-04

    Dendrimer-based prodrugs were used to enhance the transepithelial permeability of naproxen, a low solubility model drug. The stability of the dendrimer-naproxen link was assessed. Naproxen was conjugated to G0 polyamidoamine (PAMAM) dendrimers either by an amide bond or an ester bond. The stability of G0 prodrugs was evaluated in 80% human plasma and 50% rat liver homogenate. The cytotoxicity of conjugates towards Caco-2 cells was determined and the transport of the conjugates across Caco-2 monolayers (37 degrees C) was reported. In addition, one lauroyl chain (L) was attached to the surface group of G0 PAMAM dendrimer of the diethylene glycol ester conjugate (G0-deg-NAP) to enhance permeability. The lactic ester conjugate, G0-lact-NAP, hydrolyzed slowly in 80% human plasma and in 50% rat liver homogenate (t(1/2)=180 min). G0-deg-NAP was hydrolyzed more rapidly in 80% human plasma (t(1/2)=51 min) and was rapidly cleaved in 50% liver homogenate (t(1/2)=4.7 min). The conjugates were non-toxic when exposed to Caco-2 cells for 3h. Permeability studies showed a significant enhancement in the transport of naproxen when conjugated to dendrimers; L-G0-deg-NAP yielding the highest permeability. Dendrimer-based prodrugs with appropriate linkers have potential as carriers for the oral delivery of low solubility drugs such as naproxen.

  19. Exciton Transport Simulations in Phenyl Cored Thiophene Dendrimers

    Science.gov (United States)

    Kim, Kwiseon; Erkan Kose, Muhammet; Graf, Peter; Kopidakis, Nikos; Rumbles, Garry; Shaheen, Sean E.

    2009-03-01

    Phenyl cored 3-arm and 4-arm thiophene dendrimers are promising materials for use in photovoltaic devices. It is important to understand the energy transfer mechanisms in these molecules to guide the synthesis of novel dendrimers with improved efficiency. A method is developed to estimate the exciton diffusion lengths for the dendrimers and similar chromophores in amorphous films. The approach exploits Fermi's Golden Rule to estimate the energy transfer rates for an ensemble of bimolecular complexes in random orientations. Using Poisson's equation to evaluate Coulomb integrals led to efficient calculation of excitonic couplings between the transition densities. Monte-Carlo simulations revealed the dynamics of energy transport in the dendrimers. Experimental exciton diffusion lengths of the dendrimers range 10 ˜ 20 nm, increasing with the size of the dendrimer. Simulated diffusion lengths correlate well with experiments. The chemical structure of the chromophore, the shape of the transition densities and the exciton lifetime are found to be the most important factors that determine the exciton diffusion length in amorphous films.

  20. Gene Transfer in Eukaryotic Cells Using Activated Dendrimers

    Science.gov (United States)

    Dennig, Jörg

    Gene transfer into eukaryotic cells plays an important role in cell biology. Over the last 30 years a number of transfection methods have been developed to mediate gene transfer into eukaryotic cells. Classical methods include co-precipitation of DNA with calcium phosphate, charge-dependent precipitation of DNA with DEAE-dextran, electroporation of nucleic acids, and formation of transfection complexes between DNA and cationic liposomes. Gene transfer technologies based on activated PAMAM-dendrimers provide another class of transfection reagents. PAMAM-dendrimers are highly branched, spherical molecules. Activation of newly synthesized dendrimers involves hydrolytic removal of some of the branches, and results in a molecule with a higher degree of flexibility. Activated dendrimers assemble DNA into compact structures via charge interactions. Activated dendrimer - DNA complexes bind to the cell membrane of eukaryotic cells, and are transported into the cell by non-specific endocytosis. A structural model of the activated dendrimer - DNA complex and a potential mechanism for its uptake into cells will be discussed.

  1. Osseointegration of implants with dendrimers surface characteristics installed conventionally or with Piezosurgery®. A comparative study in the dog.

    Science.gov (United States)

    Bengazi, Franco; Lang, Niklaus P; Canciani, Elena; Viganò, Paolo; Velez, Joaquin Urbizo; Botticelli, Daniele

    2014-01-01

    The first aim of the present experiment was to compare bone healing at implants installed in recipient sites prepared with conventional drills or a piezoelectric device. The second aim was to compare implant osseointegration onto surfaces with and without dendrimers coatings. Six Beagles dogs were used in this study. Five implants with two different surfaces, three with a ZirTi(®) surface (zirconia sand blasted, acid etched), and two with a ZirTi(®)-modified surface with dendrimers of phosphoserine and polylysine were installed in the right side of the mandible. In the most anterior region (P2, P3), two recipient sites were prepared with drills, and one implant ZirTi(®) surface and one coated with dendrimers implants were installed at random. In the posterior region (P4 and M1), three recipient sites were randomly prepared: two sites with a Piezosurgery(®) instrument and one site with drill and two ZirTi(®) surface and one coated with dendrimers implants installed. Three months after the surgery, the animals were sacrificed for histological analysis. No complications occurred during the healing period. Three implants were found not integrated and were excluded from analysis. However, n = 6 was obtained. The distance IS-B at the buccal aspect was 2.2 ± 0.8 and 1.8 ± 0.5 mm, while IS-C was 1.5 ± 0.9 and 1.4 ± 0.6 mm at the Piezosurgery(®) and drill groups, respectively. Similar values were obtained between the dendrimers-coated and ZirTi(®) surface implants. The BIC% values were higher at the drill (72%) compared to the Piezosurgery(®) (67%) sites. The BIC% were also found to be higher at the ZirTi(®) (74%) compared to the dendrimers-coated (65%) implants, the difference being statistically significant. This study has revealed that oral implants may osseointegrate equally well irrespective of whether their bed was prepared utilizing conventional drills with abundant cooling or Piezosurgery(®). Moreover, the surface coating of implants with dendrimers

  2. Ultrafast Dynamics of Dansylated POPAM Dendrimers and Energy Transfer in their Dye Complexes

    Science.gov (United States)

    Aumanen, J.; Kesti, T.; Sundström, V.; Vögtle, F.; Korppi-Tommola, J.

    We have studied internal dynamics of dansylated poly(propyleneamine) dendrimers of different generations in solution and excitation energy transfer from dansyl chromophores to xanthene dyes that form van der Waals complexes with the dendrimers

  3. DNA compaction by poly (amido amine) dendrimers of ammonia cored and ethylene diamine cored

    Science.gov (United States)

    Qamhieh, K.; Al-Shawwa, J.

    2017-06-01

    The complexes build-up of DNA and soft particles poly amidoamine (PAMAM) dendrimers of ammonia cored of generations (G1-G6) and ethylenediamine cored of generations (G1-G10) have been studied, using a new theoretical model developed by Qamhieh and coworkers. The model describes the interaction between linear polyelectrolyte (LPE) chain and ion-penetrable spheres. Many factors affecting LPE/dendrimer complex have been investigated such as dendrimer generation, the Bjerrum length, salt concentration, and rigidity of the LPE chain represented by the persistence length. It is found that the wrapping chain length around dendrimer increases by increasing dendrimer`s generation, Bjerrum length, and salt concentration, while decreases by increasing the persistence length of the LPE chain. Also we can conclude that the wrapping length of LPE chain around ethylenediamine cored dendrimers is larger than its length around ammonia cored dendrimers.

  4. Molecular boxes on a molecular printboard: encapsulation of anionic dyes in immobilized dendrimers

    NARCIS (Netherlands)

    Onclin, S.; Huskens, Jurriaan; Ravoo, B.J.; Reinhoudt, David

    2005-01-01

    Fifth-generation poly(propylene imine) dendrimers, modified with 64 apolar adamantyl groups, have been immobilized on cyclodextrin host monolayers (molecular printboards) on glass by supramolecular microcontact printing. The immobilized dendrimers retain their guest-binding properties and function

  5. Design and syntheses of mono and multivalent mannosyl-lipoconjugates for targeted liposomal drug delivery.

    Science.gov (United States)

    Štimac, Adela; Cvitaš, Jelena TrmĿiĿ; Frkanec, Leo; Vugrek, Oliver; Frkanec, Ruža

    2016-09-10

    Multivalent mannosyl-lipoconjugates may be of interest for glycosylation of liposomes and targeted drug delivery because the mannose specifically binds to C-type lectin receptors on the particular cells. In this paper syntheses of two types of novel O-mannosides are presented. Conjugates 1 and 2 with a COOH- and NH2-functionalized spacer and the connection to a lysine and FmocNH-PEG-COOH, are described. The coupling reactions of prepared intermediates 6 and 4 with a PEGylated-DSPE or palmitic acid, respectively, are presented. Compounds 5, mono-, 8, di- and 12, tetravalent mannosyl-lipoconjugates, were synthesized. The synthesized compounds were incorporated into liposomes and liposomal preparations featuring exposed mannose units were characterized. Carbohydrate liposomal quartz crystal microbalance based assay has been established for studying carbohydrate-lectin binding. It was demonstrated that liposomes with incorporated mannosyl-lipoconjugates were effectively recognized by Con A and have great potential to be used for targeted liposomal drug delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Electrical switching and memory phenomena observed in redox-gradient dendrimer sandwich devices

    OpenAIRE

    Li, JianChang; Blackstock, Silas C.; Szulczewski, Greg J.

    2005-01-01

    We report on the fabrication of dendrimer sandwich devices with electrical switching and memory properties. The storage media is consisted of a redox-gradient dendrimer layer sandwiched in organic barrier thin films. The dendrimer layer acts as potential well where redox-state changes and consequent electrical transitions of the embedded dendrimer molecules are expected to be effectively triggered and retained, respectively. Experimental results indicated that electrical switching could be re...

  7. Understanding specific and nonspecific toxicities: a requirement for the development of dendrimer-based pharmaceuticals

    OpenAIRE

    McNerny, Daniel Q.; Leroueil, Pascale R.; Baker, James R.

    2010-01-01

    Dendrimer conjugates for pharmaceutical development are capable of enhancing the local delivery of cytotoxic drugs. The ability to conjugate different targeting ligands to the dendrimer allows for the cytotoxic drug to be focused at the intended target cell while minimizing collateral damage in normal cells. Dendrimers offer several advantages over other polymer conjugates by creating a better defined, more monodisperse therapeutic scaffold. Toxicity from the dendrimer, targeted and nonspecif...

  8. Permeability of surface modified polyamidoamine (PAMAM) dendrimers across Caco-2 cell monolayers

    OpenAIRE

    Yellepeddi, Venkata K.; Pisal, Dipak S.; Kumar, Ajay; Kaushik, Radhey S.; Hildreth, Michael B.; Guan, Xiangming; Palakurthi, Srinath

    2007-01-01

    Aim of this study was to prepare polyamine-conjugated PAMAM dendrimers and study their permeability across Caco-2 cell monolayers. Polyamines, namely, arginine and ornithine were conjugated to the amine terminals of the G4 PAMAM dendrimers by Fmoc synthesis. The apical-to-basolateral (AB) and basolateral-to-apical (BA) apparent permeability coefficients (Papp) for the PAMAM dendrimers increased by conjugating the dendrimers with both of the polyamines. The enhancement in permeability was depe...

  9. Synthesis and optical properties of water-soluble biperylene-based dendrimers.

    Science.gov (United States)

    Shao, Pin; Jia, Ningyang; Zhang, Shaojuan; Bai, Mingfeng

    2014-05-30

    We report the synthesis and photophysical properties of three biperylene-based dendrimers, which show red fluorescence in water. A fluorescence microscopy study demonstrated uptake of biperylene-based dendrimers in living cells. Our results indicate that these biperylene-based dendrimers are promising candidates in fluorescence imaging applications with the potential as therapeutic carriers.

  10. A selective glucose sensor: the cooperative effect of monoboronic acid-modified poly(amidoamine) dendrimers.

    Science.gov (United States)

    Tsai, Ching-Hua; Tang, Yi-Hsuan; Chen, Hui-Ting; Yao, Yi-Wen; Chien, Tun-Cheng; Kao, Chai-Lin

    2018-05-01

    Selective glucose binding was identified through five generations of monoboronic acid-functionalized PAMAM dendrimers. The best selectivity obtained when using G3 dendrimers (1b) generated 71.1, 94.9, and 1309 times stronger binding than when using galactose, fructose, and lactose, respectively. Further experiments using dendrimer analogues and glucose derivatives suggested that two nearby monoboronic acids cooperatively bound one glucose.

  11. The effect of dendrimer charge inversion in complexes with linear polyelectrolytes

    NARCIS (Netherlands)

    Lyulin, S.V.; Lyulin, A.V.; Darinskii, A.A.; Emri, I.

    2005-01-01

    The structure of complexes formed by charged dendrimers and oppositely charged linear chains with a charge of at least the same as that of dendrimers was studied by computer simulation using the Brownian dynamics method. The freely jointed, free-draining model of the dendrimer and the linear chain

  12. Investigation of interactions between dendrimer-coated magnetite nanoparticles and bovine serum albumin

    International Nuclear Information System (INIS)

    Pan Bifeng; Gao Feng; Ao Limei

    2005-01-01

    We investigated the interactions between dendrimer-coated magnetite nanoparticles (MNPs) and the protein serum albumin. The investigation was based on the fluorescence quenching of tryptophan residue of serum albumin after binding with the dendrimer-coated magnetite nanoparticles. The extent of the interactions between bovine serum albumin and dendrimer-coated MNPs strongly depends on their surface groups and pH value

  13. Build-up enhancement of photoluminescence from phenylazomethine bismuth dendrimer using Bi(OTf)3

    Science.gov (United States)

    Kambe, Tetsuya; Imaoka, Shotaro; Imaoka, Takane; Yamamoto, Kimihisa

    2018-05-01

    Metal assembly to a dendrimer can provide various functionalities based on the branched structure. Here, we researched assembly phenomena of bismuth salts in the phenylazomethine dendrimer and achieved enhancement of emission intensity per metal unit by using Bi(OTf)3. This enhancement suggested increasing of Bi-N coordination bonds derived from the bismuth units in the dendrimer.

  14. Interactions of poly(amidoamine) dendrimers with human serum albumin: binding constants and mechanisms.

    Science.gov (United States)

    Giri, Jyotsnendu; Diallo, Mamadou S; Simpson, André J; Liu, Yi; Goddard, William A; Kumar, Rajeev; Woods, Gwen C

    2011-05-24

    The interactions of nanomaterials with plasma proteins have a significant impact on their in vivo transport and fate in biological fluids. This article discusses the binding of human serum albumin (HSA) to poly(amidoamine) [PAMAM] dendrimers. We use protein-coated silica particles to measure the HSA binding constants (K(b)) of a homologous series of 19 PAMAM dendrimers in aqueous solutions at physiological pH (7.4) as a function of dendrimer generation, terminal group, and core chemistry. To gain insight into the mechanisms of HSA binding to PAMAM dendrimers, we combined (1)H NMR, saturation transfer difference (STD) NMR, and NMR diffusion ordered spectroscopy (DOSY) of dendrimer-HSA complexes with atomistic molecular dynamics (MD) simulations of dendrimer conformation in aqueous solutions. The binding measurements show that the HSA binding constants (K(b)) of PAMAM dendrimers depend on dendrimer size and terminal group chemistry. The NMR (1)H and DOSY experiments indicate that the interactions between HSA and PAMAM dendrimers are relatively weak. The (1)H NMR STD experiments and MD simulations suggest that the inner shell protons of the dendrimers groups interact more strongly with HSA proteins. These interactions, which are consistently observed for different dendrimer generations (G0-NH(2)vs G4-NH(2)) and terminal groups (G4-NH(2)vs G4-OH with amidoethanol groups), suggest that PAMAM dendrimers adopt backfolded configurations as they form weak complexes with HSA proteins in aqueous solutions at physiological pH (7.4).

  15. Synthesis and Catalytic Evaluation of Dendrimer-Encapsulated Cu Nanoparticles: An Undergraduate Experiment Exploring Catalytic Nanomaterials

    Science.gov (United States)

    Feng, Z. Vivian; Lyon, Jennifer L.; Croley, J. Sawyer; Crooks, Richard M.; Vanden Bout, David A.; Stevenson, Keith J.

    2009-01-01

    Copper nanoparticles were synthesized using generation 4 hydroxyl-terminated (G4-OH) poly(amidoamine) (PAMAM) dendrimers as templates. The synthesis is conducted by coordinating copper ions with the interior amines of the dendrimer, followed by chemical reduction to form dendrimer-encapsulated copper nanoparticles (Cu-DEN). The catalytic…

  16. Families of Meromorphic Multivalent Functions Associated with the Dziok-Raina Operator

    Directory of Open Access Journals (Sweden)

    G. Murugusundaramoorthy

    2013-07-01

    Full Text Available Making use a linear operator, which is defined here by means of the Hadamard product (or convolution, involving the Wright’s generalized hypergeometric function , we introduce two novel subclassesP p(q,s,α1;A,B,λ andP+p(q,s,α1;A,B,λ of meromorphically multivalent functions oforder λ(0 ≤ λ < p in the punctured disc U∗. In this paper we investigate the various important properties and characteristics of these subclasses of meromorphically multivalent functions. We extend the familiar concept of neighborhoods of analytic functions to these subclasses of meromorphically multivalent functions . We also derive many interesting results for the Hadamard products of functions belonging to the classP+p(q,s,α1;A,B,λ.

  17. Interactions between similar and dissimilar charged interfaces in the presence of multivalent anions.

    Science.gov (United States)

    Moazzami-Gudarzi, Mohsen; Adam, Pavel; Smith, Alexander M; Trefalt, Gregor; Szilágyi, István; Maroni, Plinio; Borkovec, Michal

    2018-04-04

    Direct force measurements involving amidine latex (AL) and sulfate latex (SL) particles in aqueous solutions containing multivalent ferrocyanide anions are presented. These measurements feature three different pairs of particles, namely SL-SL, AL-SL, and AL-AL. The force profiles are quantitatively interpreted in terms of the theory by Derjaguin, Landau, Verwey, and Overbeek (DLVO) that is combined with a short-ranged exponential attraction. In monovalent salt solutions, the AL particles are positively charged, while the SL particles are negatively charged. In solutions containing ferrocyanide, the charge of the AL particles is reversed as the concentration is increased. The longer-ranged component of all force profiles is fully compatible with DLVO theory, provided effects of charge regulation are included. At shorter distances, an additional exponential attraction must be introduced, whereby the respective decay length is about 2 nm for the AL-AL pair, and below 1 nm for the SL-SL pair. This non-DLVO force is intermediate for the asymmetric AL-SL pair. These additional forces are probably related to charge fluctuations, patch-charged interactions, or hydrophobic forces.

  18. Immobilization of alginate-encapsulated Bacillus thuringiensis var. israelensis containing different multivalent counterions for mosquito control.

    Science.gov (United States)

    Prabakaran, G; Hoti, S L

    2008-08-01

    Immobilized techniques have been used widely for the controlled release formulation of mosquitoes. Among the microbial formulations, polymeric matrices play an important role in the controlled release of microbial pesticide at rates sufficiently effective to kill mosquitoes in the field. The advantage of these matrices is that they enhance the stability of both spores and toxin against pH, temperature variations, and UV irradiation. The disadvantage of using calcium alginate beads is that they are unstable upon contact with phosphate of potassium or sodium ions rich in the mosquito habitats. To overcome these problems, attempts were made to encapsulate Bacillus thuringiensis var. israelensis within alginate by using different multivalent counterions, namely, calcium chloride, zinc sulfate, copper sulfate, cobalt chloride, and ferric chloride, and the beads formed were tested for its mosquito larvicidal activity. Among all the beads tested, zinc alginate beads resulted in maximum larvicidal activity of 98% (+/-1.40 SE) against Culex quinquefasciatus IIIrd instar larvae and maximum spore count of 3.36 x 10(5) (+/-5291.50 SE) CFU/ml. Zinc alginate beads maintained their structure for up to 48 h when shaken vigorously on a rotary shaker at 180 rpm in the presence of 10 mM potassium phosphate buffer (pH 6.8 +/- 0.1). In conclusion, our results suggest that the use of zinc sulfate as counterions to encapsulate B. thuringiensis var. israelensis within alginate may be a potent mosquito control program in the habitats where more phosphate ions are present.

  19. Reaction enthalpy from the binding of multivalent cations to anionic polyelectrolytes in dilute solutions

    Science.gov (United States)

    Hansch, Markus; Kaub, Hans Peter; Deck, Sascha; Carl, Nico; Huber, Klaus

    2018-03-01

    Dilute solutions of sodium poly(styrene sulfonate) (NaPSS) in the presence of Al3+, Ca2+, and Ba2+ were analysed by means of isothermal titration calorimetry (ITC) in order to investigate the heat effect of bond formation between those cations and the anionic SO3- residues of NaPSS. The selection of the cations was guided by the solution behavior of the corresponding PSS salts from a preceding study [M. Hansch et al., J. Chem. Phys. 148(1), 014901 (2018)], where bonds between Ba2+ and anionic PSS showed an increasing solubility with decreasing temperature and Al3+ exhibited the inverse trend. Unlike to Al3+ and Ba2+, Ca2+ is expected to behave as a purely electrostatically interacting bivalent cation and was thus included in the present study. Results from ITC satisfactorily succeeded to explain the temperature-dependent solution behavior of the salts with Al3+ and Ba2+ and confirmed the non-specific behavior of Ca2+. Additional ITC experiments with salts of Ca2+ and Ba2+ and sodium poly(acrylate) complemented the results on PSS by data from a chemically different polyanion. Availability of these joint sets of polyanion-cation combinations not only offers the chance to identify common features and subtle differences in the solution behavior of polyelectrolytes in the presence of multi-valent cations but also points to a new class of responsive materials.

  20. Tunable Graphitic Carbon Nano-Onions Development in Carbon Nanofibers for Multivalent Energy Storage

    Energy Technology Data Exchange (ETDEWEB)

    Schwarz, Haiqing L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2016-01-01

    We developed a novel porous graphitic carbon nanofiber material using a synthesis strategy combining electrospinning and catalytic graphitization. RF hydrogel was used as carbon precursors, transition metal ions were successfully introduced into the carbon matrix by binding to the carboxylate groups of a resorcinol derivative. Transition metal particles were homogeneously distributed throughout the carbon matrix, which are used as in-situ catalysts to produce graphitic fullerene-like nanostructures surrounding the metals. The success design of graphitic carbons with enlarged interlayer spacing will enable the multivalent ion intercalation for the development of multivalent rechargeable batteries.

  1. 6-Azido hyacinthacine A2 gives a straightforward access to the first multivalent pyrrolizidine architectures.

    Science.gov (United States)

    D'Adamio, Giampiero; Parmeggiani, Camilla; Goti, Andrea; Moreno-Vargas, Antonio J; Moreno-Clavijo, Elena; Robina, Inmaculada; Cardona, Francesca

    2014-08-28

    The synthesis of the first multivalent pyrrolizidine iminosugars is reported. The key azido intermediates 4 and 31 were prepared after suitable synthetic elaboration of the cycloadduct obtained from 1,3-dipolar cycloaddition of D-arabinose derived nitrone to dimethylacrylamide. The key step of the strategy was the stereoselective installation of an azido moiety at C-6 of the pyrrolizidine skeleton. The click reaction with different monovalent and dendrimeric alkyne scaffolds allowed the preparation of a library of new mono- and multivalent pyrrolizidine compounds that were preliminarily assayed as glycosidase inhibitors towards a panel of commercially available glycosyl hydrolases.

  2. Dendrimers: relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of 125I-labelled polyamidoamine dendrimers in vivo.

    Science.gov (United States)

    Malik, N; Wiwattanapatapee, R; Klopsch, R; Lorenz, K; Frey, H; Weener, J W; Meijer, E W; Paulus, W; Duncan, R

    2000-03-01

    Dendrimers are highly branched macromolecules of low polydispersity that provide many exciting opportunities for design of novel drug-carriers, gene delivery systems and imaging agents. They hold promise in tissue targeting applications, controlled drug release and moreover, their interesting nanoscopic architecture might allow easier passage across biological barriers by transcytosis. However, from the vast array of structures currently emerging from synthetic chemistry it is essential to design molecules that have real potential for in vivo biological use. Here, polyamidoamine (PAMAM, Starburst), poly(propyleneimine) with either diaminobutane or diaminoethane as core, and poly(ethylene oxide) (PEO) grafted carbosilane (CSi-PEO) dendrimers were used to study systematically the effect of dendrimer generation and surface functionality on biological properties in vitro. Generally, dendrimers bearing -NH(2) termini displayed concentration- and in the case of PAMAM dendrimers generation-dependent haemolysis, and changes in red cell morphology were observed after 1 h even at low concentrations (10 microg/ml). At concentrations below 1 mg/ml CSi-PEO dendrimers and those dendrimers with carboxylate (COONa) terminal groups were neither haemolytic nor cytotoxic towards a panel of cell lines in vitro. In general, cationic dendrimers were cytotoxic (72 h incubation), displaying IC(50) values=50-300 microg/ml dependent on dendrimer-type, cell-type and generation. Preliminary studies with polyether dendrimers prepared by the convergent route showed that dendrimers with carboxylate and malonate surfaces were not haemolytic at 1 h, but after 24 h, unlike anionic PAMAM dendrimers they were lytic. Cationic 125I-labelled PAMAM dendrimers (gen 3 and 4) administered intravenously (i.v.) to Wistar rats ( approximately 10 microg/ml) were cleared rapidly from the circulation (<2% recovered dose in blood at 1 h). Anionic PAMAM dendrimers (gen 2.5, 3.5 and 5.5) showed longer circulation

  3. The application of poly(amidoamine dendrimers for modification of jute yarns: Preparation and dyeing properties

    Directory of Open Access Journals (Sweden)

    Ali Akbar Zolriasatein

    2015-03-01

    Full Text Available In this study, poly(amidoamine (PAMAM G-2 dendrimer was used for jute yarn. Fourier transform infrared spectroscopy (FT-IR revealed that all carbonyl groups of jute fibers reacted with amino groups of polyamidoamine dendrimers. SEM observation indicated the good dispersion PAMAM dendrimers. Jute yarns pretreated with PAMAM dendrimer displayed markedly enhanced color strength with reactive dyes, even when dyeing had been carried out in the absence of electrolyte or alkali. Dendrimer-treated jute yarn showed much better light-fastness than untreated jute yarn.

  4. Transepithelial Transport of PEGylated Anionic Poly(amidoamine) Dendrimers: Implications for Oral Drug Delivery

    OpenAIRE

    Sweet, Deborah M.; Kolhatkar, Rohit B.; Ray, Abhijit; Swaan, Peter; Ghandehari, Hamidreza

    2009-01-01

    The purpose of this work was to assess the impact of PEGylation on transepithelial transport of anionic poly(amidoamine) dendrimers. Cytotoxicity, uptake and transport across Caco-2 cells of PEGylated G3.5 and G4.5 PAMAM dendrimers were studied. Methoxy polyethylene glycol (750 Da) was conjugated to carboxylic acid-terminated PAMAM dendrimers at feed ratios of 1, 2 and 4 PEG per dendrimer. Compared to the control, PEGylation of anionic dendrimers did not significantly alter cytotoxicity up to...

  5. Energy transfer dynamics in Light-Harvesting Dendrimers

    Science.gov (United States)

    Melinger, Joseph S.; McMorrow, Dale; Kleiman, Valeria D.

    2002-03-01

    We explore energy transfer dynamics in light-harvesting phenylacetylene symmetric and asymmetric dendrimers. Femtosecond pump-probe spectroscopy is used to probe the ultrafast dynamics of electronic excitations in these dendrimers. The backbone of the macromolecule consists of branches of increasing conjugation length, creating an energy gradient, which funnels energy to an accepting perylene trap. In the case of the symmetric dendrimer (nanostar), the energy transfer efficiency is known to approach nearly unity, although the nature and timescale of the energy transfer process is still unknown. For the asymmetric dendrimers, energy transfer efficiencies are very high, with the possibility of more complex transfer processes. We experimentally monitor the transport of excitons through the light-harvesting dendrimer. The transients show a number of components, with timescales ranging from <300fs to several tens of picoseconds, revealing the complex photophysics taking place in these macromolecules. We interpret our results in terms of the Förster mechanism in which energy transfer occurs through dipole-dipole interactions.

  6. Cationic PAMAM dendrimers as pore-blocking binary toxin inhibitors.

    Science.gov (United States)

    Förstner, Philip; Bayer, Fabienne; Kalu, Nnanya; Felsen, Susanne; Förtsch, Christina; Aloufi, Abrar; Ng, David Y W; Weil, Tanja; Nestorovich, Ekaterina M; Barth, Holger

    2014-07-14

    Dendrimers are unique highly branched macromolecules with numerous groundbreaking biomedical applications under development. Here we identified poly(amido amine) (PAMAM) dendrimers as novel blockers for the pore-forming B components of the binary anthrax toxin (PA63) and Clostridium botulinum C2 toxin (C2IIa). These pores are essential for delivery of the enzymatic A components of the internalized toxins from endosomes into the cytosol of target cells. We demonstrate that at low μM concentrations cationic PAMAM dendrimers block PA63 and C2IIa to inhibit channel-mediated transport of the A components, thereby protecting HeLa and Vero cells from intoxication. By channel reconstitution and high-resolution current recording, we show that the PAMAM dendrimers obstruct transmembrane PA63 and C2IIa pores in planar lipid bilayers at nM concentrations. These findings suggest a new potential role for the PAMAM dendrimers as effective polyvalent channel-blocking inhibitors, which can protect human target cells from intoxication with binary toxins from pathogenic bacteria.

  7. Transepithelial Transport of PAMAM Dendrimers Across Isolated Human Intestinal Tissue.

    Science.gov (United States)

    Hubbard, Dallin; Enda, Michael; Bond, Tanner; Moghaddam, Seyyed Pouya Hadipour; Conarton, Josh; Scaife, Courtney; Volckmann, Eric; Ghandehari, Hamidreza

    2015-11-02

    Poly(amido amine) (PAMAM) dendrimers have shown transepithelial transport across intestinal epithelial barrier in rats and across Caco-2 cell monolayers. Caco-2 models innately lack mucous barriers, and rat isolated intestinal tissue has been shown to overestimate human permeability. This study is the first report of transport of PAMAM dendrimers across isolated human intestinal epithelium. It was observed that FITC labeled G4-NH2 and G3.5-COOH PAMAM dendrimers at 1 mM concentration do not have a statistically higher permeability compared to free FITC controls in isolated human jejunum and colonic tissues. Mannitol permeability was increased at 10 mM concentrations of G3.5-COOH and G4-NH2 dendrimers. Significant histological changes in human colonic and jejunal tissues were observed at G3.5-COOH and G4-NH2 concentrations of 10 mM implying that dose limiting toxicity may occur at similar concentrations in vivo. The permeability through human isolated intestinal tissue in this study was compared to previous rat and Caco-2 permeability data. This study implicates that PAMAM dendrimer oral drug delivery may be feasible, but it may be limited to highly potent drugs.

  8. Mechanism of PAMAM Dendrimers Internalization in Hippocampal Neurons.

    Science.gov (United States)

    Vidal, Felipe; Vásquez, Pilar; Díaz, Carola; Nova, Daniela; Alderete, Joel; Guzmán, Leonardo

    2016-10-03

    Polyamidoamine (PAMAM) dendrimers are hyperbranched macromolecules which have been described as one of the most promising drug nanocarrier systems. A key process to understand is their cellular internalization mechanism because of its direct influence on their intracellular distribution, association with organelles, entry kinetics, and cargo release. Despite that internalization mechanisms of dendrimers have been studied in different cell types, in the case of neurons they are not completely described. Considering the relevance of central nervous system (CNS) diseases and neuropharmacology, the aim of this report is to describe the molecular internalization mechanism of different PAMAM-based dendrimer systems in hippocampal neurons. Four dendrimers based on fourth generation PAMAM with different surface properties were studied: unmodified G4, with a positively charged surface; PP50, with a substitution of the 50% of amino surface groups with polyethylene glycol neutral groups; PAc, with a substitution of the 30% of amino surface groups with acrylate anionic groups; and PFO, decorated with folic acid groups in a 25% of total terminal groups. Confocal images show that both G4 and PFO are able to enter the neurons, but not PP50 and PAc. Colocalization study with specific endocytosis markers and specific endocytosis inhibitor assay demonstrate that clathrin-mediated endocytosis would be the main internalization mechanism for G4, whereas clathrin- and caveolae-mediated endocytosis would be implicated in PFO internalization. These results show the existence of different internalization mechanisms for PAMAM dendrimers in neurons and the possibility to control their internalization properties with specific chemical modifications.

  9. Fluorescence Quenching of Dendrimer-Encapsulated CdS Quantum Dots for the Detection of H{sub 2}O{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Hyojung; Kim, Hai Dong; Kim, Joohoon [Kyung Hee Un iversity, Seoul (Korea, Republic of)

    2016-02-15

    Hydrogen peroxide (H{sub 2}O{sub 2}) exists in natural environments as a byproduct of various enzymatic and photochemical reactions. Various approaches have been reported for the synthesis of cadmium sulfide (CdS) QDs using dendrimers, which can be categorized mainly into two general approaches. The first approach utilizes dendrimers as capping agents, resulting in the formation of agglomerates of spatially segregated QDs stabilized by multiple dendrimers. We have described the synthesis and characterization of the CdS QDs using G6-NH{sub 2} dendrimers. By controlling the molar ratios (n = Cd2+/G6-NH{sub 2}) between the Cd{sup 2+} ions and G6-NH{sub 2} dendrimers, we synthesized a set of CdS QDs with different structural and optical properties. Importantly, the synthesized CdS QDs exhibited H{sub 2}O{sub 2}-sensitive fluorescence, which can be utilized for the detection of H{sub 2}O{sub 2}. Especially, the CdS QDs with n = 64 displayed a Stern–Volmer relationship between the fluorescence of the CdS QDs and the concentration of H{sub 2}O{sub 2}, as well as the strongest fluorescence among the set of the synthesized CdS QDs. Since core-shell structures of QDs often result in enhanced stability and quantum efficiency of the QDs, we are currently working on core-shell structured QDs prepared using dendrimers to improve their stability and quantum yield compared to the CdS QDs reported in the present study.

  10. Transepithelial transport of PEGylated anionic poly(amidoamine) dendrimers: implications for oral drug delivery.

    Science.gov (United States)

    Sweet, Deborah M; Kolhatkar, Rohit B; Ray, Abhijit; Swaan, Peter; Ghandehari, Hamidreza

    2009-08-19

    The purpose of this work was to assess the impact of PEGylation on transepithelial transport of anionic poly(amidoamine) dendrimers. Cytotoxicity, uptake and transport across Caco-2 cells of PEGylated G3.5 and G4.5 PAMAM dendrimers were studied. Methoxy polyethylene glycol (750 Da) was conjugated to carboxylic acid-terminated PAMAM dendrimers at feed ratios of 1, 2 and 4 PEG per dendrimer. Compared to the control, PEGylation of anionic dendrimers did not significantly alter cytotoxicity up to a concentration of 0.1 mM. PEGylation of G3.5 dendrimers significantly decreased cellular uptake and transepithelial transport while PEGylation of G4.5 dendrimers led to a significant increase in uptake, but also a significant decrease in transport. Dendrimer PEGylation reduced the opening of tight junctions as evidenced by confocal microscopy techniques. Modulation of the tight junctional complex correlated well with changes in PEGylated dendrimer transport and suggests that anionic dendrimers are transported primarily through the paracellular route. PEGylated dendrimers show promise in oral delivery applications where increased functionality for drug conjugation and release is desired.

  11. Molecular analysis of interactions between dendrimers and asymmetric membranes at different transport stages.

    Science.gov (United States)

    He, XiaoCong; Qu, ZhiGuo; Xu, Feng; Lin, Min; Wang, JiuLing; Shi, XingHua; Lu, TianJian

    2014-01-07

    Studying dendrimer-biomembrane interactions is important for understanding drug and gene delivery. In this study, coarse-grained molecular dynamics simulations were performed to investigate the behaviors of polyamidoamine (PAMAM) dendrimers (G4 and G5) as they interacted with asymmetric membranes from different sides of the bilayer, thus mimicking different dendrimer transport stages. The G4 dendrimer could insert into the membrane during an equilibrated state, and the G5 dendrimer could induce pore formation in the membrane when the dendrimers interacted with the outer side (outer interactions) of an asymmetric membrane [with 10% dipalmitoyl phosphatidylserine (DPPS) in the inner leaflet of the membrane]. During the interaction with the inner side of the asymmetric membrane (inner interactions), the G4 and G5 dendrimers only adsorbed onto the membrane. As the membrane asymmetry increased (e.g., increased DPPS percentage in the inner leaflet of the membrane), the G4 and G5 dendrimers penetrated deeper into the membrane during the outer interactions and the G4 and G5 dendrimers were adsorbed more tightly onto the membrane for the inner interactions. When the DPPS content reached 50%, the G4 dendrimer could completely penetrate through the membrane from the outer side to the inner side. Our study provides molecular understanding and reference information about different dendrimer transport stages during drug and gene delivery.

  12. Immobilization of dendrimers on Si-C linked carboxylic acid-terminated monolayers on silicon(111)

    International Nuclear Information System (INIS)

    Boecking, Till; Wong, Elicia L.S.; James, Michael; Watson, Jolanta A.; Brown, Christopher L.; Chilcott, Terry C.; Barrow, Kevin D.; Coster, Hans G.L.

    2006-01-01

    Poly(amidoamine) dendrimers were attached to activated undecanoic acid monolayers, covalently linked to smooth silicon surfaces via Si-C bonds. The resulting ultra-thin dendrimer films were characterized by X-ray photoelectron spectroscopy (XPS), X-ray reflectometry (XR) and atomic force microscopy (AFM). XPS results suggested amide bond formation between the dendrimer and the surface carboxylic acid groups. XR yielded thicknesses of 10 A for the alkyl region of the undecanoic acid monolayer and 12 A for the dendrimer layer, considerably smaller than the diameter of these spherical macromolecules in solution. This was consistent with AFM images showing collapsed dendrimers on the surface. It was concluded that the deformation arose from a large number of amine groups on the surface of each dendrimer reacting efficiently with the activated surface, whereby the dendrimers can deform to fill voids while spreading over the activated surface to form a homogeneous macromolecular layer

  13. Self-assembling multivalency : supramolecular polymers assembled from monovalent mannose-labelled discotic molecules

    NARCIS (Netherlands)

    Petkau - Milroy, K.; Brunsveld, L.

    2013-01-01

    Supramolecular synthesis, the "bottom-up" construction of higher-order structures from monomeric building blocks, represents a flexible approach for the generation of multivalent materials. Here, monovalent building blocks decorated with a single bioactive ligand were synthesized. In water, these

  14. New Dendrimer-Based Nanoparticles Enhance Curcumin Solubility.

    Science.gov (United States)

    Falconieri, Maria Cristina; Adamo, Mauro; Monasterolo, Claudio; Bergonzi, Maria Camilla; Coronnello, Marcella; Bilia, Anna Rita

    2017-03-01

    Curcumin, the main curcuminoid of the popular Indian spice turmeric, is a potent chemopreventive agent and useful in many different diseases. A major limitation of applicability of curcumin as a health promoting and medicinal agent is its extremely low bioavailability due to efficient first pass metabolism, poor gastrointestinal absorption, rapid elimination, and poor aqueous solubility. In the present study, nanotechnology was selected as a choice approach to enhance the bioavailability of the curcuminis. A new polyamidoamine dendrimer (G0.5) was synthesized, characterized, and tested for cytotoxicity in human breast cancer cells (MCF-7). No cytotoxicity of G0.5 was found in the range between 10 -3 and 3 × 10 -8  M. Consequently, G0.5 was used to prepare spherical nanoparticles of ca. 150 nm, which were loaded with curcumin [molar ratio G0.5/curcumin 1 : 1 (formulation 1) and 1 : 0.5 (formulation 2)]. Remarkably, the occurrence of a single population of nanoparticles having an excellent polydispersity index (solubility of curcumin was increased ca. 415 and 150 times with respect to the unformulated drug, respectively, for formulation 1 and formulation 2. The release of curcumin from the nanoparticles showed an interesting prolonged and sustained release profile. Georg Thieme Verlag KG Stuttgart · New York.

  15. Dendrimer-based biosensor for chemiluminescent detection of DNA hybridization

    International Nuclear Information System (INIS)

    Liu, P.; Hun, X.; Qing, H.

    2011-01-01

    We report on a highly sensitive chemiluminescent (CL) biosensor for the sequence-specific detection of DNA using a novel bio barcode DNA probe modified with gold nanoparticles that were covered with a dendrimer. The modified probe is composed of gold nanoparticles, a dendrimer, the CL reagent, and the DNA. The capture probe DNA was immobilized on magnetic beads covered with gold. It first hybridizes with the target DNA and then with one terminal end of the signal DNA on the barcoded DNA probe. CL was generated by adding H 2 O 2 and Co(II) ions as the catalyst. The immobilization of dendrimer onto the gold nanoparticles can significantly enhance sensitivity and gives a detection limit of 6 fmol L -1 of target DNA. (author)

  16. Recent Advances in Click Chemistry Applied to Dendrimer Synthesis

    Directory of Open Access Journals (Sweden)

    Mathieu Arseneault

    2015-05-01

    Full Text Available Dendrimers are monodisperse polymers grown in a fractal manner from a central point. They are poised to become the cornerstone of nanoscale devices in several fields, ranging from biomedicine to light-harvesting. Technical difficulties in obtaining these molecules has slowed their transfer from academia to industry. In 2001, the arrival of the “click chemistry” concept gave the field a major boost. The flagship reaction, a modified Hüisgen cycloaddition, allowed researchers greater freedom in designing and building dendrimers. In the last five years, advances in click chemistry saw a wider use of other click reactions and a notable increase in the complexity of the reported structures. This review covers key developments in the click chemistry field applied to dendrimer synthesis from 2010 to 2015. Even though this is an expert review, basic notions and references have been included to help newcomers to the field.

  17. On Topological Indices of Certain Families of Nanostar Dendrimers.

    Science.gov (United States)

    Husin, Mohamad Nazri; Hasni, Roslan; Arif, Nabeel Ezzulddin; Imran, Muhammad

    2016-06-24

    A topological index of graph G is a numerical parameter related to G which characterizes its molecular topology and is usually graph invariant. In the field of quantitative structure-activity (QSAR)/quantitative structure-activity structure-property (QSPR) research, theoretical properties of the chemical compounds and their molecular topological indices such as the Randić connectivity index, atom-bond connectivity (ABC) index and geometric-arithmetic (GA) index are used to predict the bioactivity of different chemical compounds. A dendrimer is an artificially manufactured or synthesized molecule built up from the branched units called monomers. In this paper, the fourth version of ABC index and the fifth version of GA index of certain families of nanostar dendrimers are investigated. We derive the analytical closed formulas for these families of nanostar dendrimers. The obtained results can be of use in molecular data mining, particularly in researching the uniqueness of tested (hyper-branched) molecular graphs.

  18. On Topological Indices of Certain Families of Nanostar Dendrimers

    Directory of Open Access Journals (Sweden)

    Mohamad Nazri Husin

    2016-06-01

    Full Text Available A topological index of graph G is a numerical parameter related to G which characterizes its molecular topology and is usually graph invariant. In the field of quantitative structure-activity (QSAR/quantitative structure-activity structure-property (QSPR research, theoretical properties of the chemical compounds and their molecular topological indices such as the Randić connectivity index, atom-bond connectivity (ABC index and geometric-arithmetic (GA index are used to predict the bioactivity of different chemical compounds. A dendrimer is an artificially manufactured or synthesized molecule built up from the branched units called monomers. In this paper, the fourth version of ABC index and the fifth version of GA index of certain families of nanostar dendrimers are investigated. We derive the analytical closed formulas for these families of nanostar dendrimers. The obtained results can be of use in molecular data mining, particularly in researching the uniqueness of tested (hyper-branched molecular graphs.

  19. Dendrimer-magnetic nanostructure: a Monte Carlo simulation

    Science.gov (United States)

    Jabar, A.; Masrour, R.

    2017-11-01

    In this paper, the magnetic properties of ternary mixed spins (σ,S,q) Ising model on a dendrimer nanostructure are studied using Monte Carlo simulations. The ground state phase diagrams of dendrimer nanostructure with ternary mixed spins σ = 1/2, S = 1 and q = 3/2 Ising model are found. The variation of the thermal total and partial magnetizations with the different exchange interactions, the external magnetic fields and the crystal fields have been also studied. The reduced critical temperatures have been deduced. The magnetic hysteresis cycles have been discussed. In particular, the corresponding magnetic coercive filed values have been deduced. The multiples hysteresis cycles are found. The dendrimer nanostructure has several applications in the medicine.

  20. Structural properties of star-like dendrimers in solution

    International Nuclear Information System (INIS)

    Rathgeber, S.; Gast, A.P.; Hedrick, J.L.

    2002-01-01

    We measured the form factor of star-like poly-ε-caprolactone dendrimers under good solvent conditions with small-angle neutron scattering (SANS). The parameters varied in the experiment were the dendrimer generation g=1,2,3 and the number of segments between the branching units n=5,10,15,20. The results are discussed in the frame work of the Beaucage model from which we cannot only derive the radius of gyration R g of the dendrimers but also their fractal dimensions. Decreasing the number of spacer units between the branching points results in a strong stretching of the dendrons. The fractal dimension increases monotonically with increasing generation and spacer number between the limit expected for a low-functionality star P∼5/3 (loose, polymeric structure) and that expected for a high-functionality star P∼3 (compact shape). (orig.)

  1. New organic photorefractive material composed of a charge-transporting dendrimer and a stilbene chromophore

    Science.gov (United States)

    Bai, Jaeil; Ducharme, Stephen; Leonov, Alexei G.; Lu, Liu; Takacs, James M.

    1999-10-01

    In this report, we introduce new organic photorefractive composites consisting of charge transporting den-drimers highly doped with a stilbene nonlinear optic chromophore, The purpose of making these composites is to improve charge transport, by reducing inhomogeneity when compared to ordinary polymer-based systems. Because the structure of this material gives us freedom to control the orientation of charge transport agents synthetically, we can study the charge transport mechanism more systematically than in polymers. We discuss this point and present the characterization results for this material.

  2. Impact of Dendrimers on Solubility of Hydrophobic Drug Molecules

    Directory of Open Access Journals (Sweden)

    Sonam Choudhary

    2017-05-01

    Full Text Available Adequate aqueous solubility has been one of the desired properties while selecting drug molecules and other bio-actives for product development. Often solubility of a drug determines its pharmaceutical and therapeutic performance. Majority of newly synthesized drug molecules fail or are rejected during the early phases of drug discovery and development due to their limited solubility. Sufficient permeability, aqueous solubility and physicochemical stability of the drug are important for achieving adequate bioavailability and therapeutic outcome. A number of different approaches including co-solvency, micellar solubilization, micronization, pH adjustment, chemical modification, and solid dispersion have been explored toward improving the solubility of various poorly aqueous-soluble drugs. Dendrimers, a new class of polymers, possess great potential for drug solubility improvement, by virtue of their unique properties. These hyper-branched, mono-dispersed molecules have the distinct ability to bind the drug molecules on periphery as well as to encapsulate these molecules within the dendritic structure. There are numerous reported studies which have successfully used dendrimers to enhance the solubilization of poorly soluble drugs. These promising outcomes have encouraged the researchers to design, synthesize, and evaluate various dendritic polymers for their use in drug delivery and product development. This review will discuss the aspects and role of dendrimers in the solubility enhancement of poorly soluble drugs. The review will also highlight the important and relevant properties of dendrimers which contribute toward drug solubilization. Finally, hydrophobic drugs which have been explored for dendrimer assisted solubilization, and the current marketing status of dendrimers will be discussed.

  3. Characterisation of immune responses in healthy foals when a multivalent vaccine protocol was initiated at age 90 or 180 days.

    Science.gov (United States)

    Davis, E G; Bello, N M; Bryan, A J; Hankins, K; Wilkerson, M

    2015-11-01

    Protection from infectious disease requires antigen-specific immunity. In foals, most vaccine protocols are delayed until 6 months to avoid maternal antibody interference. Susceptibility to disease may exist prior to administration of vaccination at age 4-6 months. The aim of this investigation was to characterise immune activation among healthy foals in response to a multivalent vaccine protocol and compare immune responses when foals were vaccinated at age either 90 or 180 days. Randomised block design. Twelve healthy foals with colostral transfer were blocked for age and randomly assigned to vaccination at age 90 days (treatment) or at age 180 days (control). Vaccination protocols included a 3-dose series and booster vaccine administered at age 11 months. Immune response following vaccination at age 90 or 180 days was comparable for several measures of cellular immunity. Antigen specific CD4+ and CD8+ expression of interleukin-4, interferon-γ and granzyme B to eastern equine encephalomyelitis, western equine encephalomyelitis, West Nile virus, tetanus toxoid, equine influenza and equine herpesvirus-1/4 antigens were evident for both groups 30 days after initial vaccine and at age 344 days. Both groups showed a significant increase in antigen-specific immunoglobulin G expression following booster vaccine at age 11 months, thereby indicating memory immune responses. The data presented in this report demonstrate that young foals are capable of immune activation following a 3-dose series with a multivalent vaccine, despite presence of maternal antibodies. Although immune activation does not automatically confer protection, several of the immune indicators measured showed comparable expression in foals vaccinated at 3 months relative to control foals vaccinated at age 6 months. In high-risk situations where immunity may be required earlier than following a conventional vaccine series, our data provide evidence that foals respond to immunisation initiated at 3 months

  4. Dendrimer-encapsulated nanoparticle-core micelles as a modular strategy for particle-in-a-box-in-a-box nanostructures

    NARCIS (Netherlands)

    Hove, ten J.B.; Wang, J.; Leeuwen, van F.W.B.; Velders, A.H.

    2017-01-01

    The hierarchically controlled synthesis and characterization of self-assembling macromolecules and particles are key to explore and exploit new nanomaterials. Here we present a versatile strategy for constructing particle-in-a-box-in-a-box systems by assembling dendrimer-encapsulated gold

  5. The neighbourhood polynomial of some families of dendrimers

    Science.gov (United States)

    Nazri Husin, Mohamad; Hasni, Roslan

    2018-04-01

    The neighbourhood polynomial N(G,x) is generating function for the number of faces of each cardinality in the neighbourhood complex of a graph and it is defined as (G,x)={\\sum }U\\in N(G){x}|U|, where N(G) is neighbourhood complex of a graph, whose vertices of the graph and faces are subsets of vertices that have a common neighbour. A dendrimers is an artificially manufactured or synthesized molecule built up from branched units called monomers. In this paper, we compute this polynomial for some families of dendrimer.

  6. Exciton localization-delocalization transition in an extended dendrimer

    Energy Technology Data Exchange (ETDEWEB)

    Pouthier, Vincent, E-mail: vincent.pouthier@univ-fcomte.fr [Institut UTINAM, Université de Franche-Comté, CNRS UMR 6213, 25030 Besançon Cedex (France)

    2013-12-21

    Exciton-mediated quantum state transfer between the periphery and the core of an extended dendrimer is investigated numerically. By mapping the dynamics onto that of a linear chain, it is shown that a localization-delocalization transition arises for a critical value of the generation number G{sub c} ≈ 5. This transition originates in the quantum interferences experienced by the excitonic wave due to the multiple scatterings that arise each time the wave tunnels from one generation to another. These results suggest that only small-size dendrimers could be used for designing an efficient quantum communication protocol.

  7. Exciton localization-delocalization transition in an extended dendrimer

    International Nuclear Information System (INIS)

    Pouthier, Vincent

    2013-01-01

    Exciton-mediated quantum state transfer between the periphery and the core of an extended dendrimer is investigated numerically. By mapping the dynamics onto that of a linear chain, it is shown that a localization-delocalization transition arises for a critical value of the generation number G c ≈ 5. This transition originates in the quantum interferences experienced by the excitonic wave due to the multiple scatterings that arise each time the wave tunnels from one generation to another. These results suggest that only small-size dendrimers could be used for designing an efficient quantum communication protocol

  8. M-Polynomial and Related Topological Indices of Nanostar Dendrimers

    Directory of Open Access Journals (Sweden)

    Mobeen Munir

    2016-09-01

    Full Text Available Dendrimers are highly branched organic macromolecules with successive layers of branch units surrounding a central core. The M-polynomial of nanotubes has been vastly investigated as it produces many degree-based topological indices. These indices are invariants of the topology of graphs associated with molecular structure of nanomaterials to correlate certain physicochemical properties like boiling point, stability, strain energy, etc. of chemical compounds. In this paper, we first determine M-polynomials of some nanostar dendrimers and then recover many degree-based topological indices.

  9. A multivalent Mannheimia-Bibersteinia vaccine protects bighorn sheep against Mannheimia haemolytica challenge.

    Science.gov (United States)

    Subramaniam, Renuka; Shanthalingam, Sudarvili; Bavananthasivam, Jegarubee; Kugadas, Abirami; Potter, Kathleen A; Foreyt, William J; Hodgins, Douglas C; Shewen, Patricia E; Barrington, George M; Knowles, Donald P; Srikumaran, Subramaniam

    2011-10-01

    Bighorn sheep (BHS) are more susceptible than domestic sheep (DS) to Mannheimia haemolytica pneumonia. Although both species carry M. haemolytica as a commensal bacterium in the nasopharynx, DS carry mostly leukotoxin (Lkt)-positive strains while BHS carry Lkt-negative strains. Consequently, antibodies to surface antigens and Lkt are present at much higher titers in DS than in BHS. The objective of this study was to determine whether repeated immunization of BHS with multivalent Mannheimia-Bibersteinia vaccine will protect them upon M. haemolytica challenge. Four BHS were vaccinated with a culture supernatant vaccine prepared from M. haemolytica serotypes A1 and A2 and Bibersteinia trehalosi serotype T10 on days 0, 21, 35, 49, and 77. Four other BHS were used as nonvaccinated controls. On the day of challenge, 12 days after the last immunization, the mean serum titers of Lkt-neutralizing antibodies and antibodies to surface antigens against M. haemolytica were 1:160 and 1:4,000, respectively. Following intranasal challenge with M. haemolytica A2 (1 × 10(5) CFU), all four control BHS died within 48 h. Necropsy revealed acute fibrinonecrotic pneumonia characteristic of M. haemolytica infection. None of the vaccinated BHS died during the 8 weeks postchallenge observation period. Radiography at 3 weeks postchallenge revealed no lung lesions in two vaccinated BHS and mild lesions in the other two, which resolved by 8 weeks postchallenge. These results indicate that if BHS can be induced to develop high titers of Lkt-neutralizing antibodies and antibodies to surface antigens, they are likely to survive M. haemolytica challenge which is likely to reduce the BHS population decline due to pneumonia.

  10. A Multivalent Mannheimia-Bibersteinia Vaccine Protects Bighorn Sheep against Mannheimia haemolytica Challenge ▿

    Science.gov (United States)

    Subramaniam, Renuka; Shanthalingam, Sudarvili; Bavananthasivam, Jegarubee; Kugadas, Abirami; Potter, Kathleen A.; Foreyt, William J.; Hodgins, Douglas C.; Shewen, Patricia E.; Barrington, George M.; Knowles, Donald P.; Srikumaran, Subramaniam

    2011-01-01

    Bighorn sheep (BHS) are more susceptible than domestic sheep (DS) to Mannheimia haemolytica pneumonia. Although both species carry M. haemolytica as a commensal bacterium in the nasopharynx, DS carry mostly leukotoxin (Lkt)-positive strains while BHS carry Lkt-negative strains. Consequently, antibodies to surface antigens and Lkt are present at much higher titers in DS than in BHS. The objective of this study was to determine whether repeated immunization of BHS with multivalent Mannheimia-Bibersteinia vaccine will protect them upon M. haemolytica challenge. Four BHS were vaccinated with a culture supernatant vaccine prepared from M. haemolytica serotypes A1 and A2 and Bibersteinia trehalosi serotype T10 on days 0, 21, 35, 49, and 77. Four other BHS were used as nonvaccinated controls. On the day of challenge, 12 days after the last immunization, the mean serum titers of Lkt-neutralizing antibodies and antibodies to surface antigens against M. haemolytica were 1:160 and 1:4,000, respectively. Following intranasal challenge with M. haemolytica A2 (1 × 105 CFU), all four control BHS died within 48 h. Necropsy revealed acute fibrinonecrotic pneumonia characteristic of M. haemolytica infection. None of the vaccinated BHS died during the 8 weeks postchallenge observation period. Radiography at 3 weeks postchallenge revealed no lung lesions in two vaccinated BHS and mild lesions in the other two, which resolved by 8 weeks postchallenge. These results indicate that if BHS can be induced to develop high titers of Lkt-neutralizing antibodies and antibodies to surface antigens, they are likely to survive M. haemolytica challenge which is likely to reduce the BHS population decline due to pneumonia. PMID:21832104

  11. Microfluidic biofunctionalisation protocols to form multi-valent interactions for cell rolling and phenotype modification investigations

    KAUST Repository

    Perozziello, Gerardo

    2013-07-01

    In this study, we propose a fast, simple method to biofunctionalise microfluidic systems for cellomic investigations based on micro-fluidic protocols. Many available processes either require expensive and time-consuming protocols or are incompatible with the fabrication of microfluidic systems. Our method differs from the existing since it is applicable to an assembled system, uses few microlitres of reagents and it is based on the use of microbeads. The microbeads have specific surface moieties to link the biomolecules and couple cell receptors. Furthermore, the microbeads serve as arm spacer and offer the benefit of the multi-valent interaction. Microfluidics was adapted together with topology and biochemistry surface modifications to offer the microenvironment for cellomic studies. Based on this principle, we exploit the streptavidin-biotin interaction to couple antibodies to the biofunctionalised microfluidic environment within 5 h using 200 μL of reagents and biomolecules. We selected the antibodies able to form complexes with the MHC class I (MHC-I) molecules present on the cell membrane and involved in the immune surveillance. To test the microfluidic system, tumour cell lines (RMA) were rolled across the coupled antibodies to recognise and strip MHC-I molecules. As result, we show that cell rolling performed inside a microfluidic chamber functionalised with beads and the opportune antibody facilitate the removal of MHC class I molecules. We showed that the level of median fluorescent intensity of the MHC-I molecules is 300 for cells treated in a not biofunctionalised surface. It decreased to 275 for cells treated in a flat biofunctionalised surface and to 250 for cells treated on a surface where biofunctionalised microbeads were immobilised. The cells with reduced expression of MHC-I molecules showed, after cytotoxicity tests, susceptibility 3.5 times higher than normal cells. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Synthesis of Poly(3,4,5-trihydroxybenzoate) dendrimers from Polyphenols and Their Chemiluminescence

    International Nuclear Information System (INIS)

    Jung, Dai Il; Song, Ju Hyun; Shin, Eun Hye; Kim, Yun Young; Lee, Do Hun; Choi, Soon Kyu; Hahn, Jung Tai

    2010-01-01

    Polyphenol dendrimers were synthesized to obtain a strong CL compound, and their CL intensities were found to be considerably stronger than the CL intensity of GA. The esterification of the hydroxyl groups of GA in the dendrimer was very effective in developing a strong CL. Further, the relationship between the CL intensity and structure of polyphenol dendrimers must be clarified to understand the reason behind the strong light emission of high-per-branch compounds such as poly(3,4,5-trihydroxybenzoate ester) dendrimers. Polyphenol CL dendrimers can be used for a wide variety of CL assays by utilizing the hydroxyl groups of the polyphenol for forming a hydrogen bond with oxygen in the analyte structure. Dendrimer chemistry is rapidly expanding both for fundamental reasons as well as due to requirements in technological applications. A recent interesting development in dendrimer chemistry concerns the coordination of metal ions by interior branches or exterior units. Dendrimers containing photoactive units are particularly interesting for two reasons: (1) cooperation among the photoactive components can allow the dendrimer to perform specific functions, and (2) changes in the properties of photoactive components can be exploited to monitor the participation of dendrimers in chemical processes

  13. Fabrication of dendrimer-releasing lipidic nanoassembly for cancer drug delivery.

    Science.gov (United States)

    Sun, Qihang; Ma, Xinpeng; Zhang, Bo; Zhou, Zhuxian; Jin, Erlei; Shen, Youqing; Van Kirk, Edward A; Murdoch, William J; Radosz, Maciej; Sun, Weilin

    2016-06-24

    An inherent dilemma in the use of nanomedicines for cancer drug delivery is their limited penetration into tumors due to their large size. We have demonstrated that dendrimer/lipid nanoassemblies can solve this problem by means of tumor-triggered disassembly and the release of small (several nanometers) dendrimers to facilitate tumor penetration. Herein, we report a general strategy for the fabrication of nanoassemblies from hydrophobic and hydrophilic dendrimers with phospholipids. Hydrophobic dendrimers could assemble with lipids via hydrophobic interactions, whereas hydrophilic dendrimers could only assemble with lipids in the presence of anionic surfactants via both electrostatic and hydrophobic interactions. The nanoassemblies of hydrophobic dendrimers/lipids were found to be capable of stripping off their lipid layers via fusion with the cell membrane and then intracellular or extracellular release of dendrimers, whereas the nanoassemblies of hydrophilic dendrimers/lipids were internalized via endocytosis and then released their dendrimers inside the cells. Therefore, these dendrimer/lipid nanoassemblies could be used for the delivery of different cancer drugs.

  14. Interaction of PAMAM dendrimers with bovine insulin depends on nanoparticle end-groups

    International Nuclear Information System (INIS)

    Nowacka, Olga; Milowska, Katarzyna; Bryszewska, Maria

    2015-01-01

    We have looked at the interactions between polyamidoamine (PAMAM) dendrimers with different terminal groups (−COOH, −NH 2 , −OH) and bovine insulin. The influence of PAMAM dendrimers on insulin was tested by measuring zeta potential and fluorescence quenching. The secondary structure of insulin in the presence of dendrimers was examined by circular dichroism. The effect of dendrimers on dithiotreitol-induced aggregation of insulin was investigated by spectrophotometry. Dendrimers quenched the fluorescence of insulin, but did not change its secondary structure. Thus dendrimers neither induce hormone aggregation nor inhibit the aggregation process induced by dithiotreitol (DTT), except at 0.01 µmol/l. Dendrimers–insulin interactions are mainly electrostatic. - Highlight: • The interactions between PAMAM dendrimers and insulin were investigated. • The PAMAM dendrimers can quench the fluorescence of insulin. • The PAMAM dendrimers did not change the secondary structure of insulin. • Dendrimers did not induce aggregation of hormone. • Dendrimers–insulin interaction is mainly electrostatic

  15. Dendrimers: a class of polymers in the nanotechnology for the delivery of active pharmaceuticals.

    Science.gov (United States)

    Samad, Abdus; Alam, Md Intakhab; Saxena, Kinshuk

    2009-01-01

    Dendrimers represent a class of novel polymers having unique molecular architectures characterized by their well-defined structure, with a high degree of molecular uniformity, low polydispersity and properties that make them attractive materials for the development of nanomedicines. The dendrimer drug delivery can be achieved by coupling a drug through one of two approaches. Hydrophobic drugs can be complexed within the hydrophobic dendrimer interior to make them water-soluble or drugs can be covalently coupled onto the surface of the dendrimer. In addition, dendrimers have been shown to be capable of bypassing efflux transporters. A new generation of dendrimer-based delivery systems will enable the efficient transport of drugs across cellular barriers. This review deals principally with the synthesis, characterization and recent applications of dendrimers. In future it will only ever be possible to designate a dendrimer as safe means of drug delivery related to a specific application. However, so far limited clinical experience using dendrimers makes it impossible to designate any particular system which is safe and non toxic. Although there is widespread concern as to the safety of nanosized particles, preclinical and clinical experience gained during the development of polymeric excipients, biomedical polymers and polymer therapeutics showed that judicious development of dendrimer chemistry for each specific application will ensure development of safe and important materials for biomedical and pharmaceutical use.

  16. SANS contrast variation on a dendrimer host-guest complex

    NARCIS (Netherlands)

    Kleppinger, R.; Mortensen, K.; Meijer, E.W.

    2002-01-01

    Small-angle neutron scattering (SANS) technique was used to study the configurational changes in an oligoethyleneoxy-functionalized poly(propyleneimine) dendrimer (host) when forming complexes with rose bengal (guest). Guinier fits to the scattering data recorded at max. contrast indicated a

  17. Interaction of porphyrins with PAMAM dendrimers in aqueous solution

    Czech Academy of Sciences Publication Activity Database

    Kubát, Pavel; Lang, Kamil; Zelinger, Zdeněk

    2007-01-01

    Roč. 131, - (2007), s. 200-205 ISSN 0167-7322 R&D Projects: GA ČR GA203/04/0426 Institutional research plan: CEZ:AV0Z40400503; CEZ:AV0Z40320502 Keywords : porphyrin * PAMAM dendrimer * aggragation Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 0.982, year: 2007

  18. Charge and energy transports via poly-phenylacetylene based dendrimers

    Science.gov (United States)

    Shin, Yongwoo; Li, Minghai; Lin, Xi

    2010-03-01

    Poly-Phenylacetylene (PPA) is widely used in photoconductivity, photoluminescence, and light harvesting applications. In this work, we investigate the charge and exciton transport energetics and mechanisms in the PPA-based dendrimers using our recently developed adapted Su-Schrieffer-Heeger (SSH) model Hamiltonians and ab initio Hartree-Fock (HF) calculations. We found both doping and photo-excitation lead to the formation of optical phonon dressed pi electron states, namely the self-localized polarons, in the energy gap. Independent from their origins, these polarons can be self-trapped at multiple lattice locations along the PPA chain, and migrate from one to the next with an activation barrier of ˜0.006 eV, slightly higher than the corresponding barrier found in trans-polyacetylene. The PPA-based dendrimers can be constructed via the meta-positions of phenyl rings. In this case, we found the dendrimer junctions form attractive potential wells for both polarons and excitons, and the width and height of these junction potential wells can be controlled by the geometry of the dendrimers.

  19. Complexing Methylene Blue with Phosphorus Dendrimers to Increase Photodynamic Activity

    Directory of Open Access Journals (Sweden)

    Monika Dabrzalska

    2017-02-01

    Full Text Available The efficiency of photodynamic therapy is limited mainly due to low selectivity, unfavorable biodistribution of photosensitizers, and long-lasting skin sensitivity to light. However, drug delivery systems based on nanoparticles may overcome the limitations mentioned above. Among others, dendrimers are particularly attractive as carriers, because of their globular architecture and high loading capacity. The goal of the study was to check whether an anionic phosphorus dendrimer is suitable as a carrier of a photosensitizer—methylene blue (MB. As a biological model, basal cell carcinoma cell lines were used. We checked the influence of the MB complexation on its singlet oxygen production ability using a commercial fluorescence probe. Next, cellular uptake, phototoxicity, reactive oxygen species (ROS generation, and cell death were investigated. The MB-anionic dendrimer complex (MB-1an was found to generate less singlet oxygen; however, the complex showed higher cellular uptake and phototoxicity against basal cell carcinoma cell lines, which was accompanied with enhanced ROS production. Owing to the obtained results, we conclude that the photodynamic activity of MB complexed with an anionic dendrimer is higher than free MB against basal cell carcinoma cell lines.

  20. Dendrimer-coated magnetic particles for radionuclide separation

    NARCIS (Netherlands)

    Grüttner, Cordula; Böhmer, Volker; Casnati, Alessandro; Dozol, Jean-Francois; Reinhoudt, David; Reinoso garcia, M.M.; Rudershausen, Sandra; Teller, Joachim; Ungaro, Rocco; Verboom, Willem; Wang, Pingshan

    2005-01-01

    Magnetic particles were synthesised for radionuclide removal from nuclear wastes by magnetic separation. Dendrimers with terminal amino groups attached to the particle surface were used to bind chelating groups for lanthanides and actinides. This led to a 50–400-fold increase of the distribution

  1. Dendrimer and an active substance occluded in the dendrimer : a process for the preparation thereof and a process for releasing the active substance

    NARCIS (Netherlands)

    1998-01-01

    The invention relates to a dendrimer composition in which an effective number of the terminal functionalities are provided with blocking agents, and at least one active substance species is occluded in the dendrimer. A blocking agent is a sufficiently sterically sized compound which readily enters

  2. Host-guest chemistry of dendrimer-drug complexes. 2. Effects of molecular properties of guests and surface functionalities of dendrimers.

    Science.gov (United States)

    Hu, Jingjing; Cheng, Yiyun; Wu, Qinglin; Zhao, Libo; Xu, Tongwen

    2009-08-06

    The host-guest chemistry of dendrimer-drug complexes is investigated by NMR techniques, including (1)H NMR and 2D-NOESY studies. The effects of molecular properties of drug molecules (protonation ability and spatial steric hindrance of charged groups) and surface functionalities of dendrimers (positively charged amine groups and negatively charged carboxylate groups) on the host-guest interactions are discussed. Different interaction mechanisms between dendrimers and drug molecules are proposed on the basis of NMR results. Primary amine- and secondary amine-containing drugs preferentially bind to negatively charged dendrimers by strong electrostatic interactions, whereas tertiary amine and quaternary ammonium-containing drugs have weak binding ability with dendrimers due to relatively low protonation ability of the tertiary amine group and serious steric hindrance of the quaternary ammonium group. Positively charged drugs locate only on the surface of negatively charged dendrimers, whereas negatively charged drugs locate both on the surface and in the interior cavities of positively charged dendrimers. The host-guest chemistry of dendrimer-drug complexes is promising for the development of new drug delivery systems.

  3. The synthesis and characterization of biotin-silver-dendrimer nanocomposites as novel bioselective labels

    Energy Technology Data Exchange (ETDEWEB)

    Maly, J; Lampova, H; Semeradtova, A; Stofik, M [Faculty of Science, University of J E Purkynje, 40096 Usti nad Labem (Czech Republic); Kovacik, L, E-mail: malyjalga@seznam.c [Institute of Cellular Biology and Pathology, First Faculty of Medicine, Charles University in Prague (Czech Republic)

    2009-09-23

    This paper presents a synthesis of a novel nanoparticle label with selective biorecognition properties based on a biotinylated silver-dendrimer nanocomposite (AgDNC). Two types of labels, a biotin-AgDNC (bio-AgDNC) and a biotinylated AgDNC with a poly(ethylene)glycol spacer (bio-PEG-AgDNC), were synthesized from a generation 7 (G7) hydroxyl-terminated ethylenediamine-core-type (2-carbon core) PAMAM dendrimer (DDM) by an N,N'-dicyclohexylcarbodiimide (DDC) biotin coupling and a NaBH{sub 4} silver reduction method. Synthesized conjugates were characterized by several analytical methods, such as UV-vis, FTIR, AFM, TEM, ELISA, HABA assay and SPR. The results show that stable biotinylated nanocomposites can be formed either with internalized silver nanoparticles (AgNPs) in a DMM polymer backbone ('type I') or as externally protected ('type E'), depending on the molar ratio of the silver/DMM conjugate and type of conjugate. Furthermore, the selective biorecognition function of the biotin is not affected by the AgNPs' synthesis step, which allows a potential application of silver nanocomposite conjugates as biospecific labels in various bioanalytical assays, or potentially as fluorescence cell biomarkers. An exploitation of the presented label in the development of electrochemical immunosensors is anticipated.

  4. Extremely efficient catalysis of carbon-carbon bond formation using "click" dendrimer-stabilized palladium nanoparticles.

    Science.gov (United States)

    Astruc, Didier; Ornelas, Cátia; Diallo, Abdou K; Ruiz, Jaime

    2010-07-20

    This article is an account of the work carried out in the authors' laboratory illustrating the usefulness of dendrimer design for nanoparticle palladium catalysis. The "click" synthesis of dendrimers constructed generation by generation by 1-->3 C connectivity, introduces 1,2,3-triazolyl ligands insides the dendrimers at each generation. Complexation of the ligands by Pd(II) followed by reduction to Pd(0) forms dendrimer-stabilized Pd nanoparticles (PdNPs) that are extremely reactive in the catalysis of olefin hydrogenation and C-C bond coupling reactions. The stabilization can be outer-dendritic for the small zeroth-generation dendrimer or intra-dendritic for the larger first- and second-generation dendrimers. The example of the Miyaura-Suzuki reaction that can be catalyzed by down to 1 ppm of PdNPs with a "homeopathic" mechanism (the less, the better) is illustrated here, including catalysis in aqueous solvents.

  5. Interaction of phosphorus dendrimers with HIV peptides—Fluorescence studies of nano-complexes formation

    Energy Technology Data Exchange (ETDEWEB)

    Ciepluch, Karol, E-mail: ciepluch@biol.uni.lodz.pl [Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska Street 141/143, 90-236 Lodz (Poland); Ionov, Maksim [Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska Street 141/143, 90-236 Lodz (Poland); Majoral, Jean-Pierre [Laboratoire de Chimie de Coordination du CNRS (LCC), 205 Route de Narbonne, F-31077 Toulouse cedex 4 (France); Muñoz-Fernández, Maria Angeles [Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid (Spain); Bryszewska, Maria [Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska Street 141/143, 90-236 Lodz (Poland)

    2014-04-15

    In this study, dendrimers emerge as an alternative approach for delivery of HIV peptides to dendritic cells. Gp160, NH-EIDNYTNTIYTLLEE-COOH; P24, NH-DTINEEAAEW-COOH and Nef, NHGMDDPEREVLEWRFDSRLAF-COOH peptides were complexed with two types of positively charged phosphorus-containing dendrimers (CPD). Fluorescence polarization, dynamic light scattering, transmission and electron microscopy (TEM) techniques were chosen to evaluate the dendriplexes stability. We were able to show that complexes were stable in time and temperature. This is crucial for using these peptide/dendrimer nano-complexes in a new vaccine against HIV-1 infection. -- Highlights: • The phosphorus dendrimers as nanocarriers of HIV-peptides are proposed. • The complexes of dendrimers and HIV-peptides were stable in time, temperature. • The results convince that phosphorus dendrimers could be consider as anti-HIV vaccine candidates.

  6. Interaction of phosphorus dendrimers with HIV peptides—Fluorescence studies of nano-complexes formation

    International Nuclear Information System (INIS)

    Ciepluch, Karol; Ionov, Maksim; Majoral, Jean-Pierre; Muñoz-Fernández, Maria Angeles; Bryszewska, Maria

    2014-01-01

    In this study, dendrimers emerge as an alternative approach for delivery of HIV peptides to dendritic cells. Gp160, NH-EIDNYTNTIYTLLEE-COOH; P24, NH-DTINEEAAEW-COOH and Nef, NHGMDDPEREVLEWRFDSRLAF-COOH peptides were complexed with two types of positively charged phosphorus-containing dendrimers (CPD). Fluorescence polarization, dynamic light scattering, transmission and electron microscopy (TEM) techniques were chosen to evaluate the dendriplexes stability. We were able to show that complexes were stable in time and temperature. This is crucial for using these peptide/dendrimer nano-complexes in a new vaccine against HIV-1 infection. -- Highlights: • The phosphorus dendrimers as nanocarriers of HIV-peptides are proposed. • The complexes of dendrimers and HIV-peptides were stable in time, temperature. • The results convince that phosphorus dendrimers could be consider as anti-HIV vaccine candidates

  7. Electrostatic Swelling and Conformational Variation Observed in High-Generation Polyelectrolyte Dendrimers

    International Nuclear Information System (INIS)

    Butler, Paul D.; Chen, Wei-Ren; Herwig, Kenneth W.; Hong, Kunlun; Liu, Yun; Porcar, L.; Shew, Chwen-Yang; Smith, Gregory Scott; Chen, Hsin-Lung; Chen, Chun-Yu; Li, Xin; Liu, Emily

    2010-01-01

    A coordinated study combining small angle neutron scattering (SANS) and small angle x-ray scattering (SAXS) measurements was conducted to investigate the structural characteristics of aqueous (D2O) generation 7 and 8 (G7 and G8) PAMAM dendrimer solutions as a function of molecular protonation at room temperature. The change in intra-molecular conformation was clearly exhibited in the data analysis by separating the variation in the inter-molecular correlation. Our results unambiguously demonstrate an increased molecular size and evolved intra-molecular density profile upon increasing the molecular protonation. This is contrary to the existing understanding that in higher generation polyelectrolyte dendrimers, steric crowding stiffens the local motion of dendrimer segments exploring additional available intra-dendrimer volume and therefore inhibits the electrostatic swelling. Our observation is relevant to elucidation of the general microscopic picture of polyelectrolyte dendrimer structure, as well as the development of dendrimer-based packages with based on the stimuli-responsive principle.

  8. pH controlled gating of toxic protein pores by dendrimers

    Science.gov (United States)

    Mandal, Taraknath; Kanchi, Subbarao; Ayappa, K. G.; Maiti, Prabal K.

    2016-06-01

    Designing effective nanoscale blockers for membrane inserted pores formed by pore forming toxins, which are expressed by several virulent bacterial strains, on a target cell membrane is a challenging and active area of research. Here we demonstrate that PAMAM dendrimers can act as effective pH controlled gating devices once the pore has been formed. We have used fully atomistic molecular dynamics (MD) simulations to characterize the cytolysin A (ClyA) protein pores modified with fifth generation (G5) PAMAM dendrimers. Our results show that the PAMAM dendrimer, in either its protonated (P) or non-protonated (NP) states can spontaneously enter the protein lumen. Protonated dendrimers interact strongly with the negatively charged protein pore lumen. As a consequence, P dendrimers assume a more expanded configuration efficiently blocking the pore when compared with the more compact configuration adopted by the neutral NP dendrimers creating a greater void space for the passage of water and ions. To quantify the effective blockage of the protein pore, we have calculated the pore conductance as well as the residence times by applying a weak force on the ions/water. Ionic currents are reduced by 91% for the P dendrimers and 31% for the NP dendrimers. The preferential binding of Cl- counter ions to the P dendrimer creates a zone of high Cl- concentration in the vicinity of the internalized dendrimer and a high concentration of K+ ions in the transmembrane region of the pore lumen. In addition to steric effects, this induced charge segregation for the P dendrimer effectively blocks ionic transport through the pore. Our investigation shows that the bio-compatible PAMAM dendrimers can potentially be used to develop therapeutic protocols based on the pH sensitive gating of pores formed by pore forming toxins to mitigate bacterial infections.Designing effective nanoscale blockers for membrane inserted pores formed by pore forming toxins, which are expressed by several virulent

  9. Solubility improvement of an anthelmintic benzimidazole carbamate by association with dendrimers

    Directory of Open Access Journals (Sweden)

    L. Fernández

    2011-12-01

    Full Text Available The improvement of aqueous solubility of methyl (5-[propylthio]-1H-benzimidazol-2-yl carbamate, albendazole (ABZ using polyamidoamine (PAMAM dendrimers as solubility enhancers was investigated. Full generation PAMAM dendrimers with amine terminal groups, (G3, with hydroxyl terminal groups (G3OH and half generation PAMAM dendrimers with carboxylate terminal groups (G2.5 and G3.5, were chosen for this study. The nature of dendrimer-ABZ association was investigated by UV absorption, fluorescence emission measurements and by ¹H-NMR spectroscopy. The results obtained show that these polymeric structures have the capacity to enhance the solubility of ABZ, both lipophilic and specific hydrogen bond interactions contributing to the guest-host association. Although all studied dendrimers have hydrophobic internal nanoenvironments with similar dimensions, their surfaces differ significantly and the nature and the localization of the interactions involved in ABZ-dendrimer association depend on the type of terminal groups.

  10. Solubility improvement of an anthelmintic benzimidazole carbamate by association with dendrimers

    International Nuclear Information System (INIS)

    Fernandez, L.; Sigal, E.; Santo, M.; Otero, L.; Silber, J. J.

    2011-01-01

    The improvement of aqueous solubility of methyl (5-[propylthio]-1H-benzimidazole-2-yl) carbamate, albendazole (ABZ) using polyamidoamine (PAMAM) dendrimers as solubility enhancers was investigated. Full generation PAMAM dendrimers with amine terminal groups, (G3), with hydroxyl terminal groups (G3OH) and half generation PAMAM dendrimers with carboxylate terminal groups (G2.5 and G3.5), were chosen for this study. The nature of dendrimer-ABZ association was investigated by UV absorption, fluorescence emission measurements and by 1 H-NMR spectroscopy. The results obtained show that these polymeric structures have the capacity to enhance the solubility of ABZ, both lipophilic and specific hydrogen bond interactions contributing to the guest-host association. Although all studied dendrimers have hydrophobic internal nanoenvironments with similar dimensions, their surfaces differ significantly and the nature and the localization of the interactions involved in ABZ-dendrimer association depend on the type of terminal groups. (author)

  11. Solubility improvement of an anthelmintic benzimidazole carbamate by association with dendrimers

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez, L.; Sigal, E.; Santo, M., E-mail: msanto@exa.unrc.edu.ar [Departamento de Fisica, Facultad de Ciencias Exactas Fisicoquimicas y Naturales, Universidad Nacional de Rio Cuarto (Argentina); Otero, L.; Silber, J. J. [Departamento de Quimica. Facultad de Ciencias Exactas Fisicoquimicas y Naturales, Universidad Nacional de Rio Cuarto, Rio Cuarto (Argentina)

    2011-10-15

    The improvement of aqueous solubility of methyl (5-[propylthio]-1H-benzimidazole-2-yl) carbamate, albendazole (ABZ) using polyamidoamine (PAMAM) dendrimers as solubility enhancers was investigated. Full generation PAMAM dendrimers with amine terminal groups, (G3), with hydroxyl terminal groups (G3OH) and half generation PAMAM dendrimers with carboxylate terminal groups (G2.5 and G3.5), were chosen for this study. The nature of dendrimer-ABZ association was investigated by UV absorption, fluorescence emission measurements and by {sup 1}H-NMR spectroscopy. The results obtained show that these polymeric structures have the capacity to enhance the solubility of ABZ, both lipophilic and specific hydrogen bond interactions contributing to the guest-host association. Although all studied dendrimers have hydrophobic internal nanoenvironments with similar dimensions, their surfaces differ significantly and the nature and the localization of the interactions involved in ABZ-dendrimer association depend on the type of terminal groups. (author)

  12. Quantitative assessment of surface functionality effects on microglial uptake and retention of PAMAM dendrimers

    Science.gov (United States)

    Liaw, Kevin; Gök, Ozgul; DeRidder, Louis B.; Kannan, Sujatha; Kannan, Rangaramanujam M.

    2018-04-01

    Dendrimers are a promising class of polymeric nanoparticles for delivery of therapeutics and diagnostics. Polyamidoamine (PAMAM) dendrimers have shown significant efficacy in many animal models, with performance dependent on surface functionalities. Understanding the effects of end groups on biological interactions is critical for rational design of dendrimer-mediated therapies. In this study, we quantify the cellular trafficking kinetics (endocytosis and exocytosis) of generation 4 neutral (D4-OH), cationic (D4-NH2), anionic (D3.5-COOH), and generation 6 neutral (D6-OH) PAMAM dendrimers to investigate the nanoscale effects of surface functionality and size on cellular interactions. Resting and LPS-activated microglia were studied due to their central roles in dendrimer therapies for central nervous system disorders. D4-OH exhibits greater cellular uptake and lower retention than the larger D6-OH. D4-OH and D3.5-COOH exhibit similar trafficking kinetics, while D4-NH2 exhibits significant membrane interactions, resulting in faster cell association but lower internalization. Cationic charge may also enhance vesicular escape for greater cellular retention and preferential partitioning to nuclei. LPS activation further improves uptake of dendrimers, with smaller and cationic dendrimers experiencing the greatest increases in uptake compared to resting microglia. These studies have implications for the dependence of trafficking pathway on dendrimer properties and inform the design of dendrimer constructs tailored to specific therapeutic needs. Cationic dendrimers are ideal for delivering genetic materials to nuclei, but toxicity may be a limiting factor. Smaller, neutral dendrimers are best suited for delivering high levels of therapeutics in acute neuroinflammation, while larger or cationic dendrimers provide robust retention for sustained release of therapeutics in longer-term diseases.

  13. Surface, core, and structure modifications of phosphorus-containing dendrimers. Influence on the thermal stability

    OpenAIRE

    Turrin , Cédric-Olivier; Maraval , Valérie; Leclaire , Julien; Dantras , Eric; Lacabanne , Colette; Caminade , Anne-Marie; Majoral , Jean-Pierre

    2003-01-01

    International audience; Three new series of phosphorus-containing dendrimers are described. Their solubility depends on the type of end groups they bear. Perfluoroalkyl chains give dendrimers soluble in chlorofluorocarbons, whereas guanidinium and pyridinium derivatives give watersoluble compounds. The thermal stability of these compounds, as well as of 19 other dendrimers of various generations, having various cores, or various end groups, or branching points is studied. The main feature of ...

  14. Switching the selectivity of a polyglycerol dendrimer monomolecularly imprinted with D-(−)-fructose

    OpenAIRE

    Hashidzume, Akihito; Zimmerman, Steven C.

    2009-01-01

    A polyglycerol dendrimer unimolecularly imprinted with D-(−)-fructose (Fru) was synthesized. The dendrimer formed adducts with several monosaccharides, Fru, D-(+)-galactose, D-(+)-glucose, D-(+)-mannose, and methyl-α-D-mannopyranoside (MMan), by removal of four water molecules. The dendrimer preferred Fru in the absence of N,N,N′,N′-tetramethylmethylenediamine (TMDAM), whereas it preferred MMan in the presence of TMDAM.

  15. Characterization of an engineered cellulose based membrane by thiol dendrimer for heavy metals removal

    OpenAIRE

    Algarra, Manuel; Vázquez, María Isabel; Alonso, Beatriz S.; Casado, Carmen Mª.; Casado, Juan; Benavente, Juana

    2014-01-01

    Diaminobutane based poly(propyleneimine) dendrimer functionalized with sixteen thiol groups, DAB-3-(SH)16, was successfully embeded in a swollen cellulosic support in order to achieve an easily handle engineered membrane. The membrane was characterised by physicochemical, electrical and transport measurements, and the effect of the dendrimer was established by comparing these results with those obtained for the original cellulosic support. Results show that dendrimer inclusion improves the me...

  16. Trapping time statistics and efficiency of transport of optical excitations in dendrimers

    OpenAIRE

    Heijs, D.J.; Malyshev, V.A.; Knoester, J.

    2004-01-01

    We theoretically study the trapping time distribution and the efficiency of the excitation energy transport in dendritic systems. Trapping of excitations, created at the periphery of the dendrimer, on a trap located at its core, is used as a probe of the efficiency of the energy transport across the dendrimer. The transport process is treated as incoherent hopping of excitations between nearest-neighbor dendrimer units and is described using a rate equation. We account for radiative and non-r...

  17. Investigation of original multivalent iminosugars as pharmacological chaperones for the treatment of Gaucher disease.

    Science.gov (United States)

    Laigre, Eugénie; Hazelard, Damien; Casas, Josefina; Serra-Vinardell, Jenny; Michelakakis, Helen; Mavridou, Irene; Aerts, Johannes M F G; Delgado, Antonio; Compain, Philippe

    2016-06-24

    Multivalent iminosugars conjugated with a morpholine moiety and/or designed as prodrugs have been prepared and evaluated as new classes of pharmacological chaperones for the treatment of Gaucher disease. This study further confirms the interest of the prodrug concept and shows that the addition of a lysosome-targeting morpholine unit into iminosugar cluster structures has no significant impact on the chaperone activity on Gaucher cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Synthesis of giant globular multivalent glycofullerenes as potent inhibitors in a model of Ebola virus infection

    Science.gov (United States)

    Muñoz, Antonio; Sigwalt, David; Illescas, Beatriz M.; Luczkowiak, Joanna; Rodríguez-Pérez, Laura; Nierengarten, Iwona; Holler, Michel; Remy, Jean-Serge; Buffet, Kevin; Vincent, Stéphane P.; Rojo, Javier; Delgado, Rafael; Nierengarten, Jean-François; Martín, Nazario

    2016-01-01

    The use of multivalent carbohydrate compounds to block cell-surface lectin receptors is a promising strategy to inhibit the entry of pathogens into cells and could lead to the discovery of novel antiviral agents. One of the main problems with this approach, however, is that it is difficult to make compounds of an adequate size and multivalency to mimic natural systems such as viruses. Hexakis adducts of [60]fullerene are useful building blocks in this regard because they maintain a globular shape at the same time as allowing control over the size and multivalency. Here we report water-soluble tridecafullerenes decorated with 120 peripheral carbohydrate subunits, so-called ‘superballs’, that can be synthesized efficiently from hexakis adducts of [60]fullerene in one step by using copper-catalysed azide-alkyne cycloaddition click chemistry. Infection assays show that these superballs are potent inhibitors of cell infection by an artificial Ebola virus with half-maximum inhibitory concentrations in the subnanomolar range.

  19. Poly(amidoamine) (PAMAM) dendrimers: from biomimicry to drug delivery and biomedical applications.

    Science.gov (United States)

    Esfand, R; Tomalia, D A.

    2001-04-01

    Poly(amidoamine) (PAMAM) dendrimers are the first complete dendrimer family to be synthesized, characterized and commercialized. Based on this extensive activity, they are recognized as a unique new class of synthetic nanostructures. Dendrimers allow the precise control of size, shape and placement of functional groups that is desirable for many life science applications. From this perspective, this review focuses on crucial properties of biomimetic dendrimers that will broaden the potential for their use as macromolecular vectors in novel drug delivery and biomedical applications.

  20. Magnetic properties of dendrimer structures with different coordination numbers: A Monte Carlo study

    International Nuclear Information System (INIS)

    Masrour, R.; Jabar, A.

    2016-01-01

    We investigate the magnetic properties of Cayley trees of large molecules with dendrimer structure using Monte Carlo simulations. The thermal magnetization and magnetic susceptibility of a dendrimer structure are given with different coordination numbers, Z=3, 4, 5 and different generations g=3 and 2. The variation of magnetizations with the exchange interactions and crystal fields have been given of this system. The magnetic hysteresis cycles have been established. - Highlights: • The dendrimer structure is investigated using Monte Carlo simulations. • The transition temperatures are obtained for different coordination numbers and generations. • The magnetic hysteresis cycle has been established. • The dendrimer structure exhibit the superparamagnetic behavior.

  1. Effect of solvent-controlled aggregation on the intrinsic emission properties of PAMAM dendrimers

    International Nuclear Information System (INIS)

    Jasmine, Maria J.; Kavitha, Manniledam; Prasad, Edamana

    2009-01-01

    Solvent-induced aggregation and its effect on the intrinsic emission properties of amine, hydroxy and carboxylate terminated, poly(amidoamine) (PAMAM) dendrimers have been investigated in glycerol, ethylene glycol, methanol, ethylene diamine and water. Altering the solvent medium induces remarkable changes in the intrinsic emission properties of the PAMAM dendrimers at identical concentration. Upon excitation at 370 nm, amine terminated PAMAM dendrimer exhibits an intense emission at 470 nm in glycerol, ethylene glycol as well as glycerol-water mixtures. Conversely, weak luminescence is observed for hydroxy and carboxylate terminated PAMAM dendrimers in the same solvent systems. When the solvent is changed to ethylene diamine, hydroxy terminated PAMAM exhibits intense blue emission at 425 nm. While the emission intensity is varied when the solvent milieu is changed, excited state lifetime values of PAMAM dendrimers remain independent of the solvent used. UV-visible absorption and dynamic light scattering (DLS) experiments confirm the formation of solvent-controlled dendrimer aggregates in the systems. Comparison of the fluorescence and DLS data reveals that the size distribution of the dendrimer aggregates in each solvent system is distinct, which control the intrinsic emission intensity from PAMAM dendrimers. The experimental results suggest that intrinsic emission intensity from PAMAM dendrimers can be regulated by proper selection of solvents at neutral conditions and room temperature

  2. Oligodeoxynucleotide nanostructure formation in the presence of polypropyleneimine dendrimers and their uptake in breast cancer cells

    International Nuclear Information System (INIS)

    Chen, Alex M; Santhakumaran, Latha M; Nair, Sandhya K; Amenta, Peter S; Thomas, Thresia; He, Huixin; Thomas, T J

    2006-01-01

    We studied the efficacy of five generations of polypropyleneimine (PPI) dendrimer to provoke nanostructure formation from a 21-nucleotide antisense oligodeoxynucleotide (ODN). Nanostructure formation was observed with all generations of dendrimer by light scattering and microscopic techniques. The efficacy of the dendrimers increased with generation number. Atomic force microscopy (AFM) was used to study the morphology of the structures at different condensation stages. Based on the observed nanostructures, we propose a zipping condensation mechanism, which is very different from the condensation pathways of high molecular weight DNA polymers. Electron microscopy showed the presence of toroidal nanoparticles. Confocal microscopic analysis showed that the nanostructures formed with G-4 and G-5 dendrimers could undergo facile cellular uptake in a breast cancer cell line, MDA-MB-231, whereas nanostructures formed with G-1 to G-3 dendrimers lacked this ability. Nanoparticles formed with G-1 to G-3 dendrimers showed significantly lower zeta potential (5.2-6.5 mV) than those (12-18 mV) of particles formed with G-4 and G-5 dendrimers. These results show that the structure and charge density of the dendrimers are important in ODN nanoparticle formation and cellular transport and that G-4 and G-5 dendrimers are useful in cellular delivery of antisense ODN

  3. Synthesis of Polyamidoamine Dendrimer for Encapsulating Tetramethylscutellarein for Potential Bioactivity Enhancement.

    Science.gov (United States)

    Shadrack, Daniel M; Mubofu, Egid B; Nyandoro, Stephen S

    2015-11-04

    The biomedical potential of flavonoids is normally restricted by their low water solubility. However, little has been reported on their encapsulation into polyamidoamine (PAMAM) dendrimers to improve their biomedical applications. Generation four (G4) PAMAM dendrimer containing ethylenediaminetetraacetic acid core with acrylic acid and ethylenediamine as repeating units was synthesized by divergent approach and used to encapsulate a flavonoid tetramethylscutellarein (TMScu, 1) to study its solubility and in vitro release for potential bioactivity enhancement. The as-synthesized dendrimer and the dendrimer-TMScu complex were characterized by spectroscopic and spectrometric techniques. The encapsulation of 1 into dendrimer was achieved by a co-precipitation method with the encapsulation efficiency of 77.8% ± 0.69% and a loading capacity of 6.2% ± 0.06%. A phase solubility diagram indicated an increased water solubility of 1 as a function of dendrimer concentration at pH 4.0 and 7.2. In vitro release of 1 from its dendrimer complex indicated high percentage release at pH 4.0. The stability study of the TMScu-dendrimer at 0, 27 and 40 °C showed the formulations to be stable when stored in cool and dark conditions compared to those stored in light and warmer temperatures. Overall, PAMAM dendrimer-G4 is capable of encapsulating 1, increasing its solubility and thus could enhance its bioactivity.

  4. Optimization of dendrimer structure for sentinel lymph node imaging: Effects of generation and terminal group.

    Science.gov (United States)

    Niki, Yuichiro; Ogawa, Mikako; Makiura, Rie; Magata, Yasuhiro; Kojima, Chie

    2015-11-01

    The detection of the sentinel lymph node (SLN), the first lymph node draining tumor cells, is important in cancer diagnosis and therapy. Dendrimers are synthetic macromolecules with highly controllable structures, and are potent multifunctional imaging agents. In this study, 12 types of dendrimer of different generations (G2, G4, G6, and G8) and different terminal groups (amino, carboxyl, and acetyl) were prepared to determine the optimal dendrimer structure for SLN imaging. Radiolabeled dendrimers were intradermally administrated to the right footpads of rats. All G2 dendrimers were predominantly accumulated in the kidney. Amino-terminal, acetyl-terminal, and carboxyl-terminal dendrimers of greater than G4 were mostly located at the injection site, in the blood, and in the SLN, respectively. The carboxyl-terminal dendrimers were largely unrecognized by macrophages and T-cells in the SLN. Finally, SLN detection was successfully performed by single photon emission computed tomography imaging using carboxyl-terminal dendrimers of greater than G4. The early detection of tumor cells in the sentinel draining lymph nodes (SLN) is of utmost importance in terms of determining cancer prognosis and devising treatment. In this article, the authors investigated various formulations of dendrimers to determine the optimal one for tumor detection. The data generated from this study would help clinicians to fight the cancer battle in the near future. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Magnetic properties of dendrimer structures with different coordination numbers: A Monte Carlo study

    Energy Technology Data Exchange (ETDEWEB)

    Masrour, R., E-mail: rachidmasrour@hotmail.com; Jabar, A.

    2016-11-01

    We investigate the magnetic properties of Cayley trees of large molecules with dendrimer structure using Monte Carlo simulations. The thermal magnetization and magnetic susceptibility of a dendrimer structure are given with different coordination numbers, Z=3, 4, 5 and different generations g=3 and 2. The variation of magnetizations with the exchange interactions and crystal fields have been given of this system. The magnetic hysteresis cycles have been established. - Highlights: • The dendrimer structure is investigated using Monte Carlo simulations. • The transition temperatures are obtained for different coordination numbers and generations. • The magnetic hysteresis cycle has been established. • The dendrimer structure exhibit the superparamagnetic behavior.

  6. Oligodeoxynucleotide nanostructure formation in the presence of polypropyleneimine dendrimers and their uptake in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Alex M [Department of Chemistry, Rutgers University, 73 Warren Street, Newark, NJ 07102 (United States); Santhakumaran, Latha M [Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08903 (United States); Nair, Sandhya K [Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08903 (United States); Amenta, Peter S [Department of Pathology and Laboratory Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08903 (United States); Thomas, Thresia [Department of Environmental and Health Sciences Institute, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08903 (United States); He, Huixin [Department of Chemistry, Rutgers University, 73 Warren Street, Newark, NJ 07102 (United States); Thomas, T J [Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08903 (United States)

    2006-11-14

    We studied the efficacy of five generations of polypropyleneimine (PPI) dendrimer to provoke nanostructure formation from a 21-nucleotide antisense oligodeoxynucleotide (ODN). Nanostructure formation was observed with all generations of dendrimer by light scattering and microscopic techniques. The efficacy of the dendrimers increased with generation number. Atomic force microscopy (AFM) was used to study the morphology of the structures at different condensation stages. Based on the observed nanostructures, we propose a zipping condensation mechanism, which is very different from the condensation pathways of high molecular weight DNA polymers. Electron microscopy showed the presence of toroidal nanoparticles. Confocal microscopic analysis showed that the nanostructures formed with G-4 and G-5 dendrimers could undergo facile cellular uptake in a breast cancer cell line, MDA-MB-231, whereas nanostructures formed with G-1 to G-3 dendrimers lacked this ability. Nanoparticles formed with G-1 to G-3 dendrimers showed significantly lower zeta potential (5.2-6.5 mV) than those (12-18 mV) of particles formed with G-4 and G-5 dendrimers. These results show that the structure and charge density of the dendrimers are important in ODN nanoparticle formation and cellular transport and that G-4 and G-5 dendrimers are useful in cellular delivery of antisense ODN.

  7. Transepithelial transport and toxicity of PAMAM dendrimers: implications for oral drug delivery.

    Science.gov (United States)

    Sadekar, S; Ghandehari, H

    2012-05-01

    This article summarizes efforts to evaluate poly(amido amine) (PAMAM) dendrimers as carriers for oral drug delivery. Specifically, the effect of PAMAM generation, surface charge and surface modification on toxicity, cellular uptake and transepithelial transport is discussed. Studies on Caco-2 monolayers, as models of intestinal epithelial barrier, show that by engineering surface chemistry of PAMAM dendrimers, it is possible to minimize toxicity while maximizing transepithelial transport. It has been demonstrated that PAMAM dendrimers are transported by a combination of paracellular and transcellular routes. Depending on surface chemistry, PAMAM dendrimers can open the tight junctions of epithelial barriers. This tight junction opening is in part mediated by internalization of the dendrimers. Transcellular transport of PAMAM dendrimers is mediated by a variety of endocytic mechanisms. Attachment or complexation of cytotoxic agents to PAMAM dendrimers enhances the transport of such drugs across epithelial barriers. A remaining challenge is the design and development of linker chemistries that are stable in the gastrointestinal tract (GIT) and the blood stream, but amenable to cleavage at the target site of action. Recent efforts have focused on the use of PAMAM dendrimers as penetration enhancers. Detailed in vivo oral bioavailability of PAMAM dendrimer-drug conjugates, as a function of physicochemical properties will further need to be assessed. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Oligodeoxynucleotide nanostructure formation in the presence of polypropyleneimine dendrimers and their uptake in breast cancer cells

    Science.gov (United States)

    Chen, Alex M.; Santhakumaran, Latha M.; Nair, Sandhya K.; Amenta, Peter S.; Thomas, Thresia; He, Huixin; Thomas, T. J.

    2006-11-01

    We studied the efficacy of five generations of polypropyleneimine (PPI) dendrimer to provoke nanostructure formation from a 21-nucleotide antisense oligodeoxynucleotide (ODN). Nanostructure formation was observed with all generations of dendrimer by light scattering and microscopic techniques. The efficacy of the dendrimers increased with generation number. Atomic force microscopy (AFM) was used to study the morphology of the structures at different condensation stages. Based on the observed nanostructures, we propose a zipping condensation mechanism, which is very different from the condensation pathways of high molecular weight DNA polymers. Electron microscopy showed the presence of toroidal nanoparticles. Confocal microscopic analysis showed that the nanostructures formed with G-4 and G-5 dendrimers could undergo facile cellular uptake in a breast cancer cell line, MDA-MB-231, whereas nanostructures formed with G-1 to G-3 dendrimers lacked this ability. Nanoparticles formed with G-1 to G-3 dendrimers showed significantly lower zeta potential (5.2-6.5 mV) than those (12-18 mV) of particles formed with G-4 and G-5 dendrimers. These results show that the structure and charge density of the dendrimers are important in ODN nanoparticle formation and cellular transport and that G-4 and G-5 dendrimers are useful in cellular delivery of antisense ODN.

  9. Homogeneous alignment of liquid crystalline dendrimers confined in a slit-pore. A simulation study.

    Science.gov (United States)

    Workineh, Zerihun G; Vanakaras, Alexandros G

    2016-03-23

    In this work we present results from isobaric-isothermal (NPT) Monte Carlo simulation studies of model liquid crystalline dendrimer (LCDr) systems confined in a slit-pore made of two parallel flat walls. The dendrimers are modelled as a collection of spherical and ellipsoidal particles corresponding to the junction points of the dendritic core and to the mesogenic units respectively. Assuming planar uniform (unidirectional) soft anchoring of the mesogenic units on the substrates we investigate the conformational and alignment properties of the LCDr system at different thermodynamic state points. Tractable coarse grained force fields have been used from our previous work. At low pressures the interior of the pore is almost empty, since almost all LCDrs are anchored to the substrates forming two-dimensional smectic-like structures with the mesogens aligned along the aligning direction of the substrates. As the pressure grows the LCDrs occupy the whole pore. However, even at low temperatures, the smectic organization does not transmit in the interior of the pore and is preserved for distances of 2-3 mesogenic diameters from the walls. For this reason, the global orientational order decreases with increasing pressure (density). In the vicinity (2-3 mesogenic diameters) of the pore walls, mesogenic units preserve the smectic structure whose layers are separated by layers of spherical beads. In this region individual LCDrs possess a rod like shape.

  10. Oriented Polyaniline Nanowire Arrays Grown on Dendrimer (PAMAM) Functionalized Multiwalled Carbon Nanotubes as Supercapacitor Electrode Materials.

    Science.gov (United States)

    Jin, Lin; Jiang, Yu; Zhang, Mengjie; Li, Honglong; Xiao, Linghan; Li, Ming; Ao, Yuhui

    2018-04-19

    At present, PANI/MWNT composites have been paid more attention as promising electrode materials in supercapacitors. Yet some shortcomings still limit the widely application of PANI/MWNT electrolytes. In this work, in order to improve capacitance ability and long-term stability of electrode, a multi-amino dendrimer (PAMAM) had been covalently linked onto multi-walled carbon nanotubes (MWNT) as a bridge to facilitating covalent graft of polyaniline (PANI), affording P-MWNT/PANI electrode composites for supercapacitor. Surprisingly, ordered arrays of PANI nanowires on MWNT (setaria-like morphology) had been observed by scanning electron microscopy (SEM). Electrochemical properties of P-MWNT/PANI electrode had been characterized by cyclic voltammetry (CV) and galvanostatic charge-discharge technique. The specific capacitance and long cycle life of P-MWNT-PANI electrode material were both much higher than MWNT/PANI. These interesting results indicate that multi-amino dendrimer, PAMAM, covalently linked on MWNT provides more reaction sites for in-situ polymerization of ordered PANI, which could efficiently shorten the ion diffusion length in electrolytes and lead to making fully use of conducting materials.

  11. Homogeneous alignment of liquid crystalline dendrimers confined in a slit-pore. A simulation study

    Science.gov (United States)

    Workineh, Zerihun G.; Vanakaras, Alexandros G.

    2016-03-01

    In this work we present results from isobaric-isothermal (NPT) Monte Carlo simulation studies of model liquid crystalline dendrimer (LCDr) systems confined in a slit-pore made of two parallel flat walls. The dendrimers are modelled as a collection of spherical and ellipsoidal particles corresponding to the junction points of the dendritic core and to the mesogenic units respectively. Assuming planar uniform (unidirectional) soft anchoring of the mesogenic units on the substrates we investigate the conformational and alignment properties of the LCDr system at different thermodynamic state points. Tractable coarse grained force fields have been used from our previous work. At low pressures the interior of the pore is almost empty, since almost all LCDrs are anchored to the substrates forming two-dimensional smectic-like structures with the mesogens aligned along the aligning direction of the substrates. As the pressure grows the LCDrs occupy the whole pore. However, even at low temperatures, the smectic organization does not transmit in the interior of the pore and is preserved for distances of 2-3 mesogenic diameters from the walls. For this reason, the global orientational order decreases with increasing pressure (density). In the vicinity (2-3 mesogenic diameters) of the pore walls, mesogenic units preserve the smectic structure whose layers are separated by layers of spherical beads. In this region individual LCDrs possess a rod like shape.

  12. Homogeneous alignment of liquid crystalline dendrimers confined in a slit-pore. A simulation study

    International Nuclear Information System (INIS)

    Workineh, Zerihun G; Vanakaras, Alexandros G

    2016-01-01

    In this work we present results from isobaric-isothermal (NPT) Monte Carlo simulation studies of model liquid crystalline dendrimer (LCDr) systems confined in a slit-pore made of two parallel flat walls. The dendrimers are modelled as a collection of spherical and ellipsoidal particles corresponding to the junction points of the dendritic core and to the mesogenic units respectively. Assuming planar uniform (unidirectional) soft anchoring of the mesogenic units on the substrates we investigate the conformational and alignment properties of the LCDr system at different thermodynamic state points. Tractable coarse grained force fields have been used from our previous work. At low pressures the interior of the pore is almost empty, since almost all LCDrs are anchored to the substrates forming two-dimensional smectic-like structures with the mesogens aligned along the aligning direction of the substrates. As the pressure grows the LCDrs occupy the whole pore. However, even at low temperatures, the smectic organization does not transmit in the interior of the pore and is preserved for distances of 2–3 mesogenic diameters from the walls. For this reason, the global orientational order decreases with increasing pressure (density). In the vicinity (2–3 mesogenic diameters) of the pore walls, mesogenic units preserve the smectic structure whose layers are separated by layers of spherical beads. In this region individual LCDrs possess a rod like shape. (paper)

  13. Poly(amido)amine (PAMAM) dendrimer-cisplatin complexes for chemotherapy of cisplatin-resistant ovarian cancer cells

    Science.gov (United States)

    Yellepeddi, Venkata Kashyap; Vangara, Kiran Kumar; Palakurthi, Srinath

    2013-09-01

    Dendrimer-cisplatin complexes were prepared using PAMAM dendrimers with terminal -NH2 and -COOH groups as well as biotin-conjugated dendrimers. Preformulation parameters of dendrimer-cisplatin complexes were studied using differential scanning calorimetry (DSC) and inductively coupled plasma-mass spectrometry (ICP-MS). Cytotoxicity and mechanism of cytotoxicity of dendrimer-cisplatin complexes was investigated in OVCAR-3, SKOV, A2780 and cisplatin-resistant CP70 human ovarian cancer cell lines. The loading of cisplatin in dendrimers was 11 % (w/w). PAMAM G4 dendrimers with amine surface groups (biotinylated and native) have shown 2.5- to 3.0-fold reduction in IC50 values in ovarian cancer cells when compared with carboxylate surface dendrimers ( p cisplatin complexes resulted in a 7.0-fold increase ( p cisplatin chemotherapy of ovarian cancer.

  14. Methotrexate loaded polyether-copolyester dendrimers for the treatment of gliomas: enhanced efficacy and intratumoral transport capability.

    Science.gov (United States)

    Dhanikula, Renu Singh; Argaw, Anteneh; Bouchard, Jean-Francois; Hildgen, Patrice

    2008-01-01

    Therapeutic benefit in glial tumors is often limited due to low permeability of delivery systems across the blood-brain barrier (BBB), drug resistance, and poor penetration into the tumor tissue. In an attempt to overcome these hurdles, polyether-copolyester (PEPE) dendrimers were evaluated as drug carriers for the treatment of gliomas. Dendrimers were conjugated to d-glucosamine as the ligand for enhancing BBB permeability and tumor targeting. The efficacy of methotrexate (MTX)-loaded dendrimers was established against U87 MG and U 343 MGa cells. Permeability of rhodamine-labeled dendrimers and MTX-loaded dendrimers across the in vitro BBB model and their distribution into avascular human glioma tumor spheroids was also studied. Glucosylated dendrimers were found to be endocytosed in significantly higher amounts than nonglucosylated dendrimers by both the cell lines. IC 50 of MTX after loading in dendrimers was lower than that of the free MTX, suggesting that loading MTX in PEPE dendrimers increased its potency. Similar higher activity of MTX-loaded glucosylated and nonglucosylated dendrimers was found in the reduction of tumor spheroid size. These MTX-loaded dendrimers were able to kill even MTX-resistant cells highlighting their ability to overcome MTX resistance. In addition, the amount of MTX-transported across BBB was three to five times more after loading in the dendrimers. Glucosylation further increased the cumulative permeation of dendrimers across BBB and hence increased the amount of MTX available across it. Glucosylated dendrimers distributed through out the avascular tumor spheroids within 6 h, while nonglucosylated dendrimers could do so in 12 h. The results show that glucosamine can be used as an effective ligand not only for targeting glial tumors but also for enhanced permeability across BBB. Thus, glucosylated PEPE dendrimers can serve as potential delivery system for the treatment of gliomas.

  15. Transcorneal iontophoresis of dendrimers: PAMAM corneal penetration and dexamethasone delivery.

    Science.gov (United States)

    Souza, Joel G; Dias, Karina; Silva, Silas A M; de Rezende, Lucas C D; Rocha, Eduardo M; Emery, Flavio S; Lopez, Renata F V

    2015-02-28

    Iontophoresis of nanocarriers in the eye has been proposed to sustain drug delivery and maintain therapeutic concentrations. Fourth generation polyamidoamine (PAMAM) dendrimers are semi-rigid nanoparticles with surface groups that are easily modified. These dendrimers are known to modulate tight junctions, increase paracellular transport of small molecules and be translocated across epithelial barriers, exhibiting high uptake by different cell lines. The first aim of this study was to investigate the effect of iontophoresis on PAMAM penetration and distribution into the cornea. The second aim was to evaluate, ex vivo and in vivo, the effect of these dendrimers in dexamethasone (Dex) transcorneal iontophoresis. Anionic (PAMAM G3.5) and cationic (PAMAM G4) dendrimers were labeled with fluorescein isothiocyanate (FITC), and their distribution in the cornea was investigated using confocal microscopy after ex vivo anodal and cathodal iontophoresis for various application times. The particle size distribution and zeta potential of the dendrimers in an isosmotic solution were determined using dynamic light scattering and Nanoparticle Tracking Analysis (NTA), where the movement of small particles and the formation of large aggregates, from 5 to 100 nm, could be observed. Transcorneal iontophoresis increased the intensity and depth of PAMAM-FITC fluorescence in the cornea, suggesting improved transport of the dendrimers across the epithelium toward the stroma. PAMAM complexes with Dex were characterized by (13)C-NMR, (1)H-NMR and DOSY. PAMAM G3.5 and PAMAM G4 increased the aqueous solubility of Dex by 10.3 and 3.9-fold, respectively; however, the particle size distribution and zeta potential remained unchanged. PAMAM G3.5 decreased the Dex diffusion coefficient 48-fold compared with PAMAM G4. The ex vivo studies showed that iontophoresis increased the amount of Dex that penetrated into the cornea by 2.9, 5.6 and 3.0-fold for Dex, Dex-PAMAM G4 and Dex-PAMAM G3

  16. In Silico Characterization of the Binding Affinity of Dendrimers to Penicillin-Binding Proteins (PBPs): Can PBPs be Potential Targets for Antibacterial Dendrimers?

    Science.gov (United States)

    Ahmed, Shaimaa; Vepuri, Suresh B; Ramesh, Muthusamy; Kalhapure, Rahul; Suleman, Nadia; Govender, Thirumala

    2016-04-01

    We have shown that novel silver salts of poly (propyl ether) imine (PETIM) dendron and dendrimers developed in our group exhibit preferential antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus. This led us to examine whether molecular modeling methods could be used to identify the key structural design principles for a bioactive lead molecule, explore the mechanism of binding with biological targets, and explain their preferential antibacterial activity. The current article reports the conformational landscape as well as mechanism of binding of generation 1 PETIM dendron and dendrimers to penicillin-binding proteins (PBPs) in order to understand the antibacterial activity profiles of their silver salts. Molecular dynamics at different simulation protocols and conformational analysis were performed to elaborate on the conformational features of the studied dendrimers, as well as to create the initial structure for further binding studies. The results showed that for all compounds, there were no significant conformational changes due to variation in simulation conditions. Molecular docking calculations were performed to investigate the binding theme between the studied dendrimers and PBPs. Interestingly, in significant accordance with the experimental data, dendron and dendrimer with aliphatic cores were found to show higher activity against S. aureus than the dendrimer with an aromatic core. The latter showed higher activity against MRSA. The findings from this computational and molecular modeling report together with the experimental results serve as a road map toward designing more potent antibacterial dendrimers against resistant bacterial strains.

  17. Immunologic properties and therapeutic efficacy of a multivalent epitope-based vaccine against four Helicobacter pylori adhesins (urease, Lpp20, HpaA, and CagL) in Mongolian gerbils.

    Science.gov (United States)

    Guo, Le; Yin, Runting; Xu, Guangxian; Gong, Xiaojuan; Chang, Zisong; Hong, Dantong; Liu, Hongpeng; Ding, Shuqin; Han, Xuebo; Li, Yuan; Tang, Feng; Liu, Kunmei

    2017-12-01

    Therapeutic vaccination is a desirable alternative for controlling Helicobacter pylori (H. pylori) infection. Attachment to the gastric mucosa is the first step in establishing bacterial colonization, and adhesins, which are on the surface of H. pylori, play a pivotal role in binding to human gastric mucosa. In the present study, we constructed a multivalent epitope-based vaccine named CFAdE with seven carefully selected antigenic fragments from four H. pylori adhesins (urease, Lpp20, HpaA and CagL). The specificity, immunogenicity and ability to produce neutralizing antibodies of CFAdE were evaluated in BALB/c mice. After that, its therapeutic efficacy and protective immune mechanisms were explored in H. pylori-infected Mongolian gerbils. The results indicated that CFAdE could induce comparatively high levels of specific antibodies against urease, Lpp20, HpaA and CagL. Additionally, oral therapeutic immunization with CFAdE plus polysaccharide adjuvant (PA) significantly decreased H. pylori colonization compared with oral immunization with urease plus PA, and the protection was correlated with IgG and sIgA antibody and antigen-specific CD4 + T cells. This study indicated that the multivalent epitope-based vaccine, which targeted multiple adhesins in adherence of H. pylori to the gastric mucosa, is more effective than the univalent vaccine targeting urease only. This multivalent epitope-based vaccine may be a promising therapeutic candidate vaccine against H. pylori infection. © 2017 John Wiley & Sons Ltd.

  18. RGD peptide-modified multifunctional dendrimer platform for drug encapsulation and targeted inhibition of cancer cells.

    Science.gov (United States)

    He, Xuedan; Alves, Carla S; Oliveira, Nilsa; Rodrigues, João; Zhu, Jingyi; Bányai, István; Tomás, Helena; Shi, Xiangyang

    2015-01-01

    Development of multifunctional nanoscale drug-delivery systems for targeted cancer therapy still remains a great challenge. Here, we report the synthesis of cyclic arginine-glycine-aspartic acid (RGD) peptide-conjugated generation 5 (G5) poly(amidoamine) dendrimers for anticancer drug encapsulation and targeted therapy of cancer cells overexpressing αvβ3 integrins. In this study, amine-terminated G5 dendrimers were used as a platform to be sequentially modified with fluorescein isothiocyanate (FI) via a thiourea linkage and RGD peptide via a polyethylene glycol (PEG) spacer, followed by acetylation of the remaining dendrimer terminal amines. The developed multifunctional dendrimer platform (G5.NHAc-FI-PEG-RGD) was then used to encapsulate an anticancer drug doxorubicin (DOX). We show that approximately six DOX molecules are able to be encapsulated within each dendrimer platform. The formed complexes are water-soluble, stable, and able to release DOX in a sustained manner. One- and two-dimensional NMR techniques were applied to investigate the interaction between dendrimers and DOX, and the impact of the environmental pH on the release rate of DOX from the dendrimer/DOX complexes was also explored. Furthermore, cell biological studies demonstrate that the encapsulation of DOX within the G5.NHAc-FI-PEG-RGD dendrimers does not compromise the anticancer activity of DOX and that the therapeutic efficacy of the dendrimer/DOX complexes is solely related to the encapsulated DOX drug. Importantly, thanks to the role played by RGD-mediated targeting, the developed dendrimer/drug complexes are able to specifically target αvβ3 integrin-overexpressing cancer cells and display specific therapeutic efficacy to the target cells. The developed RGD peptide-targeted multifunctional dendrimers may thus be used as a versatile platform for targeted therapy of different types of αvβ3 integrin-overexpressing cancer cells. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Lactose-containing starburst dendrimers: influence of dendrimer generation and binding-site orientation of receptors (plant/animal lectins and immunoglobulins) on binding properties.

    Science.gov (United States)

    André, S; Ortega, P J; Perez, M A; Roy, R; Gabius, H J

    1999-11-01

    Starburst glycodendrimers offer the potential to serve as high-affinity ligands for clinically relevant sugar receptors. In order to define areas of application, their binding behavior towards sugar receptors with differential binding-site orientation but identical monosaccharide specificity must be evaluated. Using poly(amidoamine) starburst dendrimers of five generations, which contain the p-isothiocyanato derivative of p-aminophenyl-beta-D-lactoside as ligand group, four different types of galactoside-binding proteins were chosen for this purpose, i.e., the (AB)(2)-toxic agglutinin from mistletoe, a human immunoglobulin G fraction, the homodimeric galectin-1 with its two binding sites at opposite ends of the jelly-roll-motif-harboring protein and monomeric galectin-3. Direct solid-phase assays with surface-immobilized glycodendrimers resulted in obvious affinity enhancements by progressive core branching for the plant agglutinin and less pronounced for the antibody and galectin-1. High density of binding of galectin-3 with modest affinity increases only from the level of the 32-mer onwards points to favorable protein-protein interactions of the monomeric lectin and a spherical display of the end groups without a major share of backfolding. When the inhibitory potency of these probes was evaluated as competitor of receptor binding to an immobilized neoglycoprotein or to asialofetuin, a marked selectivity was detected. The 32- and 64-mers were second to none as inhibitors for the plant agglutinin against both ligand-exposing matrices and for galectin-1 on the matrix with a heterogeneous array of interglycoside distances even on the per-sugar basis. In contrast, a neoglycoprotein with the same end group was superior in the case of the antibody and, less pronounced, monomeric galectin-3. Intimate details of topological binding-site presentation and the ligand display on different generations of core assembly are major operative factors which determine the potential

  20. Photoinduced electron transfer between benzyloxy dendrimer phthalocyanine and benzoquinone

    Science.gov (United States)

    Zhang, Tiantian; Ma, Dongdong; Pan, Sujuan; Wu, Shijun; Jiang, Yufeng; Zeng, Di; Yang, Hongqin; Peng, Yiru

    2016-10-01

    Photo-induced electron transfer (PET) is an important and fundamental process in natural photosynthesis. To mimic such interesting PET process, a suitable donor and acceptor couple were properly chosen. Dendrimer phthalocyanines and their derivatives have emerged as promising materials for artificial photosynthesis systems. In this paper, the electron transfer between the light harvest dendrimer phthalocyanine (donor) and the 1,4-benzoquinone (acceptor) was studied by UV/Vis and fluorescence spectroscopic methods. It was found that fluorescence of phthalocyanine was quenched by benzoquinone (BQ) via excited state electron transfer, from the phthalocyanine to the BQ upon excitation at 610 nm. The Stern-Volmer constant (KSV) of electron transfer was calculated. Our study suggests that this dendritic phthalocyanine is an effective new electron donor and transmission complex and could be used as a potential artificial photosynthesis system.

  1. Current-voltage characteristics of dendrimer light-emitting diodes

    International Nuclear Information System (INIS)

    Stevenson, S G; Samuel, I D W; Staton, S V; Knights, K A; Burn, P L; Williams, J H T; Walker, Alison B

    2010-01-01

    We have investigated current-voltage (I-V) characteristics of unipolar and bipolar organic diodes that use phosphorescent dendrimers as the emissive organic layer. Through simulation of the measured I-V characteristics we were able to determine the device parameters for each device structure studied, leading to a better understanding of injection and transport behaviour in these devices. It was found that the common practice of assuming injection barriers are equal to the difference between bare electrode work functions and molecular orbital levels is unsuitable for the devices considered here, particularly for gold contacts. The studies confirm that different aromatic units in the dendrons can give significant differences in the charge transporting properties of the dendrimers.

  2. Current-voltage characteristics of dendrimer light-emitting diodes

    Science.gov (United States)

    Stevenson, S. G.; Samuel, I. D. W.; Staton, S. V.; Knights, K. A.; Burn, P. L.; Williams, J. H. T.; Walker, Alison B.

    2010-09-01

    We have investigated current-voltage (I-V) characteristics of unipolar and bipolar organic diodes that use phosphorescent dendrimers as the emissive organic layer. Through simulation of the measured I-V characteristics we were able to determine the device parameters for each device structure studied, leading to a better understanding of injection and transport behaviour in these devices. It was found that the common practice of assuming injection barriers are equal to the difference between bare electrode work functions and molecular orbital levels is unsuitable for the devices considered here, particularly for gold contacts. The studies confirm that different aromatic units in the dendrons can give significant differences in the charge transporting properties of the dendrimers.

  3. Current-voltage characteristics of dendrimer light-emitting diodes

    Energy Technology Data Exchange (ETDEWEB)

    Stevenson, S G; Samuel, I D W [Organic Semiconductor Centre, SUPA, School of Physics and Astronomy, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9SS (United Kingdom); Staton, S V; Knights, K A; Burn, P L [Department of Chemistry, Chemistry Research Laboratory, 12 Mansfield Road, Oxford, OX1 3TA (United Kingdom); Williams, J H T; Walker, Alison B, E-mail: a.b.walker@bath.ac.u [Department of Physics, University of Bath, Bath, BA2 7AY (United Kingdom)

    2010-09-29

    We have investigated current-voltage (I-V) characteristics of unipolar and bipolar organic diodes that use phosphorescent dendrimers as the emissive organic layer. Through simulation of the measured I-V characteristics we were able to determine the device parameters for each device structure studied, leading to a better understanding of injection and transport behaviour in these devices. It was found that the common practice of assuming injection barriers are equal to the difference between bare electrode work functions and molecular orbital levels is unsuitable for the devices considered here, particularly for gold contacts. The studies confirm that different aromatic units in the dendrons can give significant differences in the charge transporting properties of the dendrimers.

  4. Wiring of heme enzymes by methylene-blue labeled dendrimers

    DEFF Research Database (Denmark)

    Álvarez-Martos, Isabel; Shahdost-fard, Faezeh; Ferapontova, Elena

    2017-01-01

    Redox-modified branched 3D dendrimeric nanostructures may be considered as perspective wires for electrical connection between redox enzymes and electrodes. Here, we studied electron transfer (ET) reactions and bioelectrocatalysis of heme-containing horseradish peroxidase (HRP) and heme- and moli......Redox-modified branched 3D dendrimeric nanostructures may be considered as perspective wires for electrical connection between redox enzymes and electrodes. Here, we studied electron transfer (ET) reactions and bioelectrocatalysis of heme-containing horseradish peroxidase (HRP) and heme......- and molibdopterin-containing sulfite oxidase (SOx), wired to gold by the methylene blue (MB)-labeled polyamidoamine (PAMAM) dendrimers. The enzymes’ electrochemical transformation and bioelectrocatalytic function could be followed at both unlabeled and MB-labeled dendrimer-modified electrodes with the formal redox......, optimization of bioelectrocatalysis of complex intermembrane and, possibly, membrane enzymes....

  5. Biological properties of new viologen-phosphorus dendrimers.

    Science.gov (United States)

    Ciepluch, Karol; Katir, Nadia; El Kadib, Abdelkrim; Felczak, Aleksandra; Zawadzka, Katarzyna; Weber, Monika; Klajnert, Barbara; Lisowska, Katarzyna; Caminade, Anne-Marie; Bousmina, Mostapha; Bryszewska, Maria; Majoral, Jean Pierre

    2012-03-05

    Some biological properties of eight dendrimers incorporating both phosphorus linkages and viologen units within their cascade structure or at the periphery were investigated for the first time. In particular cytotoxicity, hemotoxicity, and antimicrobial and antifungal activity of these new macromolecules were examined. Even if for example all these species exhibited good antimicrobial properties, it was demonstrated that their behavior strongly depends on several parameters as their size and molecular weight, the number of viologen units and the nature of the terminal groups.

  6. Optically nonlinear energy transfer in light-harvesting dendrimers

    OpenAIRE

    Andrews, David; Bradshaw, DS

    2004-01-01

    Dendrimeric polymers are the subject of intense research activity geared towards their implementation in nanodevice applications such as energy harvesting systems,organic light-emitting diodes, photosensitizers, low-threshold lasers, and quantum logic elements, etc. A recent development in this area has been the construction of dendrimers specifically designed to exhibit novel forms of optical nonlinearity, exploiting the unique properties of these materials at high levels of photon flux. Sta...

  7. Blue Light Emitting Polyphenylene Dendrimers with Bipolar Charge Transport Moieties

    Directory of Open Access Journals (Sweden)

    Guang Zhang

    2016-10-01

    Full Text Available Two light-emitting polyphenylene dendrimers with both hole and electron transporting moieties were synthesized and characterized. Both molecules exhibited pure blue emission solely from the pyrene core and efficient surface-to-core energy transfers when characterized in a nonpolar environment. In particular, the carbazole- and oxadiazole-functionalized dendrimer (D1 manifested a pure blue emission from the pyrene core without showing intramolecular charge transfer (ICT in environments with increasing polarity. On the other hand, the triphenylamine- and oxadiazole-functionalized one (D2 displayed notable ICT with dual emission from both the core and an ICT state in highly polar solvents. D1, in a three-layer organic light emitting diode (OLED by solution processing gave a pure blue emission with Commission Internationale de l’Éclairage 1931 CIE xy = (0.16, 0.12, a peak current efficiency of 0.21 cd/A and a peak luminance of 2700 cd/m2. This represents the first reported pure blue dendrimer emitter with bipolar charge transport and surface-to-core energy transfer in OLEDs.

  8. Blue Light Emitting Polyphenylene Dendrimers with Bipolar Charge Transport Moieties.

    Science.gov (United States)

    Zhang, Guang; Auer-Berger, Manuel; Gehrig, Dominik W; Blom, Paul W M; Baumgarten, Martin; Schollmeyer, Dieter; List-Kratochvil, E J W; Müllen, Klaus

    2016-10-20

    Two light-emitting polyphenylene dendrimers with both hole and electron transporting moieties were synthesized and characterized. Both molecules exhibited pure blue emission solely from the pyrene core and efficient surface-to-core energy transfers when characterized in a nonpolar environment. In particular, the carbazole- and oxadiazole-functionalized dendrimer ( D1 ) manifested a pure blue emission from the pyrene core without showing intramolecular charge transfer (ICT) in environments with increasing polarity. On the other hand, the triphenylamine- and oxadiazole-functionalized one ( D2 ) displayed notable ICT with dual emission from both the core and an ICT state in highly polar solvents. D1 , in a three-layer organic light emitting diode (OLED) by solution processing gave a pure blue emission with Commission Internationale de l'Éclairage 1931 CIE xy = (0.16, 0.12), a peak current efficiency of 0.21 cd/A and a peak luminance of 2700 cd/m². This represents the first reported pure blue dendrimer emitter with bipolar charge transport and surface-to-core energy transfer in OLEDs.

  9. Structural analysis of binding functionality of folic acid-PEG dendrimers against folate receptor.

    Science.gov (United States)

    Sampogna-Mireles, Diana; Araya-Durán, Ingrid D; Márquez-Miranda, Valeria; Valencia-Gallegos, Jesús A; González-Nilo, Fernando D

    2017-03-01

    Dendrimers functionalized with folic acid (FA) are drug delivery systems that can selectively target cancer cells with folate receptors (FR-α) overexpression. Incorporation of polyethylene glycol (PEG) can enhance dendrimers solubility and pharmacokinetics, but ligand-receptor binding must not be affected. In this work we characterized, at atomic level, the binding functionality of conventional site-specific dendrimers conjugated with FA with PEG 750 or PEG 3350 as a linker. After Molecular Dynamics simulation, we observed that both PEG's did not interfere over ligand-receptor binding functionality. Although binding kinetics could be notably affected, the folate fragment from both dendrimers remained exposed to the solvent before approaching selectively to FR-α. PEG 3350 provided better solubility and protection from enzymatic degradation to the dendrimer than PEG 750. Also, FA-PEG3350 dendrimer showed a slightly better interaction with FR-α than FA-PEG750 dendrimer. Therefore, theoretical evidence supports that both dendrimers are suitable as drug delivery systems for cancer therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Electron Transfer in Methylene-Blue-Labeled G3 Dendrimers Tethered to Gold

    DEFF Research Database (Denmark)

    Álvarez-Martos, Isabel; Kartashov, Andrey; Ferapontova, Elena

    2016-01-01

    , and their dependence on the dendrimer surface packing, contribute to both mechanistic pathways. Electrical wiring of horse-radish peroxidase and hexose oxidase by using MB-labeled dendrimers allowed the bioelectrocatalytic reduction of H2O2 and oxidation of glucose by these enzymes. The demonstrated electrical...

  11. Structural Distortion of Dendrimers on Gold Surfaces: A Tapping-Mode AFM Investigation

    National Research Council Canada - National Science Library

    Hierlemann, A

    1998-01-01

    .... The individual dendrimer molecules forming a monolayer were clearly imaged. Upon exposure to hexadecanethiol, the shapes of individual dendrimers change and they become taller and narrower as more stable thiol-Au bonds replace some of the amine-Au bonds...

  12. Proton-conductive materials formed by coumarin photocrosslinked ionic liquid crystal dendrimers

    NARCIS (Netherlands)

    Concellon, A.; Liang, T.; Schenning, A.P.H.J.; Luis Serrano, J.; Romero, P.; Marcos, M.

    2018-01-01

    In this work, we have successfully examined for the first time the use of ionic dendrimers as building blocks for the preparation of 1D and 2D proton conductive materials. For this purpose, a new family of liquid crystalline dendrimers has been synthesized by ionic self-assembly of poly(amidoamine)

  13. Molecular dynamics study of charged dendrimers in salt-free solution : effect of counterions

    NARCIS (Netherlands)

    Gurtovenko, A.A.; Lyulin, S.V.; Karttunen, M.E.J.; Vattulainen, I.

    2006-01-01

    Polyamidoamine dendrimers, being protonated under physiological conditions, represent a promising class of nonviral, nanosized vectors for drug and gene delivery. We performed extensive molecular dynamics simulations of a generic model dendrimer in a salt-free solution with dendrimer’s terminal

  14. Expand classical drug administration ways by emerging routes using dendrimer drug delivery systems: a concise overview.

    Science.gov (United States)

    Mignani, Serge; El Kazzouli, Saïd; Bousmina, Mosto; Majoral, Jean-Pierre

    2013-10-01

    Drugs are introduced into the body by numerous routes such as enteral (oral, sublingual and rectum administration), parenteral (intravascular, intramuscular, subcutaneous and inhalation administration), or topical (skin and mucosal membranes). Each route has specific purposes, advantages and disadvantages. Today, the oral route remains the preferred one for different reasons such as ease and compliance by patients. Several nanoformulated drugs have been already approved by the FDA, such as Abelcet®, Doxil®, Abraxane® or Vivagel®(Starpharma) which is an anionic G4-poly(L-lysine)-type dendrimer showing potent topical vaginal microbicide activity. Numerous biochemical studies, as well as biological and pharmacological applications of both dendrimer based products (dendrimers as therapeutic compounds per se, like Vivagel®) and dendrimers as drug carriers (covalent conjugation or noncovalent encapsulation of drugs) were described. It is widely known that due to their outstanding physical and chemical properties, dendrimers afforded improvement of corresponding carried-drugs as dendrimer-drug complexes or conjugates (versus plain drug) such as biodistribution and pharmacokinetic behaviors. The purpose of this manuscript is to review the recent progresses of dendrimers as nanoscale drug delivery systems for the delivery of drugs using enteral, parenteral and topical routes. In particular, we focus our attention on the emerging and promising routes such as oral, transdermal, ocular and transmucosal routes using dendrimers as delivery systems. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. pH and generation dependent morphologies of PAMAM dendrimers on a graphene substrate.

    Science.gov (United States)

    Gosika, Mounika; Maiti, Prabal K

    2018-03-07

    The adsorption of PAMAM dendrimers at solid/water interfaces has been extensively studied, and is mainly driven by electrostatic and van der Waals interactions between the substrate and the dendrimers. However, the pH dependence of the adsorption driven predominantly by the van der Waals interactions is poorly explored, although it is crucial for investigating the potentiality of these dendrimers in supercapacitors and surface patterning. Motivated by this aspect, we have studied the adsorption behavior of PAMAM dendrimers of generations 2 (G2) to 5 (G5) with pH and salt concentration variation, on a charge neutral graphene substrate, using fully atomistic molecular dynamics simulations. The instantaneous snapshots from our simulations illustrate that the dendrimers deform significantly from their bulk structures. Based on various structural property calculations, we classify the adsorbed dendrimer morphologies into five categories and map them to a phase diagram. Interestingly, the morphologies we report here have striking analogies with those reported in star-polymer adsorption studies. From the fractional contacts and other structural property analyses we find that the deformations are more pronounced at neutral pH as compared to high and low pH. Higher generation dendrimers resist deformation following the deformation trend, G2 > G3 > G4 > G5 at any given pH level. As the adsorption here is mainly driven by van der Waals interactions, we observe no desorption of the dendrimers as the salt molarity is increased, unlike that reported in the electrostatically driven adsorption studies.

  16. Dendrimers destabilize proteins in a generation-dependent manner involving electrostatic interactions

    DEFF Research Database (Denmark)

    Gichm, Lise; Christensen, Casper; Boas, Ulrik

    2008-01-01

    Dendrimers are well-defined chemical polymers with a characteristic branching pattern that gives rise to attractive features such as antibacterial and antitumor activities as well as drug delivery properties. In addition, dendrimers can solubilize prion protein aggregates at very low concentratio...

  17. Paramagnetic NMR investigation of dendrimer-based host-guest interactions.

    Directory of Open Access Journals (Sweden)

    Fei Wang

    Full Text Available In this study, the host-guest behavior of poly(amidoamine (PAMAM dendrimers bearing amine, hydroxyl, or carboxylate surface functionalities were investigated by paramagnetic NMR studies. 2,2,6,6-Tetramethylpiperidinyloxy (TEMPO derivatives were used as paramagnetic guest molecules. The results showed that TEMPO-COOH significantly broaden the ¹H NMR peaks of amine- and hydroxyl-terminated PAMAM dendrimers. In comparison, no paramagnetic relaxation enhancement (PRE was observed between TEMPO-NH₂, TEMPO-OH and the three types of PAMAM dendrimers. The PRE phenomenon observed is correlated with the encapsulation of TEMPO-COOH within dendrimer pockets. Protonation of the tertiary amine groups within PAMAM dendrimers plays an important role during this process. Interestingly, the absence of TEMPO-COOH encapsulation within carboxylate-terminated PAMAM dendrimer is observed due to the repulsion of TEMPO-COO- anion and anionic dendrimer surface. The combination of paramagnetic probes and ¹H NMR linewidth analysis can be used as a powerful tool in the analysis of dendrimer-based host-guest systems.

  18. Molecular dynamics simulation of coarse-grained poly(L-lysine) dendrimers.

    Science.gov (United States)

    Rahimi, Ali; Amjad-Iranagh, Sepideh; Modarress, Hamid

    2016-03-01

    Poly(L-lysine) (PLL) dendrimer are amino acid based macromolecules and can be used as drug delivery agents. Their branched structure allows them to be functionalized by various groups to encapsulate drug agents into their structure. In this work, at first, an attempt was made on all-atom simulation of PLL dendrimer of different generations. Based on all-atom results, a course-grained model of this dendrimer was designed and its parameters were determined, to be used for simulation of three generations of PLL dendrimer, at two pHs. Similar to the all-atom, the coarse-grained results indicated that by increasing the generation, the dendrimer becomes more spherical. At pH 7, the dendrimer had larger size, whereas at pH 12, due to back folding of branching chains, they had the tendency to penetrate into the inner layers. The calculated radial probability and radial distribution functions confirm that at pH 7, the PLL dendrimer has more cavities and as a result it can encapsulate more water molecules into its inner structure. By calculating the moment of inertia and the aspect ratio, the formation of spherical structure for PLL dendrimer was confirmed.

  19. Dynamics of complexation of a charged dendrimer by linear polyelectrolyte: Computer modelling

    NARCIS (Netherlands)

    Lyulin, S.V.; Darinskii, A.A.; Lyulin, A.V.

    2007-01-01

    Brownian-dynamics simulations have been performed for complexes formed by a charged dendrimer and a long oppositely charged linear polyelectrolyte when overcharging phenomenon is always observed. After a complex formation the orientational mobility of the individual dendrimer bonds, the fluctuations

  20. Photo-physical and structural interactions between viologen phosphorus-based dendrimers and human serum albumin

    International Nuclear Information System (INIS)

    Ciepluch, Karol; Katir, Nadia; El Kadib, Abdelkrim; Weber, Monika; Caminade, Anne-Marie; Bousmina, Mostapha; Pierre Majoral, Jean; Bryszewska, Maria

    2012-01-01

    This work deals with photo-physical and structural interactions between viologen phosphorus dendrimers and human serum albumin (HSA). Viologens are derivatives of 4,4′-bipyridinium salts. Aiming to rationalize the parameters governing such interactions eight types of these polycationic dendrimers in which the generation, the number of charges, the nature of the core and of the terminal groups vary from one to another, were designed and used. The influence of viologen-based dendrimers' on human serum albumin has been investigated. The photo-physical interactions of the two systems have been monitored by fluorescence quenching of free L-tryptophan and of HSA tryptophan residue. Additionally, using circular dichroism (CD) the effect of dendrimers on the secondary structure of albumin was measured. The obtained results show that viologen dendrimers interact with human serum albumin quenching its fluorescence either by collisional (dynamic) way or by forming complexes in a ground state (static quenching). In some cases the quenching is accompanied by changes of the secondary structure of HSA. - Highlights: ► Photo-physical interactions between viologen phosphorus dendrimers and human serum albumin (HSA) were investigated. ► The viologen dendrimers can quench the fluorescence of tryptophan in HSA. ► CD spectra to explain the changes in secondary structure of albumin after exposition of dendrimers.

  1. Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy.

    Science.gov (United States)

    Narsireddy, Amreddy; Vijayashree, Kurra; Adimoolam, Mahesh G; Manorama, Sunkara V; Rao, Nalam M

    2015-01-01

    Challenges in photodynamic therapy (PDT) include development of efficient near infrared-sensitive photosensitizers (5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphine [PS]) and targeted delivery of PS to the tumor tissue. In this study, a dual functional dendrimer was synthesized for targeted PDT. For targeting, a poly(amidoamine) dendrimer (G4) was conjugated with a PS and a nitrilotriacetic acid (NTA) group. A peptide specific to human epidermal growth factor 2 was expressed in Escherichia coli with a His-tag and was specifically bound to the NTA group on the dendrimer. Reaction conditions were optimized to result in dendrimers with PS and the NTA at a fractional occupancy of 50% and 15%, respectively. The dendrimers were characterized by nuclear magnetic resonance, matrix-assisted laser desorption/ionization, absorbance, and fluorescence spectroscopy. Using PS fluorescence, cell uptake of these particles was confirmed by confocal microscopy and fluorescence-activated cell sorting. PS-dendrimers are more efficient than free PS in PDT-mediated cell death assays in HER2 positive cells, SK-OV-3. Similar effects were absent in HER2 negative cell line, MCF-7. Compared to free PS, the PS-dendrimers have shown significant tumor suppression in a xenograft animal tumor model. Conjugation of a PS with dendrimers and with a targeting agent has enhanced photodynamic therapeutic effects of the PS.

  2. Transport of dendrimer nanocarriers through epithelial cells via the transcellular route.

    Science.gov (United States)

    Jevprasesphant, Rachaneekorn; Penny, Jeffrey; Attwood, David; D'Emanuele, Antony

    2004-06-18

    The mechanism of transport of G3 PAMAM and surface-modified (with lauroyl chains) G3 PAMAM dendrimer nanocarriers across Caco-2 cell monolayers has been investigated. Flow-cytometry studies following quenching of extracellular fluorescence demonstrated the cellular internalisation of dendrimers. Optical sectioning of cells incubated with fluorescein isothiocyanate (FITC)-conjugated dendrimer and lauroyl-dendrimer using confocal laser scanning microscopy revealed colocalisation of a marker for cell nuclei (4',6-diamidino-2-phenylindole, DAPI) and FITC fluorescence, also suggesting cellular internalisation of dendrimers. Transmission electron microscopic analyses of cells incubated with gold-labelled G3 PAMAM dendrimers confirmed endocytosis-mediated cellular internalisation when dendrimers were applied to the apical domain of Caco-2 cells. These findings are in agreement with our previous studies using Caco-2 cell monolayers that showed a significant decrease of dendrimer uptake in the presence of colchicine (endocytosis inhibitor) and when temperature was reduced from 37 to 4 degrees C. Copyright 2004 Elsevier B.V.

  3. Diglycolamide-functionalized dendrimers : Studies on Americium(III) pertraction from radioactive waste

    NARCIS (Netherlands)

    Ansari, Seraj A.; Mohapatra, Prasanta K.; Leoncini, Andrea; Huskens, Jurriaan; Verboom, Willem

    2017-01-01

    Diglycolamide (DGA)-functionalized poly(propylene imine) diaminobutane dendrimers were evaluated as the carrier in supported liquid membranes (SLMs) for selective recovery of trivalent actinides over uranium. The 0, 1st, and 2nd generation dendrimers with 2, 4, and 8 DGA moieties, termed as LI, LII,

  4. Endocytic Uptake, Transport and Macromolecular Interactions of Anionic PAMAM Dendrimers within Lung Tissue.

    Science.gov (United States)

    Morris, Christopher J; Aljayyoussi, Ghaith; Mansour, Omar; Griffiths, Peter; Gumbleton, Mark

    2017-12-01

    Polyamidoamine (PAMAM) dendrimers are a promising class of nanocarrier with applications in both small and large molecule drug delivery. Here we report a comprehensive evaluation of the uptake and transport pathways that contribute to the lung disposition of dendrimers. Anionic PAMAM dendrimers and control dextran probes were applied to an isolated perfused rat lung (IPRL) model and lung epithelial monolayers. Endocytosis pathways were examined in primary alveolar epithelial cultures by confocal microscopy. Molecular interactions of dendrimers with protein and lipid lung fluid components were studied using small angle neutron scattering (SANS). Dendrimers were absorbed across the intact lung via a passive, size-dependent transport pathway at rates slower than dextrans of similar molecular sizes. SANS investigations of concentration-dependent PAMAM transport in the IPRL confirmed no aggregation of PAMAMs with either albumin or dipalmitoylphosphatidylcholine lung lining fluid components. Distinct endocytic compartments were identified within primary alveolar epithelial cells and their functionality in the rapid uptake of fluorescent dendrimers and model macromolecular probes was confirmed by co-localisation studies. PAMAM dendrimers display favourable lung biocompatibility but modest lung to blood absorption kinetics. These data support the investigation of dendrimer-based carriers for controlled-release drug delivery to the deep lung.

  5. Regional Morphology and Transport of PAMAM Dendrimers Across Isolated Rat Intestinal Tissue.

    Science.gov (United States)

    Hubbard, Dallin; Bond, Tanner; Ghandehari, Hamidreza

    2015-12-01

    Intestinal permeability of PAMAM dendrimers has been observed, giving rationale for their use in oral drug delivery as potential carriers of associated molecules. This study assessed the apparent permeability coefficients (Papp) of dendrimers across isolated rat intestinal regional mucosae, along with estimation of the maximum non-toxic concentration. Caco-2 monolayers were also used to assess the comparative Papp values between isolated mucosae and cell culture models. Concentrations from 0.1 to 10 mM of anionic and cationic dendrimers were tested in mucosae to assess their Papp, membrane TEER, [(14)C]-mannitol Papp, and histology. 0.1 mM concentrations of dendrimers were assessed over 120 min in Caco-2 cell monolayers as concentrations above that were cytotoxic. Jejunal transport of dendrimers was higher than transport in colonic epithelium. Monolayer Papp values of dendrimers were comparable to those of jejunal mucosae. Mucosae exposed to dendrimer concentrations of 10 mM for 120 min caused significant reduction in TEER and changes in tissue morphology; however, G3.5 was the only analogue that caused significant TEER reduction and morphological changes at 1 mM concentrations. Transport in jejunal mucosae appears to be the greatest indicating that the small intestinal will be the most likely region to target for oral drug delivery using PAMAM dendrimers. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Photo-physical and structural interactions between viologen phosphorus-based dendrimers and human serum albumin

    Energy Technology Data Exchange (ETDEWEB)

    Ciepluch, Karol, E-mail: ciepluch@biol.uni.lodz.pl [Department of General Biophysics, University of Lodz, 141/143 Pomorska St., 90-236 Lodz (Poland); Katir, Nadia [Laboratoire de Chimie de Coordination du CNRS (LCC), 205 route de Narbonne, F-31077 Toulouse cedex 4 (France); Institute of Nanomaterials and Nanotechnology (INANOTECH)-MAScIR (Moroccan Foundation for Advanced Science, Innovation and Research), ENSET, Avenue de l' Armee Royale, Madinat El Irfane, 10100 Rabat (Morocco); El Kadib, Abdelkrim [Institute of Nanomaterials and Nanotechnology (INANOTECH)-MAScIR (Moroccan Foundation for Advanced Science, Innovation and Research), ENSET, Avenue de l' Armee Royale, Madinat El Irfane, 10100 Rabat (Morocco); Weber, Monika [Department of General Biophysics, University of Lodz, 141/143 Pomorska St., 90-236 Lodz (Poland); Caminade, Anne-Marie [Laboratoire de Chimie de Coordination du CNRS (LCC), 205 route de Narbonne, F-31077 Toulouse cedex 4 (France); Bousmina, Mostapha [Hassan II Academy of Sciences and Technology, Avenue MVI, Km4, 10220 Rabat (Morocco); Pierre Majoral, Jean [Laboratoire de Chimie de Coordination du CNRS (LCC), 205 route de Narbonne, F-31077 Toulouse cedex 4 (France); Hassan II Academy of Sciences and Technology, Avenue MVI, Km4, 10220 Rabat (Morocco); Bryszewska, Maria [Department of General Biophysics, University of Lodz, 141/143 Pomorska St., 90-236 Lodz (Poland)

    2012-06-15

    This work deals with photo-physical and structural interactions between viologen phosphorus dendrimers and human serum albumin (HSA). Viologens are derivatives of 4,4 Prime -bipyridinium salts. Aiming to rationalize the parameters governing such interactions eight types of these polycationic dendrimers in which the generation, the number of charges, the nature of the core and of the terminal groups vary from one to another, were designed and used. The influence of viologen-based dendrimers' on human serum albumin has been investigated. The photo-physical interactions of the two systems have been monitored by fluorescence quenching of free L-tryptophan and of HSA tryptophan residue. Additionally, using circular dichroism (CD) the effect of dendrimers on the secondary structure of albumin was measured. The obtained results show that viologen dendrimers interact with human serum albumin quenching its fluorescence either by collisional (dynamic) way or by forming complexes in a ground state (static quenching). In some cases the quenching is accompanied by changes of the secondary structure of HSA. - Highlights: Black-Right-Pointing-Pointer Photo-physical interactions between viologen phosphorus dendrimers and human serum albumin (HSA) were investigated. Black-Right-Pointing-Pointer The viologen dendrimers can quench the fluorescence of tryptophan in HSA. Black-Right-Pointing-Pointer CD spectra to explain the changes in secondary structure of albumin after exposition of dendrimers.

  7. Functionalized Poly(propylene imine) Dendrimers as Novel Phase Transfer Catalyst in Supercritical Cabon Dioxide

    NARCIS (Netherlands)

    Goetheer, E.L.V.; Baars, M.W.P.L.; Broeke, van den L.J.P.; Meijer, E.W.; Keurentjes, J.T.F.

    2000-01-01

    Perfluoro-functionalized poly(propylene imine) dendrimers have been used as reactive extractants for anionic species and as phase transfer catalysts for two types of reactions. Different generations of dendrimers have been used for applications in carbon dioxide. First, the reactive extraction of

  8. Synthesis and protonation behavior of carboxylate-functionalized poly(propylene imine) dendrimers

    NARCIS (Netherlands)

    Duijvenbode, van R.C.; Rajanayagam, A.; Koper, G.J.M.; Baars, M.W.P.L.; Waal, de B.F.M.; Meijer, E.W.; Borkovec, M.

    2000-01-01

    Five generations of carboxylate-functionalized poly(propyleneimine) dendrimers have been synthesized starting from a double Michael addition of amine-functionalized poly(propyleneimine) dendrimers to methyl acrylate followed by basic hydrolysis using LiOH in a water/methanol mixture. The dendritic

  9. Trapping time statistics and efficiency of transport of optical excitations in dendrimers

    Science.gov (United States)

    Heijs, Dirk-Jan; Malyshev, Victor A.; Knoester, Jasper

    2004-09-01

    We theoretically study the trapping time distribution and the efficiency of the excitation energy transport in dendritic systems. Trapping of excitations, created at the periphery of the dendrimer, on a trap located at its core, is used as a probe of the efficiency of the energy transport across the dendrimer. The transport process is treated as incoherent hopping of excitations between nearest-neighbor dendrimer units and is described using a rate equation. We account for radiative and nonradiative decay of the excitations while diffusing across the dendrimer. We derive exact expressions for the Laplace transform of the trapping time distribution and the efficiency of trapping, and analyze those for various realizations of the energy bias, number of dendrimer generations, and relative rates for decay and hopping. We show that the essential parameter that governs the trapping efficiency is the product of the on-site excitation decay rate and the trapping time (mean first passage time) in the absence of decay.

  10. Different patterns of nuclear and mitochondrial penetration by the G3 PAMAM dendrimer and its biotin–pyridoxal bioconjugate BC-PAMAM in normal and cancer cells in vitro

    Science.gov (United States)

    Uram, Łukasz; Szuster, Magdalena; Filipowicz, Aleksandra; Gargasz, Krzysztof; Wołowiec, Stanisław; Wałajtys-Rode, Elżbieta

    2015-01-01

    The intracellular localization and colocalization of a fluorescently labeled G3 amine-terminated cationic polyamidoamine (PAMAM) dendrimer and its biotin–pyridoxal (BC-PAMAM) bioconjugate were investigated in a concentration-dependent manner in normal human fibroblast (BJ) and squamous epithelial carcinoma (SCC-15) cell lines. After 24 hours treatment, both cell lines revealed different patterns of intracellular dendrimer accumulation depending on their cytotoxic effects. Cancer cells exhibited much higher (20-fold) tolerance for native PAMAM treatment than fibroblasts, whereas BC-PAMAM was significantly toxic only for fibroblasts at 50 µM concentration. Fibroblasts accumulated the native and bioconjugated dendrimers in a concentration-dependent manner at nontoxic range of concentration, with significantly lower bioconjugate loading. After reaching the cytotoxicity level, fluorescein isothiocyanate-PAMAM accumulation remains at high, comparable level. In cancer cells, native PAMAM loading at higher, but not cytotoxic concentrations, was kept at constant level with a sharp increase at toxic concentration. Mander’s coefficient calculated for fibroblasts and cancer cells confirmed more efficient native PAMAM penetration as compared to BC-PAMAM. Significant differences in nuclear dendrimer penetration were observed for both cell lines. In cancer cells, PAMAM signals amounted to ~25%–35% of the total nuclei area at all investigated concentrations, with lower level (15%–25%) observed for BC-PAMAM. In fibroblasts, the dendrimer nuclear signal amounted to 15% at nontoxic and up to 70% at toxic concentrations, whereas BC-PAMAM remained at a lower concentration-dependent level (0.3%–20%). Mitochondrial localization of PAMAM and BC-PAMAM revealed similar patterns in both cell lines, depending on the extracellular dendrimer concentration, and presented significantly lower signals from BC-PAMAM, which correlated well with the cytotoxicity. PMID:26379435

  11. Single multivalent vaccination boosted by trickle larval infection confers protection against experimental lymphatic filariasis

    Science.gov (United States)

    Joseph, SK; Ramaswamy, K

    2013-01-01

    The multivalent vaccine BmHAT, consisting of the Brugia malayi infective larval (L3) antigens heat shock protein12.6 (HSP12.6), abundant larval transcript-2 (ALT-2) and tetraspanin large extra cellular loop (TSP-LEL), was shown to be protective in rodent models from our laboratory. We hypothesize that since these antigens were identified using protective antibodies from immune endemic normal individuals, the multivalent vaccine can be augmented by natural L3 infections providing protection to the vaccinated host. This hypothesis was tested using single dose of DNA and Protein or Protein alone of the BmHAT vaccination in gerbils followed by live trickle L3 infection as booster dose. Vaccine-induced protection in gerbils was determined by worm establishment, micropore chamber assay and by antibody dependant cell cytotoxicity (ADCC) assay. Results were compared with the traditional prime-boost vaccination regimen. Gerbils vaccinated with BmHAT and boosted with L3 trickle infection were protected 51% (BmHAT DNA-Protein) and 48% (BmHAT Protein) respectively. BmHAT vaccination plus L3 trickle booster generated significant titer of antigen-specific IgG antibodies comparable to the traditional prime boost vaccination approach. BmHAT vaccination plus L3 trickle booster also generated antigen-specific cells in the spleen of vaccinated animals and these cells secreted predominantly IFN-γ and IL-4 in response to the vaccine antigens. These studies thus show that single dose of BmHAT multivalent vaccination followed by L3 trickle booster infection can confer significant protection against lymphatic filariasis. PMID:23735679

  12. Multivalent conjugates of basic fibroblast growth factor enhance in vitro proliferation and migration of endothelial cells.

    Science.gov (United States)

    Zbinden, Aline; Browne, Shane; Altiok, Eda I; Svedlund, Felicia L; Jackson, Wesley M; Healy, Kevin E

    2018-05-01

    Growth factors hold great promise for regenerative therapies. However, their clinical use has been halted by poor efficacy and rapid clearance from tissue, necessitating the delivery of extremely high doses to achieve clinical effectiveness which has raised safety concerns. Thus, strategies to either enhance growth factor activity at low doses or to increase their residence time within target tissues are necessary for clinical success. In this study, we generated multivalent conjugates (MVCs) of basic fibroblast growth factor (bFGF), a key growth factor involved in angiogenesis and wound healing, to hyaluronic acid (HyA) polymer chains. Multivalent bFGF conjugates (mvbFGF) were fabricated with minimal non-specific interaction observed between bFGF and the HyA chain. The hydrodynamic radii of mvbFGF ranged from ∼50 to ∼75 nm for conjugation ratios of bFGF to HyA chains at low (10 : 1) and high (30 : 1) feed ratios, respectively. The mvbFGF demonstrated enhanced bioactivity compared to unconjugated bFGF in assays of cell proliferation and migration, processes critical to angiogenesis and tissue regeneration. The 30 : 1 mvbFGF outperformed the 10 : 1 conjugate, which could be due to either FGF receptor clustering or interference with receptor mediated internalization and signal deactivation. This study simultaneously investigated the role of both protein to polymer ratio and multivalent conjugate size on their bioactivity, and determined that increasing the protein-to-polymer ratio and conjugate size resulted in greater cell bioactivity.

  13. Single multivalent vaccination boosted by trickle larval infection confers protection against experimental lymphatic filariasis.

    Science.gov (United States)

    Joseph, S K; Ramaswamy, K

    2013-07-18

    The multivalent vaccine BmHAT, consisting of the Brugia malayi infective larval (L3) antigens heat shock protein12.6 (HSP12.6), abundant larval transcript-2 (ALT-2) and tetraspanin large extra cellular loop (TSP-LEL), was shown to be protective in rodent models from our laboratory. We hypothesize that since these antigens were identified using protective antibodies from immune endemic normal individuals, the multivalent vaccine can be augmented by natural L3 infections providing protection to the vaccinated host. This hypothesis was tested using single dose of DNA and protein or protein alone of the BmHAT vaccination in gerbils followed by live trickle L3 infection as booster dose. Vaccine-induced protection in gerbils was determined by worm establishment, micropore chamber assay and by antibody dependant cell cytotoxicity (ADCC) assay. Results were compared with the traditional prime-boost vaccination regimen. Gerbils vaccinated with BmHAT and boosted with L3 trickle infection were protected 51% (BmHAT DNA-protein) and 48% (BmHAT protein) respectively. BmHAT vaccination plus L3 trickle booster generated significant titer of antigen-specific IgG antibodies comparable to the traditional prime boost vaccination approach. BmHAT vaccination plus L3 trickle booster also generated antigen-specific cells in the spleen of vaccinated animals and these cells secreted predominantly IFN-γ and IL-4 in response to the vaccine antigens. These studies thus show that single dose of BmHAT multivalent vaccination followed by L3 trickle booster infection can confer significant protection against lymphatic filariasis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Probing the binding of cationic lipids with dendrimers.

    Science.gov (United States)

    Mandeville, J S; Bourassa, P; Tajmir-Riahi, H A

    2013-01-14

    Polycationic polymers are used extensively in biology to disrupt cell membranes and thus enhance the transport of materials into the cell. We report the bindings of several lipids cholesterol (Chol), 1,2-dioleoyl-3-trimethylammonium-propane(DOTAP), dioctadecyldimethylammoniumbromide (DDAB), and dioleoylphosphatidylethanolamine (DOPE) to dendrimers of different compositions such as mPEG-PAMAM (G3), mPEG-PAMAM (G4), and PAMAM (G4) under physiological conditions. FTIR, UV-visible spectroscopic, methods and molecular modeling were used to analyze the lipid binding mode, the binding constant, and the effects of lipid complexation on the dendrimer structure. The structural analysis showed that lipids bind dendrimers through both hydrophilic and hydrophobic contacts with overall binding constants of K(chol-mPEG-G3) = 1.7 × 10(3) M(-1), K(chol-mPEG-PAMAM-G4) = 2.7 × 10(3) M(-1), K(chol-PAMAM-G4) = 1.0 × 10(3) M(-1), K(DOPE-mPEG-G3) = 1.5 × 10(3) M(-1), K(DOPE-mPEG-PAMAM-G4) = 1.6 × 10(3) M(-1), K(DOPE-PAMAM-G4) = 5.3 × 10(2) M(-1), K(DDAB-mPEG-G3) = 1.5 × 10(3) M(-1), K(DDAB-mPEG-PAMAM-G4) = 1.9 × 10(2) M(-1), K(DDAB-PAMAM-G4) = 7.0 × 10(2) M(-1), K(DOTAP-mPEG-G3) = 1.9 × 10(3) M(-1), K(DOTAP-mPEG-PAMAM-G4) = 1.5 × 10(3) M(-1), and K(DOTAP-PAMAM-G4) = 5.7 × 10(2) M(-1). Weaker interaction was observed as dendrimer cationic charges increased. The free binding energies from docking were -5.15 (cholesterol), -5.79 (DDAB), and -5.36 kcal/mol (DOTAP) with the order of stability DDAB-PAMAM-G-4 > DOTAP-PAMAM-G4 > cholesterol-PAMAM-G4, consistent with the spectroscopic results. Dendrimers might act as carriers to transport lipids in vitro.

  15. Mannose-decorated cyclodextrin vesicles: The interplay of multivalency and surface density in lectin–carbohydrate recognition

    Directory of Open Access Journals (Sweden)

    Ulrike Kauscher

    2012-09-01

    Full Text Available Cyclodextrin vesicles are versatile models for biological cell membranes since they provide a bilayer membrane that can easily be modified by host–guest interactions with functional guest molecules. In this article, we investigate the multivalent interaction of the lectin concanavalin A (ConA with cyclodextrin vesicles decorated with mannose–adamantane conjugates with one, two or three adamantane units as well as one or two mannose units. The carbohydrate–lectin interaction in this artificial, self-assembled glycocalyx was monitored in an agglutination assay by the increase of optical density at 400 nm. It was found that there is a close relation between the carbohydrate density at the cyclodextrin vesicle surface and the multivalent interaction with ConA, and the most efficient interaction (i.e., fastest agglutination at lowest concentration was observed for mannose–adamantane conjugates, in which both the cyclodextrin–adamantane and the lectin–mannose interaction is inherently multivalent.

  16. Self-assembly of heteroleptic dinuclear metallosupramolecular kites from multivalent ligands via social self-sorting

    Directory of Open Access Journals (Sweden)

    Christian Benkhäuser

    2015-05-01

    Full Text Available A Tröger's base-derived racemic bis(1,10-phenanthroline ligand (rac-1 and a bis(2,2'-bipyridine ligand with a central 1,3-diethynylbenzene unit 2 were synthesized. Each of these ligands acts as a multivalent entity for the binding of two copper(I ions. Upon coordination to the metal ions these two ligands undergo selective self-assembly into heteroleptic dinuclear metallosupramolecular kites in a high-fidelity social self-sorting manner as evidenced by NMR spectroscopy and mass spectrometry.

  17. Organic Light-Emitting Diodes Using Multifunctional Phosphorescent Dendrimers with Iridium-Complex Core and Charge-Transporting Dendrons

    Science.gov (United States)

    Tsuzuki, Toshimitsu; Shirasawa, Nobuhiko; Suzuki, Toshiyasu; Tokito, Shizuo

    2005-06-01

    We report a novel class of light-emitting materials for use in organic light-emitting diodes (OLEDs): multifunctional phosphorescent dendrimers that have a phosphorescent core and dendrons based on charge-transporting building blocks. We synthesized first-generation and second-generation dendrimers consisting of a fac-tris(2-phenylpyridine)iridium [Ir(ppy)3] core and hole-transporting phenylcarbazole-based dendrons. Smooth amorphous films of these dendrimers were formed by spin-coating them from solutions. The OLEDs using the dendrimer exhibited bright green or yellowish-green emission from the Ir(ppy)3 core. The OLEDs using the film containing a mixture of the dendrimer and an electron-transporting material exhibited higher efficiency than those using the neat dendrimer film. The external quantum efficiency of OLEDs using the film containing a mixture of the first-generation dendrimer and an electron-transporting material was as high as 7.6%.

  18. Physicochemical and biological properties of self-assembled antisense/poly(amidoamine) dendrimer nanoparticles: the effect of dendrimer generation and charge ratio

    OpenAIRE

    Nomani, Alireza; Haririan, Ismaeil; Rahimnia, Ramin; Fouladdel, Shamileh; Gazori, Tarane; Dinarvand, Rassoul; Omidi, Yadollah; Azizi, Ebrahim

    2010-01-01

    To gain a deeper understanding of the physicochemical phenomenon of self-assembled nanoparticles of different generations and ratios of poly (amidoamine) dendrimer (PAMAM) dendrimer and a short-stranded DNA (antisense oligonucleotide), multiple methods were used to characterize these nanoparticles including photon correlation spectroscopy (PCS); zeta potential measurement; and atomic force microscopy (AFM). PCS and AFM results revealed that, in contrast to larger molecules of DNA, smaller mol...

  19. Dendrimer-based fluorescent indicators: in vitro and in vivo applications.

    Directory of Open Access Journals (Sweden)

    Lorenzo Albertazzi

    Full Text Available BACKGROUND: The development of fluorescent proteins and synthetic molecules whose fluorescence properties are controlled by the environment makes it possible to monitor physiological and pathological events in living systems with minimal perturbation. A large number of small organic dyes are available and routinely used to measure biologically relevant parameters. Unfortunately their application is hindered by a number of limitations stemming from the use of these small molecules in the biological environment. PRINCIPAL FINDINGS: We present a novel dendrimer-based architecture leading to multifunctional sensing elements that can overcome many of these problems. Applications in vitro, in living cells and in vivo are reported. In particular, we image for the first time extracellular pH in the brain in a mouse epilepsy model. CONCLUSION: We believe that the proposed architecture can represent a useful and novel tool in fluorescence imaging that can be widely applied in conjunction with a broad range of sensing dyes and experimental setups.

  20. Wetting and layering transitions in a nano-dendrimer PAMAM structure: Monte Carlo study

    Science.gov (United States)

    Aouini, S.; Ziti, S.; Labrim, H.; Bahmad, L.

    2016-10-01

    This study is based on a nano-model of the dendrimer polyamidoamine (PAMAM). The idea is to examine the magnetic properties of such models in the context of wetting and the layering transitions. The studied system consists of spins σ ={1/2} Ising ferromagnetic in real nanostructure found in different scientific domains. To study this system, we perform Monte Carlo simulations leading to interesting results recapitulated in two classes. The former is the ground state phase diagrams study. The latter is the magnetic properties at non null temperatures. Also, we analyzed the effect of the terms present in the Hamiltonian governing our system such as the external magnetic field and the exchange couplings interactions.

  1. Folic acid-decorated polyamidoamine dendrimer exhibits high tumor uptake and sustained highly localized retention in solid tumors: Its utility for local siRNA delivery.

    Science.gov (United States)

    Xu, Leyuan; Yeudall, W Andrew; Yang, Hu

    2017-07-15

    The utility of folic acid (FA)-decorated polyamidoamine dendrimer G4 (G4-FA) as a vector was investigated for local delivery of siRNA. In a xenograft HN12 (or HN12-YFP) tumor mouse model of head and neck squamous cell carcinomas (HNSCC), intratumorally (i.t.) injected G4-FA exhibited high tumor uptake and sustained highly localized retention in the tumors according to near infrared (NIR) imaging assessment. siRNA against vascular endothelial growth factor A (siVEGFA) was chosen as a therapeutic modality. Compared to the nontherapeutic treatment groups (PBS solution or dendrimer complexed with nontherapeutic siRNA against green fluorescent protein (siGFP)), G4-FA/siVEGFA showed tumor inhibition effects in single-dose and two-dose regimen studies. In particular, two doses of G4-FA/siVEGFA i.t. administered eight days apart resulted in a more profound inhibition of tumor growth, accompanied with significant reduction in angiogenesis, as judged by CD31 staining and microvessel counts. Tumor size reduction in the two-dose regimen study was ascertained semi-quantitatively by live fluorescence imaging of YFP tumors and independently supported antitumor effects of G4-FA/siVEGFA. Taken together, G4-FA shows high tumor uptake and sustained retention properties, making it a suitable platform for local delivery of siRNAs to treat cancers that are readily accessible such as HNSCC. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and is difficult to transfect for gene therapy. We developed folate receptor (FR)-targeted polyamidoamine (PAMAM) dendrimer for enhanced delivery of genes to HNSCC and gained in-depth understanding of how gene delivery and transfection in head and neck squamous cancer cells can be enhanced via FR-targeted PAMAM dendrimers. The results we report here are encouraging and present latest advances in using dendrimers for cancer therapies, in particular for HNSCC. Our work has demonstrated that localized delivery of FR

  2. Structure-conductivity studies in polymer electrolytes containing multivalent cations

    International Nuclear Information System (INIS)

    Aziz, M.

    1996-05-01

    Understanding the structure - conductivity relationship is of paramount importance for the development of polymer electrolytes. The present studies present the techniques found useful in the elucidation of structure - conductivity relationship in PEO n :ZnBr 2 (n = 8, 1000, 2000, 3000, 4000 and 5000) and PEO n :FeBr x (n= 8, 20 and 50; x = 2 and 3). Local structural studies have been undertaken using X-ray absorption fine structures (XAFS) which includes extended X-ray absorption fine structure (EXAFS) and X-ray absorption near edge structure (XANES). EXAFS provides interatomic distance and coordination numbers of the nearest neighbours and results from the EXAFS studies showed that high conductivity is associated with stretched M - O interatomic distance. In the studies on ultra dilute Zn samples it was found that the cation is highly solvated by the heteroatom forming a tightly bound environment which inhibits local segmental motion thus impeding ion migration. XANES studies on the PEO and modified PEO complexes of NiBr 2 revealed the sensitivity of XANES to the structural differences. XANES on Zn and Fe samples also revealed the sensitivity to changes in interatomic distances reflected in shifts of the white line. The complementary nature of EXAFS and XANES was reflected in the studies conducted. Morphological studies were undertaken employing differential scanning calorimetry (DSC), variable temperature polarising microscopy (VTPM) and atomic force microscopy (AFM). DSC evidences helped to explain the texture of the iron samples during the drying process, and showed transitions between low melting, PEO and high melting spherulites, and VTPM is able to visualise the spherulites present in the samples. AFM has successfully imaged the as cast PEO 8 :FeBr 2 sample and the surface effect causing extra resistance in the impedance spectra could be seen. Conductivity studies were carried out using a.c. impedance spectra. Fe(ll) samples exhibit the typical semicircle

  3. Multivalency at Interfaces: Supramolecular Carbohydrate-Functionalized Graphene Derivatives for Bacterial Capture, Release, and Disinfection.

    Science.gov (United States)

    Qi, Zhenhui; Bharate, Priya; Lai, Chian-Hui; Ziem, Benjamin; Böttcher, Christoph; Schulz, Andrea; Beckert, Fabian; Hatting, Benjamin; Mülhaupt, Rolf; Seeberger, Peter H; Haag, Rainer

    2015-09-09

    A supramolecular carbohydrate-functionalized two-dimensional (2D) surface was designed and synthesized by decorating thermally reduced graphene sheets with multivalent sugar ligands. The formation of host-guest inclusions on the carbon surface provides a versatile strategy, not only to increase the intrinsic water solubility of graphene-based materials, but more importantly to let the desired biofunctional binding groups bind to the surface. Combining the vital recognition role of carbohydrates and the unique 2D large flexible surface area of the graphene sheets, the addition of multivalent sugar ligands makes the resulting carbon material an excellent platform for selectively wrapping and agglutinating Escherichia coli (E. coli). By taking advantage of the responsive property of supramolecular interactions, the captured bacteria can then be partially released by adding a competitive guest. Compared to previously reported scaffolds, the unique thermal IR-absorption properties of graphene derivatives provide a facile method to kill the captured bacteria by IR-laser irradiation of the captured graphene-sugar-E. coli complex.

  4. Lumican as a multivalent effector in wound healing.

    Science.gov (United States)

    Karamanou, Konstantina; Perrot, Gwenn; Maquart, Francois-Xavier; Brézillon, Stéphane

    2018-03-01

    Wound healing, a complex physiological process, is responsible for tissue repair after exposure to destructive stimuli, without resulting in complete functional regeneration. Injuries can be stromal or epithelial, and most cases of wound repair have been studied in the skin and cornea. Lumican, a small leucine-rich proteoglycan, is expressed in the extracellular matrices of several tissues, such as the cornea, cartilage, and skin. This molecule has been shown to regulate collagen fibrillogenesis, keratinocyte phenotypes, and corneal transparency modulation. Lumican is also involved in the extravasation of inflammatory cells and angiogenesis, which are both critical in stromal wound healing. Lumican is the only member of the small leucine-rich proteoglycan family expressed by the epithelia during wound healing. This review summarizes the importance of lumican in wound healing and potential methods of lumican drug delivery to target wound repair are discussed. The involvement of lumican in corneal wound healing is described based on in vitro and in vivo models, with critical emphasis on its underlying mechanisms of action. Similarly, the expression and role of lumican in the healing of other tissues are presented, with emphasis on skin wound healing. Overall, lumican promotes normal wound repair and broadens new therapeutic perspectives for impaired wound healing. Copyright © 2018. Published by Elsevier B.V.

  5. Equilibrium polyelectrolyte bundles with different multivalent counterion concentrations

    Science.gov (United States)

    Sayar, Mehmet; Holm, Christian

    2010-09-01

    We present the results of molecular-dynamics simulations on the salt concentration dependence of the formation of polyelectrolyte bundles in thermodynamic equilibrium. Extending our results on salt-free systems we investigate here deficiency or excess of trivalent counterions in solution. Our results reveal that the trivalent counterion concentration significantly alters the bundle size and size distribution. The onset of bundle formation takes place at earlier Bjerrum length values with increasing trivalent counterion concentration. For the cases of 80%, 95%, and 100% charge compensation via trivalent counterions, the net charge of the bundles decreases with increasing size. We suggest that competition among two different mechanisms, counterion condensation and merger of bundles, leads to a nonmonotonic change in line-charge density with increasing Bjerrum length. The investigated case of having an abundance of trivalent counterions by 200% prohibits such a behavior. In this case, we find that the difference in effective line-charge density of different size bundles diminishes. In fact, the system displays an isoelectric point, where all bundles become charge neutral.

  6. Rational design of dendrimer/lipid nanoassemblies in drug delivery for cancer chemotherapy

    Science.gov (United States)

    Sun, Qihang

    Nanocarriers can minimize the side effects and improve therapeutic efficacy of anticancer drugs. Although some success has been achieved via active or passive drug delivery to tumor cells, the known nanocarriers are far from satisfying therapeutic efficacy expectations. This is because they usually fail in one of the four crucial requirements, that is, to retain drug in blood circulation but release it reliably in tumor cells and to be stealthy in transport in circulation and tumor tissue but sticky upon arrival at the tumor cell. Therefore, the goal of this work is to fabricate nanoassemblies of dendrimers and lipids to address all these challenges. Particularly, nanoassemblies designed and prepared in this work are illustrated to improve the tumor tissue penetration. Examples of dendrimers synthesized in this work are water-insoluble, pH-dependent water-insoluble and water-soluble biodegradable polyester dendrimers. These dendrimers are shown to be encapsulated by commonly used fusogenic and long-circulating lipids to form reliable nanoassemblies. The dendrimer/lipid nanocarriers are used to demonstrate a cascade drug delivery. They are expected to be stable in circulation, due to their appropriately large size, but to release the drug-loaded dendrimers in tumor tissue. The released dendrimers carrying drugs are much smaller and hence expected to have a much deeper penetration throughout the tumor tissue.

  7. Synergistic effect of amino acids modified on dendrimer surface in gene delivery.

    Science.gov (United States)

    Wang, Fei; Wang, Yitong; Wang, Hui; Shao, Naimin; Chen, Yuanyuan; Cheng, Yiyun

    2014-11-01

    Design of an efficient gene vector based on dendrimer remains a great challenge due to the presence of multiple barriers in gene delivery. Single-functionalization on dendrimer cannot overcome all the barriers. In this study, we synthesized a list of single-, dual- and triple-functionalized dendrimers with arginine, phenylalanine and histidine for gene delivery using a one-pot approach. The three amino acids play different roles in gene delivery: arginine is essential in formation of stable complexes, phenylalanine improves cellular uptake efficacy, and histidine increases pH-buffering capacity and minimizes cytotoxicity of the cationic dendrimer. A combination of these amino acids on dendrimer generates a synergistic effect in gene delivery. The dual- and triple-functionalized dendrimers show minimal cytotoxicity on the transfected NIH 3T3 cells. Using this combination strategy, we can obtain triple-functionalized dendrimers with comparable transfection efficacy to several commercial transfection reagents. Such a combination strategy should be applicable to the design of efficient and biocompatible gene vectors for gene delivery. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Development of a Topical Resveratrol Formulation for Commercial Applications Using Dendrimer Nanotechnology.

    Science.gov (United States)

    Pentek, Tyler; Newenhouse, Eric; O'Brien, Brennin; Chauhan, Abhay Singh

    2017-01-14

    Resveratrol (RSV) is well known for its anti-oxidant and anti-aging properties. However, resveratrol is insoluble in water and has stability issues. Recently, efforts were placed to prepare a resveratrol-based advanced anti-aging topical product but it contains harsh organic solvents and oils that could be harmful to the human body and the environment. Hence, we propose the use of a multifunctional dendrimer to solve the solubility and stability issues of resveratrol. A dendrimer-resveratrol complex was prepared, optimized and tested for solubility enhancement, stability in solution and cream dosage forms. We have also developed a high performance liquid chromatography method to measure the resveratrol within the final product. PAMAM dendrimers increased the solubility and stability of resveratrol in water and semisolid dosage forms. Therefore, this product would be water based 'green' formulation devoid of harsh organic solvents and oils and can be safely applied to the skin. Additionally, we have shown that the dendrimer helped to increase overall RSV loading and skin penetration of resveratrol. The dendrimer-RSV formulation was successfully scaled up towards commercialization. Dendrimer with RSV has led to an innovation in anti-aging cream and solutions that could be commercially marketed. Dendrimer-RSV complex could also be added to other product forms for additional purposes and applications.

  9. Neutron Reflectometry Investigations of the Interaction of DNA-PAMAM Dendrimers with Model Biological Membranes

    International Nuclear Information System (INIS)

    Ainalem, M.L.; Rennie, A.R.; Campbell, Richard; Edler, Karen; Nylander, Tommy

    2009-01-01

    The systemic delivery of DNA for gene therapy requires control of DNA compaction by an agent, such a lipid, surfactant or a polymer (e.g. cationic dendrimers) as well as understanding of how this complex interacts with a biological membrane. Poly (amido amine) (PAMAM) dendrimers have been reported to be a promising synthetic gene-transfection agent. We have studied the structure of the complexes formed between DNA and PAMAM dendrimers with SANS, dynamic light scattering and cryo-TEM. Here we noted that the structure of the complex formed strongly depends on the generation of the dendrimer. The results of the adsorption of generation 2 (G2) and 4 (G4) PAMAM dendrimers to surface deposited bilayers, consisting of palmitoyl oleoyl phosphatidyl choline on silicon surface, have been studied using neutron reflectometry (NR). The NR data shows that the dendrimers are able to penetrate the bilayer. However, the complex is less able to penetrate the bilayer, but rather stays on the top of the bilayer. The dendrimers appear slightly flattened on the surface in comparison with their size in bulk as determined by light scattering. We will also report on the interfacial behavior of the DNA-PAMAM complexes at other types of studies of interfaces, important for biomedical applications, where NR has allowed us to determine the layer structure and composition. (author)

  10. Tautomeric forms of PPI dendrimers functionalized with 4-(4′-ethoxybenzoyloxy)salicylaldehyde chromophores

    International Nuclear Information System (INIS)

    Franckevičius, M.; Vaišnoras, R.; Marcos, M.; Serrano, J.L.; Gruodis, A.; Galikova, N.; Gulbinas, V.

    2012-01-01

    Highlights: ► SA chromophore groups are formed by bonding terminal groups to PPI dendrimers. ► SA chromophore groups reveal four most stable tautomeric forms. ► Tautomeric properties of SA groups depend on the dendrimer generation and solvent. ► Aggregation of SA chromophores facilitates formation of the trans-keto tautomers. ► Fluorescence of PPI SA dendrimers is attributed to nπ ∗ states of keto tautomers. -- Abstract: Bonding of the promesogenic unit derived from 4-(4′-ethoxybenzoyloxy)salicylaldehyde to the amino terminated PPI dendrimer chains results in formation of the salicylidenimine chromophore groups. Absorption and fluorescence investigations of the dendrimer solutions supported by the quantum chemistry calculations revealed that the chromophore groups may exist in enol and keto tautomeric forms with relative concentrations depending on the dendrimer generation and solvent. The dendrimer fluorescence is attributed to nπ ∗ states of keto tautomers which may also be formed from excited enol tautomers.

  11. Development of TREN dendrimers over mesoporous SBA-15 for CO2 adsorption

    International Nuclear Information System (INIS)

    Bhagiyalakshmi, Margandan; Park, Sang Do; Cha, Wang Seog; Jang, Hyun Tae

    2010-01-01

    Mesoporous SBA-15 was synthesized using rice husk ash (RHA) as the silica source and their defective Si-OH groups were grafted with tris(2-aminoethyl) amine (TREN) dendrimers generation through step-wise growth technique. The X-ray diffraction (XRD) and nitrogen adsorption/desorption results of parent SBA-15 obtained from RHA, suggests its resemblance with SBA-15 synthesized using conventional silica sources. Furthermore, the nitrogen adsorption/desorption results of SBA-15/TREN dendrimer generations (G1-G3) illustrates the growth of dendrimer inside the mesopores of SBA-15 and their CO 2 adsorption capacity was determined at 25 deg. C. The maximum CO 2 adsorption capacity of 5-6 and 7-8 wt% over second and third dendrimer generation was observed which is discernibly higher than the reported melamine and PAMAM dendrimers. The experimental CO 2 adsorption capacity was found to be less than theoretically calculated CO 2 adsorption capacity due to inter and intra molecular amidation as result of steric hindrance during the dendrimer growth. These SBA-15/TREN dendrimer generations also exhibit thermal stability up to 350 deg. C and CO 2 adsorption capacity remains unaltered upon seven consecutive runs.

  12. PEGylation of polylysine dendrimers improves absorption and lymphatic targeting following SC administration in rats.

    Science.gov (United States)

    Kaminskas, Lisa M; Kota, Jagannath; McLeod, Victoria M; Kelly, Brian D; Karellas, Peter; Porter, Christopher Jh

    2009-12-03

    Polylysine dendrimers have potential as highly flexible, biodegradable nanoparticular carriers that may also promote lymphatic transport. The current study was undertaken to determine the impact of PEGylation on the absorption and lymphatic transport of polylysine dendrimers modified by surface derivatisation with PEG (200, 570 or 2000Da) or 4-benzene sulphonate following SC or IV dosing. PEGylation led to the PEG(200) derived dendrimer being rapidly and completely absorbed into the blood after SC administration, however only 3% of the administered dose was recovered in pooled thoracic lymph over 30h. Increasing the PEG chain length led to a systematic decrease in absorption into the blood and an enhancement of the proportion recovered in the lymphatics (up to 29% over 30h). For the PEG(570) and PEG(2000) derived dendrimers, indirect access to the lymph via equilibration across the capillary beds also appeared to play a role in lymphatic targeting after both IV and SC dosing. In contrast, the anionic benzene sulphonate-capped dendrimer was not well absorbed from the SC injection site (26% bioavailability) into either the blood or the lymph. The data suggest that PEGylated poly-L-lysine dendrimers are well absorbed from SC injection sites and that the extent of lymphatic transport may be enhanced by increasing the size of the PEGylated dendrimer complex.

  13. Effect of generation on the electronic properties of light-emitting dendrimers

    Science.gov (United States)

    Burn, Paul L.; Halim, Mounir; Pillow, Jonathan N. G.; Samuel, Ifor D. W.

    1999-12-01

    We have compared the optical and electronic properties of a series of porphyrin centered dendrimers containing stilbene dendrons. The first and second generation dendrimers could be spin-coated from solution to form good quality thin films. Incorporation into single layer light-emitting diodes gave red-light emission with maximum external quantum efficiencies of 0.02% and 0.04% for the first and second generation dendrimers respectively. We have determined by photoluminescence studies that energy can be transferred efficiently from the stilbene dendrons to the porphyrin core and that PL emission is from the core. Cyclic voltammetry studies on the dendrimers show that the reductions are porphyrin centered with the dendrons only affecting the rate of heterogeneous electron transfer between the electrode and the dendrimers. This suggests that charge mobility within a dendrimer film in an LED will be affected by the porphyrin edge to porphyrin edge distance. We have studied the hydrodynamic radii of the dendrimers by gel permeation chromatography and found as expected that the average porphyrin edge to dendron edge distance increases with generation. This is consistent with the slowing of heterogeneous electron transfer observed in the cyclic voltammetry on increasing the generation number and suggests that the dendrons are interleaved in the solid state to facilitate charge transport.

  14. Transepithelial transport of PAMAM dendrimers across isolated rat jejunal mucosae in ussing chambers.

    Science.gov (United States)

    Hubbard, Dallin; Ghandehari, Hamidreza; Brayden, David J

    2014-08-11

    Oral delivery remains a challenge for poorly permeable hydrophilic macromolecules. Poly(amido amine) (PAMAM) dendrimers have shown potential for their possible oral delivery. Transepithelial transport of carboxyl-terminated G3.5 and amine-terminated G4 PAMAM dendrimers was assessed using isolated rat jejunal mucosae mounted in Ussing chambers. The 1 mM FITC-labeled dendrimers were added to the apical side of mucosae. Apparent permeability coefficients (Papp) from the apical to the basolateral side were significantly increased for FITC when conjugated to G3.5 PAMAM dendrimer compared to FITC alone. Minimal signs of toxicity were observed when mucosae were exposed to both dendrimers with respect to transepithelial electrical resistance changes, carbachol-induced short circuit current stimulation, and histological changes. [(14)C]-mannitol fluxes were not altered in the presence of 1 mM dendrimers, suggesting that the paracellular pathway was not affected at this concentration in this model. These results give insight into the mechanism of PAMAM dendrimer transepithelial rat jejunal transport, as well as toxicological considerations important for oral drug delivery.

  15. Cholesterol-conjugated supramolecular assemblies of low generations polyamidoamine dendrimers for enhanced EGFP plasmid DNA transfection

    Energy Technology Data Exchange (ETDEWEB)

    Golkar, Nasim; Samani, Soliman Mohammadi; Tamaddon, Ali Mohammad, E-mail: amtamadon@gmail.com [Shiraz University of Medical Sciences, Department of Pharmaceutics, School of Pharmacy (Iran, Islamic Republic of)

    2016-05-15

    Aimed to prepare an enhanced gene delivery system with low cytotoxicity and high transfection efficiency, various cholesterol-conjugated derivates of low generation polyamidoamine (PAMAM) dendrimers were prepared. The conjugates were characterized by TNBS assay, FTIR, and {sup 1}H-NMR spectroscopy. Self-assembly of the dendrimer conjugates (G1-Chol, G2-Chol, and G3-Chol) was investigated by pyrene assay. Following formation of the complexes between enhanced green fluorescence protein plasmid and the dendrimer conjugates at various N (primary amine)/P (phosphate) mole ratios, plasmid condensation, biologic stability, cytotoxicity, and protein expression were investigated. The conjugates self-assembled into micellar dispersions with the critical micelle concentration values (<50 µg/ml) depending on the dendrimer generation and cholesterol/amine mole ratio. Cholesterol conjugation resulted in higher resistance of the condensed plasmid DNA in a competition assay with heparin sulfate. Also, the transfection efficiency was determined higher for the cholesterol conjugates than unmodified dendrimers in HepG2 cells, showing the highest for G2-Chol at 40 % degree of cholesterol modification (G2-Chol{sub 40 %}) among various dendrimer generations. Interestingly, such conjugate showed a complete protection of plasmid against serum nucleases. Our results confirmed that the cholesterol conjugation to PAMAM dendrimers of low generations bearing little cytotoxicity improves their several physicochemical and biological characteristics required for an enhanced delivery of plasmid DNA into cells.

  16. Phosphorus Dendrimers as Carriers of siRNA—Characterisation of Dendriplexes

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Majoral

    2013-04-01

    Full Text Available There are many types of dendrimers used as nanomolecules for gene delivery but there is still an ongoing search for ones that are able to effectively deliver drugs to cells. The possibility of gene silencing using siRNA gives hope for effective treatment of numerous diseases. The aim of this work was to investigate in vitro biophysical properties of dendriplexes formed by siRNA and cationic phosphorus dendrimers of 3rd and 4th generation. First, using the ethidium bromide intercalation method, it was examined whether dendrimers have an ability to form complexes with siRNA. Next, the characterisation of dendriplexes formed at different molar ratios was carried out using biophysical methods. The effects of zeta potential, size and changes of siRNA conformation on the complexation with dendrimers were examined. It was found that both phosphorus dendrimers interacted with siRNA. The zeta potential values of dendriplexes ranged from negative to positive and the hydrodynamic diameter depended on the number of dendrimer molecules in the complex. Furthermore, using circular dichroism spectroscopy it was found that cationic phosphorus dendrimers changed only slightly the shape of siRNA CD spectra, thus they did not induce significant changes in the nucleic acid secondary structure during complex formation.

  17. Molecular recognition: Comparative study of a tunable host-guest system by using a fluorescent model system and collision-induced dissociation mass spectrometry on dendrimers

    DEFF Research Database (Denmark)

    Pittelkow, M.; Nielsen, C.B.; Broeren, A.C.

    2005-01-01

    Host-guest interactions between the periphery of adamantylurea-functionalized dendrimers (host) and ureido acetic acid derivatives (guest) were shown to be specific, strong and spatially well-defined. The binding becomes stronger when using phosphonic or sulfonic acid derivatives. In the present...... work we have quantified the binding constants for the host-guest interactions between two different host motifs and six different guest molecules. The host molecules, which resemble the periphery of a poly(propylene imine) dendrimer, have been fitted with an anthracene-based fluorescent probe. The two...... host motifs differ in terms of the length of the spacer between a tertiary amine and two ureido functionalities. The guest molecules all contain an acidic moiety (either a carboxylic acid, a phosphonic acid, or a sulfonic acid) and three of them also contain an ureido moiety capable of forming multiple...

  18. The Debye light scattering equation’s scaling relation reveals the purity of synthetic dendrimers

    Energy Technology Data Exchange (ETDEWEB)

    Tseng, Hui-Yu; Chen, Hsiao-Ping [National Chung Cheng University, Department of Chemistry and Biochemistry (China); Tang, Yi-Hsuan [Kaohsiung Medical University, Department of Medicinal and Applied Chemistry (China); Chen, Hui-Ting [Kaohsiung Medical University, Department of Fragrance and Cosmetic Science (China); Kao, Chai-Lin, E-mail: clkao@kmu.edu.tw [Kaohsiung Medical University, Department of Medicinal and Applied Chemistry (China); Wang, Shau-Chun, E-mail: chescw@ccu.edu.tw [National Chung Cheng University, Department of Chemistry and Biochemistry (China)

    2016-03-15

    Spherical dendrimer structures cannot be structurally modeled using conventional polymer models of random coil or rod-like configurations during the calibration of the static light scattering (LS) detectors used to determine the molecular weight (M.W.) of a dendrimer or directly assess the purity of a synthetic compound. In this paper, we used the Debye equation-based scaling relation, which predicts that the static LS intensity per unit concentration is linearly proportional to the M.W. of a synthetic dendrimer in a dilute solution, as a tool to examine the purity of high-generational compounds and to monitor the progress of dendrimer preparations. Without using expensive equipment, such as nuclear magnetic resonance or mass spectrometry, this method only required an affordable flow injection set-up with an LS detector. Solutions of the purified dendrimers, including the poly(amidoamine) (PAMAM) dendrimer and its fourth to seventh generation pyridine derivatives with size range of 5–9 nm, were used to establish the scaling relation with high linearity. The use of artificially impure mixtures of six or seven generations revealed significant deviations from linearity. The raw synthesized products of the pyridine-modified PAMAM dendrimer, which included incompletely reacted dendrimers, were also examined to gauge the reaction progress. As a reaction toward a particular generational derivative of the PAMAM dendrimers proceeded over time, deviations from the linear scaling relation decreased. The difference between the polydispersity index of the incompletely converted products and that of the pure compounds was only about 0.01. The use of the Debye equation-based scaling relation, therefore, is much more useful than the polydispersity index for monitoring conversion processes toward an indicated functionality number in a given preparation.Graphical abstract.

  19. The Debye light scattering equation’s scaling relation reveals the purity of synthetic dendrimers

    International Nuclear Information System (INIS)

    Tseng, Hui-Yu; Chen, Hsiao-Ping; Tang, Yi-Hsuan; Chen, Hui-Ting; Kao, Chai-Lin; Wang, Shau-Chun

    2016-01-01

    Spherical dendrimer structures cannot be structurally modeled using conventional polymer models of random coil or rod-like configurations during the calibration of the static light scattering (LS) detectors used to determine the molecular weight (M.W.) of a dendrimer or directly assess the purity of a synthetic compound. In this paper, we used the Debye equation-based scaling relation, which predicts that the static LS intensity per unit concentration is linearly proportional to the M.W. of a synthetic dendrimer in a dilute solution, as a tool to examine the purity of high-generational compounds and to monitor the progress of dendrimer preparations. Without using expensive equipment, such as nuclear magnetic resonance or mass spectrometry, this method only required an affordable flow injection set-up with an LS detector. Solutions of the purified dendrimers, including the poly(amidoamine) (PAMAM) dendrimer and its fourth to seventh generation pyridine derivatives with size range of 5–9 nm, were used to establish the scaling relation with high linearity. The use of artificially impure mixtures of six or seven generations revealed significant deviations from linearity. The raw synthesized products of the pyridine-modified PAMAM dendrimer, which included incompletely reacted dendrimers, were also examined to gauge the reaction progress. As a reaction toward a particular generational derivative of the PAMAM dendrimers proceeded over time, deviations from the linear scaling relation decreased. The difference between the polydispersity index of the incompletely converted products and that of the pure compounds was only about 0.01. The use of the Debye equation-based scaling relation, therefore, is much more useful than the polydispersity index for monitoring conversion processes toward an indicated functionality number in a given preparation.Graphical abstract

  20. Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Narsireddy A

    2015-11-01

    Full Text Available Amreddy Narsireddy,1 Kurra Vijayashree,2 Mahesh G Adimoolam,1 Sunkara V Manorama,1 Nalam M Rao21CSIR – Indian Institute of Chemical Technology, 2CSIR – Centre for Cellular and Molecular Biology, Hyderabad, IndiaAbstract: Challenges in photodynamic therapy (PDT include development of efficient near infrared-sensitive photosensitizers (5,10,15,20-tetrakis(4-hydroxyphenyl-21H,23H-porphine [PS] and targeted delivery of PS to the tumor tissue. In this study, a dual functional dendrimer was synthesized for targeted PDT. For targeting, a poly(amidoamine dendrimer (G4 was conjugated with a PS and a nitrilotriacetic acid (NTA group. A peptide specific to human epidermal growth factor 2 was expressed in Escherichia coli with a His-tag and was specifically bound to the NTA group on the dendrimer. Reaction conditions were optimized to result in dendrimers with PS and the NTA at a fractional occupancy of 50% and 15%, respectively. The dendrimers were characterized by nuclear magnetic resonance, matrix-assisted laser desorption/ionization, absorbance, and fluorescence spectroscopy. Using PS fluorescence, cell uptake of these particles was confirmed by confocal microscopy and fluorescence-activated cell sorting. PS-dendrimers are more efficient than free PS in PDT-mediated cell death assays in HER2 positive cells, SK-OV-3. Similar effects were absent in HER2 negative cell line, MCF-7. Compared to free PS, the PS-dendrimers have shown significant tumor suppression in a xenograft animal tumor model. Conjugation of a PS with dendrimers and with a targeting agent has enhanced photodynamic therapeutic effects of the PS.Keywords: photodynamic therapy, dendrimers, nanoparticle, targeted delivery, Affibody, xenograft animal model

  1. Synthesis and Characterization of Poly(Amidoamine Dendrimers Encapsulatd 198Au Nanoparticles

    Directory of Open Access Journals (Sweden)

    R. Ritawidya1,2

    2012-12-01

    Full Text Available Brachytherapy or internal radiotherapy is one of many methods used for treatment of cancer. This modality requires an agent with radionuclides that emits  or β particle with a proper energy. 198Au (99% β max = 0.96 MeV and t1/2 = 2.69 days is one of radionuclides that has been considered to be effective for the above-mentioned purpose. The purpose of this research was to synthesis and characterize poly(amidoamine (PAMAM G3.0 dendrimers encapsulated 198Au nanoparticles as a new brachytherapy agent. PAMAM G3.0 dendrimers encapsulated 198Au nanoparticles was successfully synthesized by a bottom-up method using sodium borohydride as a reductor. Purification was then performed by a size exclusion chromatography in order to separate large Au nanoparticles that were formed outside the cavity of PAMAM G3.0 dendrimers. Prior to the synthesis of PAMAM G3.0 dendrimers encapsulated 198Au nanoparticles, the synthetic procedure was first established by using a non-radioactive Au. The PAMAM G3.0 dendrimers encapsulated Au nanoparticles produced was then characterized by using an UV-Vis spectroscopy, a transmission electron microscopy (TEM, particle size analyzer (PSA, and an atomic absorption spectroscopy (AAS. Characterization results revealed that PAMAM G3.0 dendrimers encapsulated Au nanoparticles that were prepared from a reaction mixture of PAMAM G3.0 dendrimers and Au HAuCl4 with mol ratio of 2.8, was found to be a proper formula. It produced PAMAM G3.0 dendrimers encapsulated Au nanoparticles with diameter of 1.743 nm, spheris, uniform and drug loading value of 26.34%. This formula was then used in synthesis using radioactive Au, 198Au. Characterization results of PAMAM G3.0 dendrimers encapsulated 198Au nanoparticles gave a radiochemical purity of 99.4% and zero charge.

  2. Low potential stable glucose detection at dendrimers modified polyaniline nanotubes

    Directory of Open Access Journals (Sweden)

    Alessandra Nogueira Santos

    2010-03-01

    Full Text Available The utilization of nanostructured materials for development of biosensors is a growing field in medical diagnostics. In this work a glucose biosensor based on bioactive polyglycerol (PGLD and chitosan dendrimers (CHD was developed. PGLD and CHD were bioconjugated with the enzyme glucose oxidase (GOx to obtain dendrimers with glucose sensing properties. Polyaniline nanotubes (PANINT´s were used as electron mediator due to their high ability to promote electron-transfer reactions involving GOx. The PGLD-GOx and CHD-GOx were entrapped in PANINT´s during template electrochemical polymerization of aniline. The prepared PGLD-GOx/PANINT´s and CHD-GOx/PANINT´s biosensors exhibit a strong and stable amperometric response to glucose even at a low potential of +100 mV. The based PGLD-GOx/PANINT´s and CHD-GOx/PANINT´s biosensors showed a good performance in glucose concentrations range in human blood. A comparison of the sensitivities to glucose showed that both biosensors have a linearity range between 0.02 and 10 mM, though PGLD-GOx/PANINT´s is more sensitive (10.41 vs. 7.04 nA.mM-1. The difference in the biosensor behavior and the high sensitivity of the PGLD-GOx/PANINT´s may be due to the specific organization of GOx layer at surface of the modifier macromolecule PGLD and their distribution in PANINT´s. The enzyme affinity for the substrate, K Mapp remains quite good after GOx immobilization on PGLD and CHD dendrimers and entrapment of the bioconjugates in PANINT´s.

  3. Optically nonlinear energy transfer in light-harvesting dendrimers

    Science.gov (United States)

    Andrews, David L.; Bradshaw, David S.

    2004-08-01

    Dendrimeric polymers are the subject of intense research activity geared towards their implementation in nanodevice applications such as energy harvesting systems, organic light-emitting diodes, photosensitizers, low-threshold lasers, and quantum logic elements, etc. A recent development in this area has been the construction of dendrimers specifically designed to exhibit novel forms of optical nonlinearity, exploiting the unique properties of these materials at high levels of photon flux. Starting from a thorough treatment of the underlying theory based on the principles of molecular quantum electrodynamics, it is possible to identify and characterize several optically nonlinear mechanisms for directed energy transfer and energy pooling in multichromophore dendrimers. Such mechanisms fall into two classes: first, those where two-photon absorption by individual donors is followed by transfer of the net energy to an acceptor; second, those where the excitation of two electronically distinct but neighboring donor groups is followed by a collective migration of their energy to a suitable acceptor. Each transfer process is subject to minor dissipative losses. In this paper we describe in detail the balance of factors and the constraints that determines the favored mechanism, which include the excitation statistics, structure of the energy levels, laser coherence factors, chromophore selection rules and architecture, possibilities for the formation of delocalized excitons, spectral overlap, and the overall distribution of donors and acceptors. Furthermore, it transpires that quantum interference between different mechanisms can play an important role. Thus, as the relative importance of each mechanism determines the relevant nanophotonic characteristics, the results reported here afford the means for optimizing highly efficient light-harvesting dendrimer devices.

  4. Photoinduced Electron Transfer of PAMAM Dendrimer-Zinc(II) Porphyrin Associates at Polarized Liquid|Liquid Interfaces.

    Science.gov (United States)

    Nagatani, Hirohisa; Sakae, Hiroki; Torikai, Taishi; Sagara, Takamasa; Imura, Hisanori

    2015-06-09

    The heterogeneous photoinduced electron-transfer reaction of the ion associates between NH2-terminated polyamidoamine (PAMAM) dendrimers and 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato zinc(II) (ZnTPPS(4-)) was studied at the polarized water|1,2-dichloroethane (DCE) interface. The positive photocurrent arising from the photoreduction of ZnTPPS(4-) by a lipophilic quencher, decamethylferrocene, in the interfacial region was significantly enhanced by the ion association with the PAMAM dendrimers. The photocurrent response of the dendrimer-ZnTPPS(4-) associates was dependent on the pH condition and on the generation of dendrimer. A few cationic additives such as polyallylamine and n-octyltrimethyammonium were also examined as alternatives to the PAMAM dendrimer, but the magnitude of the photocurrent enhancement was rather small. The high photoreactivity of the dendrimer-ZnTPPS(4-) associates was interpreted mainly as a result of the high interfacial concentration of photoreactive porphyrin units associated stably with the dendrimer which was preferably adsorbed at the polarized water|DCE interface. The photochemical data observed in the second and fourth generation PAMAM dendrimer systems demonstrated that the higher generation dendrimer which can incorporate a porphyrin molecule more completely in the interior is less efficient for the photocurrent enhancement at the interface. These results indicated that the photoreactivity of ionic reactant at a polarized liquid|liquid interface can readily be modified via ion association with the charged dendrimer.

  5. Poly(amido)amine (PAMAM) dendrimer-cisplatin complexes for chemotherapy of cisplatin-resistant ovarian cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Yellepeddi, Venkata Kashyap; Vangara, Kiran Kumar; Palakurthi, Srinath, E-mail: palakurthi@tamhsc.edu [Texas A and M Health Science Center, Irma Lerma Rangel College of Pharmacy (United States)

    2013-09-15

    Dendrimer-cisplatin complexes were prepared using PAMAM dendrimers with terminal -NH{sub 2} and -COOH groups as well as biotin-conjugated dendrimers. Preformulation parameters of dendrimer-cisplatin complexes were studied using differential scanning calorimetry (DSC) and inductively coupled plasma-mass spectrometry (ICP-MS). Cytotoxicity and mechanism of cytotoxicity of dendrimer-cisplatin complexes was investigated in OVCAR-3, SKOV, A2780 and cisplatin-resistant CP70 human ovarian cancer cell lines. The loading of cisplatin in dendrimers was {approx}11 % (w/w). PAMAM G4 dendrimers with amine surface groups (biotinylated and native) have shown 2.5- to 3.0-fold reduction in IC{sub 50} values in ovarian cancer cells when compared with carboxylate surface dendrimers (p < 0.05). A correlation was observed among cytotoxicity of the complexes, cellular uptake, and platinum-DNA adduct formation. Treatment with dendrimer-cisplatin complexes resulted in a 7.0-fold increase (p < 0.05) in expression of apoptotic genes (Bcl2, Bax, p53) and 13.2- to 27.1-fold increase (p < 0.05) in the activity of caspases 3, 8, and 9 in vitro. Results suggest that PAMAM dendrimers can be used as potential carrier for cisplatin chemotherapy of ovarian cancer.

  6. Amplified amperometric aptasensor for selective detection of protein using catalase-functional DNA-PtNPs dendrimer as a synergetic signal amplification label.

    Science.gov (United States)

    Zhang, Juan; Yuan, Yali; biXie, Shun; Chai, Yaqin; Yuan, Ruo

    2014-10-15

    In this work, we present a new strategy to construct an electrochemical aptasensor for sensitive detection of platelet-derived growth factor BB (PDGF-BB) based on the synergetic amplification of a three-dimensional (3D) nanoscale catalase (CAT) enzyme-functional DNA-platinum nanoparticles (PtNPs) dendrimer through autonomous layer-by-layer assembly. Firstly, polyamidoaminedendrimer (PAMAM) with a hyper-branched and three-dimensional structure was served as nanocarriers to coimmobilize a large number of PDGF-BB binding aptamer (PBA II) and ssDNA 1 (S1) to form PBA II-PAMAM-S1 bioconjugate. In the presence of PDGF-BB, the bioconjugate was self-assembled on the electrode by sandwich assay. Following that, the carried S1 propagated a chain reaction of hybridization events between CAT-PtNPs-S1 and CAT-PtNPs-ssDNA 2 (S2) to form a 3D nanoscale CAT-functional PtNPs-DNA dendrimer, which successfully immobilized substantial CAT enzyme and PtNPs with superior catalysis activity. In this process, the formed negatively charged double-helix DNA could cause the intercalation of hexaammineruthenium(III) chloride (RuHex) into the groove via electrostatic interactions. Thus, numerous RuHex redox probes and CAT were decorated inside/outside of the dendrimer. In the presence of H2O2 in electrolytic cell, the synergistic reaction of CAT and PtNPs towards electrocatalysis could further amplify electrochemical signal. Under optimal condition, the CAT-PtNPs-DNA dendrimer-based sensing system presented a linear dependence between the reduction peak currents and logarithm of PDGF-BB concentrations in the range of 0.00005-35 nM with a relatively low detection limit of 0.02 pM. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. The Janus Face of PAMAM Dendrimers Used to Potentially Cure Nonenzymatic Modifications of Biomacromolecules in Metabolic Disorders—A Critical Review of the Pros and Cons

    Directory of Open Access Journals (Sweden)

    Cezary Watala

    2013-11-01

    Full Text Available Diabetes mellitus, which is characterised by high blood glucose levels and the burden of various macrovascular and microvascular complications, is a cause of much human suffering across the globe. While the use of exogenous insulin and other medications can control and sometimes prevent various diabetes-associated sequelae, numerous diabetic complications are still commonly encountered in diabetic patients. Therefore, there is a strong need for safe and effective antihyperglycaemic agents that provide an alternative or compounding option for the treatment of diabetes. In recent years, amino-terminated poly(amidoamine (PAMAM dendrimers (G2, G3 and G4 have attracted attention due to their protective value as anti-glycation and anti-carbonylation agents that can be used to limit the nonenzymatic modifications of biomacromolecules. The focus of this review is to present a detailed survey of our own data, as well as of the available literature regarding the toxicity, pharmacological properties and overall usefulness of PAMAM dendrimers. This presentation pays particular and primary attention to their therapeutic use in poorly controlled diabetes and its complications, but also in other conditions, such as Alzheimer’s disease, in which such nonenzymatic modifications may underlie the pathophysiological mechanisms. The impact of dendrimer administration on the overall survival of diabetic animals and on glycosylation, glycoxidation, the brain-blood barrier and cellular bioenergetics are demonstrated. Finally, we critically discuss the potential advantages and disadvantages accompanying the use of PAMAM dendrimers in the treatment of metabolic impairments that occur under conditions of chronic hyperglycaemia.

  8. Synthesis and in-vitro cytotoxicity of dendrimer cytostatic conjugates

    OpenAIRE

    Scutaru, Ana Maria

    2011-01-01

    Bendamustine and melphalan are nitrogen mustard derivatives from the group of alkylating agents and are used for the treatment of various cancers such as chronic lymphocytic leukemia (CLL) or breast cancer. However their use is limited by numerous side effects. Therefore, 1,3,5-tris(3-aminopropyl)benzene (G0) and the G1 analogous 1,3,5-tris[3,5-bis(3-aminopropyl)-N-propylbenzamide]benzene were chosen to synthesize cytostatic-dendrimer conjugates and to achieve ‘tumor targeting' through the EP...

  9. Study of the complexation of oxacillin in 1-(4-Carbomethoxypyrrolidone)-terminated PAMAM dendrimers

    DEFF Research Database (Denmark)

    Hansen, Jon Stefan; Ficker, Mario; Petersen, Johannes Fabritius

    2013-01-01

    The complexation of oxacillin to three generations of 1-(4-carbomethoxypyrrolidone)-terminated PAMAM dendrimers was studied with NMR in CD3OD and CDCl3. The stochiometries, which were determined from Job plots, were found to be both solvent- and generation-dependent. The dissociation constants (Kd......) and Gibbs energies for complexation of oxacillin into the 1-(4-carbomethoxypyrrolidone)-terminated PAMAM dendrimer hosts were determined by (1)H NMR titrations and showed weaker binding of oxacillin upon increasing the size (generation) of the dendrimer....

  10. Polymerization of a divalent/tetravalent metal-storing atom-mimicking dendrimer

    OpenAIRE

    Albrecht, Ken; Hirabayashi, Yuki; Otake, Masaya; Mendori, Shin; Tobari, Yuta; Azuma, Yasuo; Majima, Yutaka; Yamamoto, Kimihisa

    2016-01-01

    The phenylazomethine dendrimer (DPA) has a layer-by-layer electron density gradient that is an analog of the Bohr atom (atom mimicry). In combination with electron pair mimicry, the polymerization of this atom-mimicking dendrimer was achieved. The valency of the mimicked atom was controlled by changing the chemical structure of the dendrimer. By mimicking a divalent atom, a one-dimensional (1D) polymer was obtained, and by using a planar tetravalent atom mimic, a 2D polymer was obtained. Thes...

  11. Enhancement of Muramyldipeptide (MDP) Immunostimulatory Activity by Controlled Multimerization on Dendrimers

    DEFF Research Database (Denmark)

    Sørensen, Nanna Skall; Boas, Ulrik; Heegaard, Peter M. H.

    2011-01-01

    Peptidoglycan is a widespread bacterial PAMP molecule and a powerful initiator of innate immune responses. It consists of repeating units of MDP, which as a monomer is only weakly immunostimulatory. Here, MDP-coupled dendrimers were prepared and investigated for stimulation of pig blood mononuclear...... cells. Compared to monomeric MDP, MDP-dendrimers induced a markedly enhanced production of IL-12 p40, IL-1β and IL-6 and completely down-regulated surface expression of B7 and MHC class II. These results suggest a possible novel strategy based on controlled multimerization of minimal PAMP motifs...... on dendrimers for preparing molecularly defined immunostimulators with predictable bioactivities....

  12. Interactions of Poly(amidoamine) Dendrimers with Human Serum Albumin: Binding Constants and Mechanisms

    OpenAIRE

    Giri, Jyotsnendu; Diallo, Mamadou S.; Simpson, André J.; Liu, Yi; Goddard, William A., III; Kumar, Rajeev; Woods, Gwen C.

    2011-01-01

    The interactions of nanomaterials with plasma proteins have a significant impact on their in vivo transport and fate in biological fluids. This article discusses the binding of human serum albumin (HSA) to poly(amidoamine) [PAMAM] dendrimers. We use protein-coated silica particles to measure the HSA binding constants (K_b) of a homologous series of 19 PAMAM dendrimers in aqueous solutions at physiological pH (7.4) as a function of dendrimer generation, terminal group, and core chemistry. To g...

  13. Characterization of the binding of multivalent ions to modified pluronic micelles by isothermal titration calorimetry and modified conductometry

    NARCIS (Netherlands)

    Nispen, van S.F.G.M.; Custers, J.P.A.; Broeke, van den L.J.P.; Keurentjes, J.T.F.

    2010-01-01

    CAE surfactants (carboxylic acid end-standing triblock copolymers of poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide)) are amphiphiles that are able to bind multivalent cations thermoreversibly; a property that can be used to develop new environmentally friendly separation and ion

  14. Multivalent cyclic RGD ligands: influence of linker lengths on receptor binding

    Energy Technology Data Exchange (ETDEWEB)

    Kubas, Holger; Schaefer, Martin; Bauder-Wuest, Ulrike; Eder, Matthias; Oltmanns, Doerte [Department of Radiopharmaceutical Chemistry, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Haberkorn, Uwe; Mier, Walter [Department of Nuclear Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg (Germany); Eisenhut, Michael, E-mail: m.eisenhut@dkfz.d [Department of Radiopharmaceutical Chemistry, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)

    2010-11-15

    Peptides involving the RGD motive (arginine-glycine-aspartic acid) recognize members of the integrin receptor family. Since the receptors are located mainly on the surface of endothelial cells, structural modifications including multimers of c(RGDfE) were recently found to improve the binding avidity for {alpha}{sub v{beta}3} integrin significantly. The multivalent RGD peptides exhibited rather loose linkages partly including oligo(ethylene glycol) spacers (EG{sub n}) with different chain lengths. Therefore, the dependence of multivalent RGD systems with and without EG{sub n} linkers were investigated on their binding properties to cultured {alpha}{sub v{beta}3} integrin-expressing U87MG cells. Methods: We synthesized a series of di-, tri- and tetravalent rigid scaffolds (terephthalic acid, trimesic acid and adamantane-1,3,5,7-tetracarboxylic acid) conjugated to c(RGDyK) ligands, which were linked contiguously or separated by the oligo(ethylene glycol) spacers. The inhibition constants of these c(RGDyK) derivatives were determined by competition assays with {sup 125}I-labeled echistatin. Results: While c(RGDyK) function is a relative weak competitor against [{sup 125}I]echistatin (K{sub i}, 329{+-}18 nM) for {alpha}{sub v{beta}3} integrin-expressing U87MG cells, RGD dimers improved the competition potency considerably (K{sub i}, 64{+-}23 nM). This effect was even more pronounced with the RGD trimers (K{sub i}, 40{+-}7 nM) and tetramers (K{sub i}, 26{+-}9 nM). The introduction of EG{sub n} spacers and the increase of linker lengths proved to be detrimental since more competitors were needed to compete with [{sup 125}I]echistatin. The EG{sub 6} group, for example, reduced the inhibition constants by 29% (dimer), 57% (trimer) and 97% (tetramer). Conclusion: The binding experiments performed with the three forms of multivalent RGD ligands indicate the weakening of competitive potency against [{sup 125}I]echistatin with the introduction of EG{sub n} spacers. This effect

  15. The complex of PAMAM-OH dendrimer with Angiotensin (1–7) prevented the disuse-induced skeletal muscle atrophy in mice

    Science.gov (United States)

    Márquez-Miranda, Valeria; Abrigo, Johanna; Rivera, Juan Carlos; Araya-Durán, Ingrid; Aravena, Javier; Simon, Felipe; Pacheco, Nicolás; González-Nilo, Fernando Danilo; Cabello-Verrugio, Claudio

    2017-01-01

    Angiotensin (1–7) (Ang-(1–7)) is a bioactive heptapeptide with a short half-life and has beneficial effects in several tissues – among them, skeletal muscle – by preventing muscle atrophy. Dendrimers are promising vehicles for the protection and transport of numerous bioactive molecules. This work explored the use of a neutral, non-cytotoxic hydroxyl-terminated poly(amidoamine) (PAMAM-OH) dendrimer as an Ang-(1–7) carrier. Bioinformatics analysis showed that the Ang-(1–7)-binding capacity of the dendrimer presented a 2:1 molar ratio. Molecular dynamics simulation analysis revealed the capacity of neutral PAMAM-OH to protect Ang-(1–7) and form stable complexes. The peptide coverage ability of the dendrimer was between ~50% and 65%. Furthermore, an electrophoretic mobility shift assay demonstrated that neutral PAMAM-OH effectively bonded peptides. Experimental results showed that the Ang-(1–7)/PAMAM-OH complex, but not Ang-(1–7) alone, had an anti-atrophic effect when administered intraperitoneally, as evaluated by muscle strength, fiber diameter, myofibrillar protein levels, and atrogin-1 and MuRF-1 expressions. The results of the Ang-(1–7)/PAMAM-OH complex being intraperitoneally injected were similar to the results obtained when Ang-(1–7) was systemically administered through mini-osmotic pumps. Together, the results suggest that Ang-(1–7) can be protected for PAMAM-OH when this complex is intraperitoneally injected. Therefore, the Ang-(1–7)/PAMAM-OH complex is an efficient delivery method for Ang-(1–7), since it improves the anti-atrophic activity of this peptide in skeletal muscle. PMID:28331320

  16. The complex of PAMAM-OH dendrimer with Angiotensin (1-7) prevented the disuse-induced skeletal muscle atrophy in mice.

    Science.gov (United States)

    Márquez-Miranda, Valeria; Abrigo, Johanna; Rivera, Juan Carlos; Araya-Durán, Ingrid; Aravena, Javier; Simon, Felipe; Pacheco, Nicolás; González-Nilo, Fernando Danilo; Cabello-Verrugio, Claudio

    2017-01-01

    Angiotensin (1-7) (Ang-(1-7)) is a bioactive heptapeptide with a short half-life and has beneficial effects in several tissues - among them, skeletal muscle - by preventing muscle atrophy. Dendrimers are promising vehicles for the protection and transport of numerous bioactive molecules. This work explored the use of a neutral, non-cytotoxic hydroxyl-terminated poly(amidoamine) (PAMAM-OH) dendrimer as an Ang-(1-7) carrier. Bioinformatics analysis showed that the Ang-(1-7)-binding capacity of the dendrimer presented a 2:1 molar ratio. Molecular dynamics simulation analysis revealed the capacity of neutral PAMAM-OH to protect Ang-(1-7) and form stable complexes. The peptide coverage ability of the dendrimer was between ~50% and 65%. Furthermore, an electrophoretic mobility shift assay demonstrated that neutral PAMAM-OH effectively bonded peptides. Experimental results showed that the Ang-(1-7)/PAMAM-OH complex, but not Ang-(1-7) alone, had an anti-atrophic effect when administered intraperitoneally, as evaluated by muscle strength, fiber diameter, myofibrillar protein levels, and atrogin-1 and MuRF-1 expressions. The results of the Ang-(1-7)/PAMAM-OH complex being intraperitoneally injected were similar to the results obtained when Ang-(1-7) was systemically administered through mini-osmotic pumps. Together, the results suggest that Ang-(1-7) can be protected for PAMAM-OH when this complex is intraperitoneally injected. Therefore, the Ang-(1-7)/PAMAM-OH complex is an efficient delivery method for Ang-(1-7), since it improves the anti-atrophic activity of this peptide in skeletal muscle.

  17. Induction of protective immunity against Eimeria tenella, Eimeria necatrix, Eimeria maxima and Eimeria acervulina infections using multivalent epitope DNA vaccines.

    Science.gov (United States)

    Song, Xiaokai; Ren, Zhe; Yan, Ruofeng; Xu, Lixin; Li, Xiangrui

    2015-06-04

    Avian coccidiosis is mostly caused by mixed infection of several Eimeria species under natural conditions and immunity to avian coccidiosis is largely dependent on T-cell immune response. In this study, 14 T-cell epitope fragments from eight antigens of Eimeria tenella (E. tenella), Eimeria necatrix (E. necatrix), Eimeria maxima (E. maxima) and Eimeria acervulina (E. acervulina) were ligated with pVAX1 producing 14 monovalent DNA vaccines, respectively. Protective immunity of the monovalent DNA vaccines was assessed by in vivo challenge experiments and then four most protective fragments of each species were chosen to construct multivalent epitope DNA vaccines with or without chicken IL-2 as genetic adjuvant. Protective efficacies of the epitope DNA vaccines on chickens against E. tenella, E. necatrix, E. maxima and E. acervulina were evaluated. The results showed that the constructed multivalent epitope DNA vaccines significantly increased body weight gain, alleviated enteric lesions and reduced oocyst output of the infected birds. Especially, the multivalent epitope DNA vaccines of pVAX1-NA4-1-TA4-1-LDH-2-EMCDPK-1 and pVAX1-NA4-1-TA4-1-LDH-2-EMCDPK-1-IL-2 not only significantly increased body weight gain, alleviated enteric lesions and reduced oocyst output of the infected birds, but also resulted in anti-coccidial index (ACI) more than 170 against E. tenella, E. necatrix, E. maxima and E. acervulina, which indicated they could induce protective immunity against E. tenella, E. necatrix, E. maxima and E. acervulina. Our findings suggest the constructed multivalent epitope DNA vaccines are the potential candidate multivalent vaccines against mixed infection of Eimeria. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Study of the interactions of PAMAM-NH2 G4 dendrimer with selected natural amino acids in aqueous solutions

    International Nuclear Information System (INIS)

    Buczkowski, Adam; Palecz, Bartlomiej

    2014-01-01

    Highlights: • Calorimetric titration and dilution calorimetry show strong interactions between PAMAM-NH 2 G4 dendrimer and amino acids. • The more polar the amino acid side chain, the more exothermic the effects of the direct interactions with dendrimer. • Macromolecule of PAMAM-NH 2 G4 dendrimer can coordinate 20 to 40 molecules of amino acid. -- Abstract: The interactions of PAMAM-NH 2 G4 dendrimer with selected natural amino acids (Gly, Ala, Val, Leu, Ile, Phe, Ser, Thr, Met, Asn, Gln, Pro and Trp) in aqueous solutions were measured with the use of the techniques of calorimetric titration and dilution calorimetry. The results of calorimetric measurements show strong interactions between PAMAM-NH 2 G4 dendrimer and amino acids with polar substituents. A macromolecule of PAMAM-NH 2 G4 dendrimer can coordinate 20 to 40 molecules of amino acid

  19. Dendrimer-based Macromolecular MRI Contrast Agents: Characteristics and Application

    Directory of Open Access Journals (Sweden)

    Hisataka Kobayashi

    2003-01-01

    Full Text Available Numerous macromolecular MRI contrast agents prepared employing relatively simple chemistry may be readily available that can provide sufficient enhancement for multiple applications. These agents operate using a ~100-fold lower concentration of gadolinium ions in comparison to the necessary concentration of iodine employed in CT imaging. Herein, we describe some of the general potential directions of macromolecular MRI contrast agents using our recently reported families of dendrimer-based agents as examples. Changes in molecular size altered the route of excretion. Smaller-sized contrast agents less than 60 kDa molecular weight were excreted through the kidney resulting in these agents being potentially suitable as functional renal contrast agents. Hydrophilic and larger-sized contrast agents were found better suited for use as blood pool contrast agents. Hydrophobic variants formed with polypropylenimine diaminobutane dendrimer cores created liver contrast agents. Larger hydrophilic agents are useful for lymphatic imaging. Finally, contrast agents conjugated with either monoclonal antibodies or with avidin are able to function as tumor-specific contrast agents, which also might be employed as therapeutic drugs for either gadolinium neutron capture therapy or in conjunction with radioimmunotherapy.

  20. Synthetic Strategies towards Fullerene-Rich Dendrimer Assemblies

    Directory of Open Access Journals (Sweden)

    Jean-François Nierengarten

    2012-02-01

    Full Text Available The sphere-shaped fullerene has attracted considerable interest not least due to the peculiar electronic properties of this carbon allotrope and the fascinating materials emanating from fullerene-derived structures. The rapid development and tremendous advances in organic chemistry allow nowadays the modification of C60 to a great extent by pure chemical means. It is therefore not surprising that the fullerene moiety has also been part of dendrimers. At the initial stage, fullerenes have been examined at the center of the dendritic structure mainly aimed at possible shielding effects as exerted by the dendritic environment and light-harvesting effects due to multiple chromophores located at the periphery of the dendrimer. In recent years, also many research efforts have been devoted towards fullerene-rich nanohybrids containing multiple C60 units in the branches and/or as surface functional groups. In this review, synthetic efforts towards the construction of dendritic fullerene-rich nanostructures have been compiled and will be summarized herein.

  1. Direct Synthesis and Morphological Characterization of Gold-Dendrimer Nanocomposites Prepared Using PAMAM Succinamic Acid Dendrimers: Preliminary Study of the Calcification Potential

    Directory of Open Access Journals (Sweden)

    E. Vasile

    2014-01-01

    Full Text Available Gold-dendrimer nanocomposites were obtained for the first time by a simple colloidal approach based on the use of polyamidoamine dendrimers with succinamic acid terminal groups and dodecanediamine core. Spherical and highly crystalline nanoparticles with dimensions between 3 nm and 60 nm, and size-polydispersity depending on the synthesis conditions, have been generated. The influence of the stoichiometric ratio and the structural and architectural features of the dendrimers on the properties of the nanocomposites has been described. The self-assembling behaviour of these materials produces gold-dendrimer nanostructured porous networks with variable density, porosity, and composition. The investigations of the reaction systems, by TEM, at two postsynthesis moments, allowed to preliminary establish the control over the properties of the nanocomposite products. Furthermore, this study allowed better understanding of the mechanism of nanocomposite generation. Impressively, in the early stages of the synthesis, the organization of gold inside the dendrimer molecules has been evidenced by micrographs. Growth and ripening mechanisms further lead to nanoparticles with typical characteristics. The potential of such nanocomposite particles to induce calcification when coating a polymer substrate was also investigated.

  2. Direct synthesis and morphological characterization of gold-dendrimer nanocomposites prepared using PAMAM succinamic acid dendrimers: preliminary study of the calcification potential.

    Science.gov (United States)

    Vasile, E; Serafim, A; Petre, D; Giol, D; Dubruel, P; Iovu, H; Stancu, I C

    2014-01-01

    Gold-dendrimer nanocomposites were obtained for the first time by a simple colloidal approach based on the use of polyamidoamine dendrimers with succinamic acid terminal groups and dodecanediamine core. Spherical and highly crystalline nanoparticles with dimensions between 3 nm and 60 nm, and size-polydispersity depending on the synthesis conditions, have been generated. The influence of the stoichiometric ratio and the structural and architectural features of the dendrimers on the properties of the nanocomposites has been described. The self-assembling behaviour of these materials produces gold-dendrimer nanostructured porous networks with variable density, porosity, and composition. The investigations of the reaction systems, by TEM, at two postsynthesis moments, allowed to preliminary establish the control over the properties of the nanocomposite products. Furthermore, this study allowed better understanding of the mechanism of nanocomposite generation. Impressively, in the early stages of the synthesis, the organization of gold inside the dendrimer molecules has been evidenced by micrographs. Growth and ripening mechanisms further lead to nanoparticles with typical characteristics. The potential of such nanocomposite particles to induce calcification when coating a polymer substrate was also investigated.

  3. Unusual concentration-dependent microscopic dynamics of dendrimers in aqueous solution

    International Nuclear Information System (INIS)

    Wong, Kaikin; Wu, Chin Ming; Lam, Hak Fai; Chathoth, Suresh M.

    2016-01-01

    Dendrimers are novel three-dimensional, hyperbranched globular nanopolymeric macromolecules. The nanoscopic size, narrow polydispersity index, excellent control over molecular structure, availability of multiple functional groups at the periphery, and cavities in the interior made them very attractive candidate for drug delivery. In this communication, we have studied the microscopic dynamics of tetra-acid and pentaerythritol glycidyl ether dendrimers dissolved in aqueous solution with different concentrations. The effects of concentration and temperature to their long-range diffusion process are investigated by dynamic light scattering. Experimental results show a huge variation in the translational diffusion coefficient for the two dendrimers samples. Besides, the dependence of diffusion coefficients on concentration is unusually different in these dendrimer samples. Although the diffusion process follows Arrhenius relation with the temperature in both systems, the activation energy for the diffusion process has a distinct concentration dependence.

  4. Unusual concentration-dependent microscopic dynamics of dendrimers in aqueous solution

    Science.gov (United States)

    Wong, Kaikin; Wu, Chin Ming; Lam, Hak Fai; Chathoth, Suresh M.

    2016-05-01

    Dendrimers are novel three-dimensional, hyperbranched globular nanopolymeric macromolecules. The nanoscopic size, narrow polydispersity index, excellent control over molecular structure, availability of multiple functional groups at the periphery, and cavities in the interior made them very attractive candidate for drug delivery. In this communication, we have studied the microscopic dynamics of tetra-acid and pentaerythritol glycidyl ether dendrimers dissolved in aqueous solution with different concentrations. The effects of concentration and temperature to their long-range diffusion process are investigated by dynamic light scattering. Experimental results show a huge variation in the translational diffusion coefficient for the two dendrimers samples. Besides, the dependence of diffusion coefficients on concentration is unusually different in these dendrimer samples. Although the diffusion process follows Arrhenius relation with the temperature in both systems, the activation energy for the diffusion process has a distinct concentration dependence.

  5. Effect of viologen-phosphorus dendrimers on acetylcholinesterase and butyrylcholinesterase activities.

    Science.gov (United States)

    Ciepluch, Karol; Weber, Monika; Katir, Nadia; Caminade, Anne-Marie; El Kadib, Abdelkrim; Klajnert, Barbara; Majoral, Jean Pierre; Bryszewska, Maria

    2013-03-01

    The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is the first step in checking whether new compounds can be considered as drugs for treating neurodegenerative diseases. The effect of viologen-phosphorus dendrimers on AChE and BChE activities was studied. The results show that the effects on the cholinesterase activities depend on dendrimer type and size. Viologen dendrimers can interact with the enzymes in two ways: they can bind either to a peripheral site of the enzyme or to amino acids located near the active site, inhibiting catalysis by both cholinesterases. All tested non-toxic viologen-phosphorus dendrimers inhibited the activities of both cholinesterases, showing their potential as new drugs for treating neurodegenerative diseases. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Unusual concentration-dependent microscopic dynamics of dendrimers in aqueous solution

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Kaikin; Wu, Chin Ming; Lam, Hak Fai; Chathoth, Suresh M., E-mail: smavilac@cityu.edu.hk [City University of Hong Kong, Department of Physics and Materials Science (Hong Kong, People’s Republic of China) (China)

    2016-05-15

    Dendrimers are novel three-dimensional, hyperbranched globular nanopolymeric macromolecules. The nanoscopic size, narrow polydispersity index, excellent control over molecular structure, availability of multiple functional groups at the periphery, and cavities in the interior made them very attractive candidate for drug delivery. In this communication, we have studied the microscopic dynamics of tetra-acid and pentaerythritol glycidyl ether dendrimers dissolved in aqueous solution with different concentrations. The effects of concentration and temperature to their long-range diffusion process are investigated by dynamic light scattering. Experimental results show a huge variation in the translational diffusion coefficient for the two dendrimers samples. Besides, the dependence of diffusion coefficients on concentration is unusually different in these dendrimer samples. Although the diffusion process follows Arrhenius relation with the temperature in both systems, the activation energy for the diffusion process has a distinct concentration dependence.

  7. Brain Targeting of a Water Insoluble Antipsychotic Drug Haloperidol via the Intranasal Route Using PAMAM Dendrimer.

    Science.gov (United States)

    Katare, Yogesh K; Daya, Ritesh P; Sookram Gray, Christal; Luckham, Roger E; Bhandari, Jayant; Chauhan, Abhay S; Mishra, Ram K

    2015-09-08

    Delivery of therapeutics to the brain is challenging because many organic molecules have inadequate aqueous solubility and limited bioavailability. We investigated the efficiency of a dendrimer-based formulation of a poorly aqueous soluble drug, haloperidol, in targeting the brain via intranasal and intraperitoneal administration. Aqueous solubility of haloperidol was increased by more than 100-fold in the developed formulation. Formulation was assessed via different routes of administration for behavioral (cataleptic and locomotor) responses, and for haloperidol distribution in plasma and brain tissues. Dendrimer-based formulation showed significantly higher distribution of haloperidol in the brain and plasma compared to a control formulation of haloperidol administered via intraperitoneal injection. Additionally, 6.7 times lower doses of the dendrimer-haloperidol formulation administered via the intranasal route produced behavioral responses that were comparable to those induced by haloperidol formulations administered via intraperitoneal injection. This study demonstrates the potential of dendrimer in improving the delivery of water insoluble drugs to brain.

  8. Synthesis of Dendrimer Containing Dialkylated-fluorene Unit as a Core Chromophore via Click Chemistry

    International Nuclear Information System (INIS)

    Han, Seung Choul; Lee, Jae Wook; Jin, Sung Ho

    2012-01-01

    The convergent synthetic strategy for the emissive dendrimers having the chromophore at core via the coppercatalyzed 1,3-dipolar cycloaddition reaction between alkyne and azide was described. 2,7-Diazido-9,9-dioctyl- 9H-fluorene, designed to serve as the core in dendrimer, was stitched with the alkyne-functionalized Frechettype and PAMAM dendrons by the click chemistry leading to the formation of the corresponding fluorescent dendrimers in high yields. The preliminary photoluminescence studies indicated that 2,7-diazido-9,9-dioctyl- 9H-fluorene showed no fluorescence due to the quenching effect from the electron-rich α-nitrogen of the azido group but the dendrimers fluoresced due to the elimination of the quenching through the formation of the triazole ring

  9. Dendrimers as tunable vectors of drug delivery systems and biomedical and ocular applications

    Science.gov (United States)

    Kalomiraki, Marina; Thermos, Kyriaki; Chaniotakis, Nikos A

    2016-01-01

    Dendrimers are large polymeric structures with nanosize dimensions (1–10 nm) and unique physicochemical properties. The major advantage of dendrimers compared with linear polymers is their spherical-shaped structure. During synthesis, the size and shape of the dendrimer can be customized and controlled, so the finished macromolecule will have a specific “architecture” and terminal groups. These characteristics will determine its suitability for drug delivery, diagnostic imaging, and as a genetic material carrier. This review will focus initially on the unique properties of dendrimers and their use in biomedical applications, as antibacterial, antitumor, and diagnostic agents. Subsequently, emphasis will be given to their use in drug delivery for ocular diseases. PMID:26730187

  10. Kinetic and thermodynamic study of the transfer of anionic polyamidoamine dendrimers across two immiscible liquids

    International Nuclear Information System (INIS)

    Gonzalez-Fuentes, Miguel A.; Manriquez, J.; Antano-Lopez, R.; Godinez, Luis A.

    2011-01-01

    The kinetics and thermodynamics for the phase transfer of carboxyl-terminated polyamidoamine (PAMAM) dendrimers across the water/dichloroethane interface were analyzed by cyclic voltammetry and electrochemical impedance spectroscopy. A three phase junction was employed by inserting a cylindrical gold electrode through the liquid-liquid interface. The reversible redox species decamethylferrocene (DMFc) was used in the organic phase in order to promote dendrimer transfer. It was found that the electrochemical behaviour of DMFc at the gold/dichloroethane interface depends on the generation and concentration of the dendrimer species in the aqueous phase. In addition, it was observed that the electrochemically driven transfer of these macromolecules corresponds to a quasi-reversible process. The data obtained from thermodynamic studies indicate that dendrimers are transferred between the two phases under study by an entropy controlled process.

  11. Dendrimers as tunable vectors of drug delivery systems and biomedical and ocular applications

    Directory of Open Access Journals (Sweden)

    Kalomiraki M

    2015-12-01

    Full Text Available Marina Kalomiraki,1 Kyriaki Thermos,2 Nikos A Chaniotakis1 1Laboratory of Analytical Chemistry, Department of Chemistry, 2Department of Pharmacology, School of Medicine, University of Crete Voutes, Heraklion, Greece Abstract: Dendrimers are large polymeric structures with nanosize dimensions (1–10 nm and unique physicochemical properties. The major advantage of dendrimers compared with linear polymers is their spherical-shaped structure. During synthesis, the size and shape of the dendrimer can be customized and controlled, so the finished macromolecule will have a specific “architecture” and terminal groups. These characteristics will determine its suitability for drug delivery, diagnostic imaging, and as a genetic material carrier. This review will focus initially on the unique properties of dendrimers and their use in biomedical applications, as antibacterial, antitumor, and diagnostic agents. Subsequently, emphasis will be given to their use in drug delivery for ocular diseases. Keywords: nanoparticles, ocular diseases, encapsulation, macromolecule, diagnostic agent

  12. Iodine-Containing Mass-Defect-Tuned Dendrimers for Use as Internal Mass Spectrometry Calibrants

    Science.gov (United States)

    Giesen, Joseph A.; Diament, Benjamin J.; Grayson, Scott M.

    2018-03-01

    Calibrants based on synthetic dendrimers have been recently proposed as a versatile alternative to peptides and proteins for both MALDI and ESI mass spectrometry calibration. Because of their modular synthetic platform, dendrimer calibrants are particularly amenable to tailoring for specific applications. Utilizing this versatility, a set of dendrimers has been designed as an internal calibrant with a tailored mass defect to differentiate them from the majority of natural peptide analytes. This was achieved by incorporating a tris-iodinated aromatic core as an initiator for the dendrimer synthesis, thereby affording multiple calibration points ( m/z range 600-2300) with an optimized mass-defect offset relative to all peptides composed of the 20 most common proteinogenic amino acids. [Figure not available: see fulltext.

  13. Effect of methotrexate conjugated PAMAM dendrimers on the viability of MES-SA uterine cancer cells

    Directory of Open Access Journals (Sweden)

    Samreen Khatri

    2014-01-01

    Full Text Available The aim of this work was to synthesize methotrexate (MTX-polyamidoamine (PAMAM dendritic nanoconjugates and to study their effect on cell viability in uterine sarcoma cells. The amide-bonded PAMAM dendrimer-MTX conjugates were prepared by conjugation between the amine-terminated G5 dendrimer and the carboxylic groups of the MTX using a dicyclohexylcarbodiimide coupling reaction. The formation of conjugates was evaluated by ultraviolet (UV and 1 H nuclear magnetic resonance ( 1 H NMR spectroscopy studies. The cell survival of MES-SA cells, a uterine sarcoma cell line, was evaluated in the presence of the dendrimer-MTX nanoconjugate, using appropriate controls. The UV and 1 H NMR study confirmed the formation of covalent bonds between the drug and the dendrimer. The cell viability study indicated that the nanoconjugates had significantly improved cell killing compared to the free MTX.

  14. Interactive transport of guanidinylated poly(propylene imine)-based dendrimers through liposomal and cellular membranes.

    Science.gov (United States)

    Tsogas, Ioannis; Sideratou, Zili; Tsiourvas, Dimitris; Theodossiou, Theodossis A; Paleos, Constantinos M

    2007-10-15

    The ability of guanidinylated poly(propylene imine) dendrimers to translocate across lipid bilayers was assessed by employing either a model phosphate-bearing liposomal membrane system or A549 human lung carcinoma cells. Two dendrimer generations, differing in the number of surface guanidinium groups, were employed, while surface acetylation or the use of spacers affected the binding of the guanidinium group to the phosphate moiety and finally the transport efficiency. Following adhesion of dendrimers with liposomes, fusion or transport occurred. Transport through the liposomal bilayer was observed at low guanidinium/phosphate molar ratios, and was enhanced when the bilayer was in the liquid-crystalline phase. For effective transport through the liposomal membrane, an optimum balance between the binding strength and the degree of hydrophobicity of the guanidinylated dendrimer is required. In experiments performed in vitro with cells, efficient penetration and internalization in subcellular organelles and cytosol was observed.

  15. Phosphorus-Based Dendrimer ABP Treats Neuroinflammation by Promoting IL-10-Producing CD4(+) T Cells.

    Science.gov (United States)

    Hayder, Myriam; Varilh, Marjorie; Turrin, Cédric-Olivier; Saoudi, Abdelhadi; Caminade, Anne-Marie; Poupot, Rémy; Liblau, Roland S

    2015-11-09

    Dendrimers are polyfunctional nano-objects of perfectly defined structure that can provide innovative alternatives for the treatment of chronic inflammatory diseases, including multiple sclerosis (MS). To investigate the efficiency of a recently described amino-bis(methylene phosphonate)-capped ABP dendrimer as a potential drug candidate for MS, we used the classical mouse model of MOG35-55-induced experimental autoimmune encephalomyelitis (EAE). Our study provides evidence that the ABP dendrimer prevents the development of EAE and inhibits the progression of established disease with a comparable therapeutic benefit as the approved treatment Fingolimod. We also show that the ABP dendrimer redirects the pathogenic myelin-specific CD4(+) T cell response toward IL-10 production.

  16. Molecular dynamics study of the structure and interparticle interactions of polyethylene glycol-conjugated PAMAM dendrimers.

    Science.gov (United States)

    Lee, Hwankyu; Larson, Ronald G

    2009-10-08

    We performed molecular dynamics (MD) simulations of one or two copies of polyethylene glycol of molecular weight 550 (PEG550) and 5000 (PEG5000) daltons, conjugated to generation 3 (G3) to 5 (G5) polyamidoamine (PAMAM) dendrimers with explicit water using a coarse-grained model. We found the radii of gyration of these dendrimer-PEG molecules to be close to those measured in experiments by Hedden and Bauer (Hedden , R. C. ; Bauer , B. J. Macromolecules 2003 , 36 , 1829.). Densely grafted PEG ligands (>50% of the dendrimer surface) extend like brushes, with layer thickness in agreement with theory for starlike polymers. Two dendrimer-PEG complexes in the box drift away from each other, indicating that no aggregation is induced by either short or long PEG chains, conflicting with a recent view that the cytotoxicity of some PEGylated particles might be due to particle aggregation for long PEG lengths.

  17. Multivalent display of proteins on viral nanoparticles using molecular recognition and chemical ligation strategies

    Science.gov (United States)

    Venter, P. Arno; Dirksen, Anouk; Thomas, Diane; Manchester, Marianne; Dawson, Philip E.; Schneemann, Anette

    2011-01-01

    Multivalent display of heterologous proteins on viral nanoparticles forms a basis for numerous applications in nanotechnology, including vaccine development, targeted therapeutic delivery and tissue-specific bio-imaging. In many instances, precise placement of proteins is required for optimal functioning of the supramolecular assemblies, but orientation- and site-specific coupling of proteins to viral scaffolds remains a significant technical challenge. We have developed two strategies that allow for controlled attachment of a variety of proteins on viral particles using covalent and noncovalent principles. In one strategy, an interaction between domain 4 of anthrax protective antigen and its receptor was used to display multiple copies of a target protein on virus-like particles. In the other, expressed protein ligation and aniline-catalyzed oximation was used to covalently display a model protein. The latter strategy, in particular, yielded nanoparticles that induced potent immune responses to the coupled protein, suggesting potential applications in vaccine development. PMID:21545187

  18. Multivalent-Counterion-Induced Surfactant Multilayer Formation at Hydrophobic and Hydrophilic Solid-Solution Interfaces.

    Science.gov (United States)

    Penfold, Jeffrey; Thomas, Robert K; Li, Peixun; Xu, Hui; Tucker, Ian M; Petkov, Jordan T; Sivia, Devinderjit S

    2015-06-23

    Surface multilayer formation from the anionic-nonionic surfactant mixture of sodium dodecyl dioxyethylene sulfate, SLES, and monododecyl dodecaethylene glycol, C12E12, by the addition of multivalent Al(3+) counterions at the solid-solution interface is observed and characterized by neutron reflectivity, NR. The ability to form surface multilayer structures on hydrophobic and hydrophilic silica and cellulose surfaces is demonstrated. The surface multilayer formation is more pronounced and more well developed on the hydrophilic and hydrophobic silica surfaces than on the hydrophilic and hydrophobic cellulose surfaces. The less well developed multilayer formation on the cellulose surfaces is attributed to the greater surface inhomogeneities of the cellulose surface which partially inhibit lateral coherence and growth of the multilayer domains at the surface. The surface multilayer formation is associated with extreme wetting properties and offers the potential for the manipulation of the solid surfaces for enhanced adsorption and control of the wetting behavior.

  19. Orthogonal dual-modification of proteins for the engineering of multivalent protein scaffolds

    Directory of Open Access Journals (Sweden)

    Michaela Mühlberg

    2015-05-01

    Full Text Available To add new tools to the repertoire of protein-based multivalent scaffold design, we have developed a novel dual-labeling strategy for proteins that combines residue-specific incorporation of unnatural amino acids with chemical oxidative aldehyde formation at the N-terminus of a protein. Our approach relies on the selective introduction of two different functional moieties in a protein by mutually orthogonal copper-catalyzed azide–alkyne cycloaddition (CuAAC and oxime ligation. This method was applied to the conjugation of biotin and β-linked galactose residues to yield an enzymatically active thermophilic lipase, which revealed specific binding to Erythrina cristagalli lectin by SPR binding studies.

  20. Development of a Multivalent Subunit Vaccine against Tularemia Using Tobacco Mosaic Virus (TMV Based Delivery System.

    Directory of Open Access Journals (Sweden)

    Sukalyani Banik

    Full Text Available Francisella tularensis is a facultative intracellular pathogen, and is the causative agent of a fatal human disease known as tularemia. F. tularensis is classified as a Category A Biothreat agent by the CDC based on its use in bioweapon programs by several countries in the past and its potential to be used as an agent of bioterrorism. No licensed vaccine is currently available for prevention of tularemia. In this study, we used a novel approach for development of a multivalent subunit vaccine against tularemia by using an efficient tobacco mosaic virus (TMV based delivery platform. The multivalent subunit vaccine was formulated to contain a combination of F. tularensis protective antigens: OmpA-like protein (OmpA, chaperone protein DnaK and lipoprotein Tul4 from the highly virulent F. tularensis SchuS4 strain. Two different vaccine formulations and immunization schedules were used. The immunized mice were challenged with lethal (10xLD100 doses of F. tularensis LVS on day 28 of the primary immunization and observed daily for morbidity and mortality. Results from this study demonstrate that TMV can be used as a carrier for effective delivery of multiple F. tularensis antigens. TMV-conjugate vaccine formulations are safe and multiple doses can be administered without causing any adverse reactions in immunized mice. Immunization with TMV-conjugated F. tularensis proteins induced a strong humoral immune response and protected mice against respiratory challenges with very high doses of F. tularensis LVS. This study provides a proof-of-concept that TMV can serve as a suitable platform for simultaneous delivery of multiple protective antigens of F. tularensis. Refinement of vaccine formulations coupled with TMV-targeting strategies developed in this study will provide a platform for development of an effective tularemia subunit vaccine as well as a vaccination approach that may broadly be applicable to many other bacterial pathogens.

  1. Fate and transformation products of amine-terminated PAMAM dendrimers under ozonation and irradiation

    International Nuclear Information System (INIS)

    Santiago-Morales, Javier; Rosal, Roberto; Hernando, María D.; Ulaszewska, Maria M.; García-Calvo, Eloy; Fernández-Alba, Amadeo R.

    2014-01-01

    Highlights: • We detected transformation products from dendrimer under ozonation and irradiation. • Retro-Michael fragmentation pathway with highly oxygenated structures. • High toxicity of G3 PAMAM dendrimer for green algae. • Reactive oxygen species were associated with the toxic damage. • Transformation mixtures could be more toxic than the parent dendrimer. -- Abstract: This article deals with the degradation of a third-generation (G3) poly(amidoamine) (PAMAM) dendrimer under ozonation and irradiation. The identification and quantification of G3 PAMAM dendrimer and its transformation products has been performed by liquid chromatography–electrospray ionization-hybrid quadrupole time-of-flight-mass spectrometry. The dendrimer was completely depleted by ozone in less than 1 min. The effect of ultraviolet irradiation was attributed to hydroxyl-mediated oxidation. The transformation products were attributed to the oxidation of amines, which resulted in highly oxidized structures with abundance of carboxylic acids, which started from the formation of amine oxide and the scission of the C-N bond of the amide group. We studied the toxicity of treated mixtures for six different organisms: the acute toxicity for the bacterium Vibrio fischeri and the microcrustacean Daphnia magna, the multigenerational growth inhibition of the alga Pseudokirchneriella subcapitata, and the seed germination phytotoxicity of Licopersicon esculentum, Lactuca sativa and Lolium perenne. Ozonation and irradiation originated transformation products are more toxic than the parent dendrimer. The toxicity of the dendrimer for the green alga was linked to a strong increase of intracellular reactive oxygen species with intense lipid peroxidation

  2. Fate and transformation products of amine-terminated PAMAM dendrimers under ozonation and irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Santiago-Morales, Javier [Department of Chemical Engineering, University of Alcalá, 28871 Alcalá de Henares, Madrid (Spain); Rosal, Roberto, E-mail: roberto.rosal@uah.es [Department of Chemical Engineering, University of Alcalá, 28871 Alcalá de Henares, Madrid (Spain); Advanced Study Institute of Madrid, IMDEA Agua, Parque Científico Tecnológico, 28805 Alcalá de Henares, Madrid (Spain); Hernando, María D. [Spanish National Institute for Agricultural and Food Research and Technology – INIA, Crta. de la Coruña, km 7.5, 28040 Madrid (Spain); Ulaszewska, Maria M. [Advanced Study Institute of Madrid, IMDEA Agua, Parque Científico Tecnológico, 28805 Alcalá de Henares, Madrid (Spain); García-Calvo, Eloy [Department of Chemical Engineering, University of Alcalá, 28871 Alcalá de Henares, Madrid (Spain); Advanced Study Institute of Madrid, IMDEA Agua, Parque Científico Tecnológico, 28805 Alcalá de Henares, Madrid (Spain); Fernández-Alba, Amadeo R. [Advanced Study Institute of Madrid, IMDEA Agua, Parque Científico Tecnológico, 28805 Alcalá de Henares, Madrid (Spain); Pesticide Residue Research Group, Department of Hydrogeology and Analytical Chemistry, University of Almería, 04120 Almería (Spain)

    2014-02-15

    Highlights: • We detected transformation products from dendrimer under ozonation and irradiation. • Retro-Michael fragmentation pathway with highly oxygenated structures. • High toxicity of G3 PAMAM dendrimer for green algae. • Reactive oxygen species were associated with the toxic damage. • Transformation mixtures could be more toxic than the parent dendrimer. -- Abstract: This article deals with the degradation of a third-generation (G3) poly(amidoamine) (PAMAM) dendrimer under ozonation and irradiation. The identification and quantification of G3 PAMAM dendrimer and its transformation products has been performed by liquid chromatography–electrospray ionization-hybrid quadrupole time-of-flight-mass spectrometry. The dendrimer was completely depleted by ozone in less than 1 min. The effect of ultraviolet irradiation was attributed to hydroxyl-mediated oxidation. The transformation products were attributed to the oxidation of amines, which resulted in highly oxidized structures with abundance of carboxylic acids, which started from the formation of amine oxide and the scission of the C-N bond of the amide group. We studied the toxicity of treated mixtures for six different organisms: the acute toxicity for the bacterium Vibrio fischeri and the microcrustacean Daphnia magna, the multigenerational growth inhibition of the alga Pseudokirchneriella subcapitata, and the seed germination phytotoxicity of Licopersicon esculentum, Lactuca sativa and Lolium perenne. Ozonation and irradiation originated transformation products are more toxic than the parent dendrimer. The toxicity of the dendrimer for the green alga was linked to a strong increase of intracellular reactive oxygen species with intense lipid peroxidation.

  3. Magnetic properties of dendrimer structures with different coordination numbers: A Monte Carlo study

    Science.gov (United States)

    Masrour, R.; Jabar, A.

    2016-11-01

    We investigate the magnetic properties of Cayley trees of large molecules with dendrimer structure using Monte Carlo simulations. The thermal magnetization and magnetic susceptibility of a dendrimer structure are given with different coordination numbers, Z=3, 4, 5 and different generations g=3 and 2. The variation of magnetizations with the exchange interactions and crystal fields have been given of this system. The magnetic hysteresis cycles have been established.

  4. Synthesis of a cationic thermoresponsive dendrimer and its self-assembly with apoferritin protein cage

    OpenAIRE

    Välimäki, Salla

    2015-01-01

    The aim of this work was to synthesize cationic dendrimer with a thermoresponsive polymer tail and complex the dendrimer with negatively charged apoferritin protein nanocage. These kind of systems are developed, for example, for biomedical applications. Spermine dendron with atom transfer radical polymerization initiator in focal point was synthesized successfully. Thermoresponsive poly(di(ethylene glycol) methyl ether methacrylate) was in situ polymerized to the dendron to form the therm...

  5. Epitaxially Grown Ultra-Flat Self-Assembling Monolayers with Dendrimers

    Directory of Open Access Journals (Sweden)

    Takane Imaoka

    2018-02-01

    Full Text Available Mono-molecular films formed by physical adsorption and dendrimer self-assembly were prepared on various substrate surfaces. It was demonstrated that a uniform dendrimer-based monolayer on the subnanometer scale can be easily constructed via simple dip coating. Furthermore, it was shown that an epitaxially grown monolayer film reflecting the crystal structure of the substrate (highly ordered pyrolytic graphite (HOPG can also be formed by aligning specific conditions.

  6. Charge transport properties of carbazole dendrimers in organic field-effect transistors

    Science.gov (United States)

    Mutkins, Karyn; Chen, Simon S. Y.; Aljada, Muhsen; Powell, Ben J.; Olsen, Seth; Burn, Paul L.; Meredith, Paul

    2011-10-01

    We report three generations of p-type dendrimer semiconductors comprised of spirobifluorene cores, carbazole branching units and fluorene surface groups for use in organic field-effect transistors (OFETs). The group of dendrimers are defined by their generation and noted as SBF-(Gx)2, where x is the generation. Top contact-bottom gate OFETs were fabricated by spin-coating the dendrimers onto an n-octyltrichlorosilane (OTS) passivated silicon dioxide surface. The dendrimer films were found to be amorphous. The highest mobility was measured for the first generation dendrimer (SBF-(G1)2), which had an average mobility of (6.6 +/- 0.2) × 10-5 cm2/V s and an ON/OFF ratio of 3.0 × 104. As the generation of the dendrimer was increased there was only a slight decrease in the measured mobility in spite of the significantly different molecular sizes of the dendrimers. The mobility of SBF-(G3)2, which had a hydrodynamic radius almost twice of SBF-(G1)2, still had an average mobility of (4.7 +/- 0.6) × 10-5 cm2/V s and an ON/OFF ratio of 2.7 × 103. Density functional theory calculations showed that the highest occupied molecular orbital was distributed over the core and carbazole units meaning that both intra- and intermolecular charge transfer could occur enabling the hole mobility to remain essentially constant even though the dendrimers would pack differently in the solid-state.

  7. Targeting human liver cancer cells with lactobionic acid-G(4)-PAMAM-FITC sorafenib loaded dendrimers.

    Science.gov (United States)

    Iacobazzi, Rosa Maria; Porcelli, Letizia; Lopedota, Angela Assunta; Laquintana, Valentino; Lopalco, Antonio; Cutrignelli, Annalisa; Altamura, Emiliano; Di Fonte, Roberta; Azzariti, Amalia; Franco, Massimo; Denora, Nunzio

    2017-08-07

    Reported here is the synthesis and biological evaluation of the asialoglycoprotein receptor (ASGP-R) targeted fourth generation poliamidoamine dendrimer (G(4)-PAMAM) loaded with sorafenib. The ASGP-R targeted dendrimer was obtained by conjugation of Lactobionic acid (La) to the G(4)-PAMAM dendrimer, followed by acetylation (Ac) of the free amino groups in order to reduce the non-specific interactions with the cell membrane. Moreover, by additionally grafting fluorescein (FITC), it was easy to characterize the internalization pathway and the intracellular fate of the targeted dendrimer Ac-La-G(4)-PAMAM-FITC. In vitro experiments performed on HepG-2 and HLE cell lines, allowed to study the ability of the dendrimers to affect the cell vitality. Confocal microscopy and cytofluorimetric analysis confirmed higher binding and uptake ability of the Ac-La-G(4)-PAMAM-FITC dendrimer in well differentiated and ASGP-R expressing human liver cancer cell line HepG-2 compared non-expressing HLE cells. Ac-La-G(4)-PAMAM-FITC dendrimer loaded with sorafenib was stable and showed sustained sorafenib release. As evidenced by the cytotoxicity studies, sorafenib included in the dendrimer maintained its effectiveness, and was able to produce a longer lasting effect over the time compared to molar equivalent doses of free sorafenib. This new targeted dendrimer appears to be a suitable carrier for the delivery of sorafenib to liver cancer cells expressing ASGP-R. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Intracellular Ca2+ release mediates cationic but not anionic poly(amidoamine) (PAMAM) dendrimer-induced tight junction modulation.

    Science.gov (United States)

    Avaritt, Brittany R; Swaan, Peter W

    2014-09-01

    Poly(amidoamine) (PAMAM) dendrimers show great promise for utilization as oral drug delivery vehicles. These polymers are capable of traversing epithelial barriers, and have been shown to translocate by both transcellular and paracellular routes. While many proof-of-concept studies have shown that PAMAM dendrimers improve intestinal transport, little information exists on the mechanisms of paracellular transport, specifically dendrimer-induced tight junction modulation. Using anionic G3.5 and cationic G4 PAMAM dendrimers with known absorption enhancers, we investigated tight junction modulation in Caco-2 monolayers by visualization and mannitol permeability and compared dendrimer-mediated tight junction modulation to that of established permeation enhancers. [(14)C]-Mannitol permeability in the presence and absence of phospholipase C-dependent signaling pathway inhibitors was also examined and indicated that this pathway may mediate dendrimer-induced changes in permeability. Differences between G3.5 and G4 in tight junction protein staining and permeability with inhibitors were evident, suggesting divergent mechanisms were responsible for tight junction modulation. These dissimilarities are further intimated by the intracellular calcium release caused by G4 but not G3.5. Based on our results, it is apparent that the underlying mechanisms of dendrimer permeability are complex, and the complexities are likely a result of the density and sign of the surface charges of PAMAM dendrimers. The results of this study will have implications on the future use of PAMAM dendrimers for oral drug delivery.

  9. Nanomedicine for prion disease treatment: new insights into the role of dendrimers.

    Science.gov (United States)

    McCarthy, James M; Appelhans, Dietmar; Tatzelt, Jörg; Rogers, Mark S

    2013-01-01

    Despite their devastating impact, no effective therapeutic yet exists for prion diseases at the symptomatic stage in humans or animals. Progress is hampered by the difficulty in identifying compounds that affect PrP (Sc) and the necessity of any potential therapeutic to gain access to the CNS. Synthetic polymers known as dendrimers are a particularly promising candidate in this area. Studies with cell culture models of prion disease and prion infected brain homogenate have demonstrated that numerous species of dendrimers eliminate PrP (Sc) in a dose and time dependent fashion and specific glycodendrimers are capable of crossing the CNS. However, despite their potential a number of important questions remained unanswered such as what makes an effective dendrimer and how dendrimers eliminate prions intracellularly. In a number of recent studies we have tackled these questions and revealed for the first time that a specific dendrimer can inhibit the intracellular conversion of PrP (C) to PrP (Sc) and that a high density of surface reactive groups is a necessity for dendrimers in vitro anti-prion activity. Understanding how a therapeutic works is a vital component in maximising its activity and these studies therefore represent a significant development in the race to find effective treatments for prion diseases.

  10. Engineering CNDP's of dendrimers containing phosphorous interior compositions to produce new emerging properties

    Science.gov (United States)

    Caminade, Anne-Marie; Majoral, Jean-Pierre

    2018-03-01

    Phosphorus-containing dendrimers are defined as dendrimers having at least one phosphorus atom at each branching point. In this review, we will show how phosphorhydrazone dendrimers can be modified at will at the level of the core and of the branches, to afford specific properties, such as fluorescence to image biological events. Accelerated methods of synthesis of phosphorus (one step for one generation) will be also displayed, as well as the specific reactivity of P=N-P=S linkages obtained in most of these accelerated method of synthesis, which has led to particularly original dendritic architectures, such as dendrons included in dendrimers. Finally, we will display how modifications of the internal structure of a series of dendrimers having the same type and number of terminal functions can deeply modify their biological anti-inflammatory properties. Among the six critical nanoscale design parameters (CNDP), we will show how two of them, i.e., architecture and elemental composition, have been particularly engineered to modify phosphorus-containing dendrimers, in order to fulfill the desired properties.

  11. Cationic Phosphorus Dendrimer Enhances Photodynamic Activity of Rose Bengal against Basal Cell Carcinoma Cell Lines.

    Science.gov (United States)

    Dabrzalska, Monika; Janaszewska, Anna; Zablocka, Maria; Mignani, Serge; Majoral, Jean Pierre; Klajnert-Maculewicz, Barbara

    2017-05-01

    In the last couple of decades, photodynamic therapy emerged as a useful tool in the treatment of basal cell carcinoma. However, it still meets limitations due to unfavorable properties of photosensitizers such as poor solubility or lack of selectivity. Dendrimers, polymers widely studied in biomedical field, may play a role as photosensitizer carriers and improve the efficacy of photodynamic treatment. Here, we describe the evaluation of an electrostatic complex of cationic phosphorus dendrimer and rose bengal in such aspects as singlet oxygen production, cellular uptake, and phototoxicity against three basal cell carcinoma cell lines. Rose bengal-cationic dendrimer complex in molar ratio 5:1 was compared to free rose bengal. Obtained results showed that the singlet oxygen production in aqueous medium was significantly higher for the complex than for free rose bengal. The cellular uptake of the complex was 2-7-fold higher compared to a free photosensitizer. Importantly, rose bengal, rose bengal-dendrimer complex, and dendrimer itself showed no dark toxicity against all three cell lines. Moreover, we observed that phototoxicity of the complex was remarkably enhanced presumably due to high cellular uptake. On the basis of the obtained results, we conclude that rose bengal-cationic dendrimer complex has a potential in photodynamic treatment of basal cell carcinoma.

  12. Molecular dynamics simulations of single siloxane dendrimers: Molecular structure and intramolecular mobility of terminal groups

    Science.gov (United States)

    Kurbatov, A. O.; Balabaev, N. K.; Mazo, M. A.; Kramarenko, E. Yu.

    2018-01-01

    Molecular dynamics simulations of two types of isolated siloxane dendrimers of various generations (from the 2nd to the 8th) have been performed for temperatures ranging from 150 K to 600 K. The first type of dendrimer molecules has short spacers consisting of a single oxygen atom. In the dendrimers of the second type, spacers are longer and comprised of two oxygen atoms separated by a single silicon atom. A comparative analysis of molecular macroscopic parameters such as the gyration radius and the shape factor as well as atom distributions within dendrimer interior has been performed for varying generation number, temperature, and spacer length. It has been found that the short-spacer dendrimers of the 7th and 8th generations have a stressed central part with elongated bonds and deformed valence angles. Investigation of the time evolution of radial displacements of the terminal Si atoms has shown that a fraction of the Si groups have a reduced mobility. Therefore, rather long time trajectories (of the order of tens of nanoseconds) are required to study dendrimer intramolecular dynamics.

  13. Molecular Determinants of the Cellular Entry of Asymmetric Peptide Dendrimers and Role of Caveolae.

    Directory of Open Access Journals (Sweden)

    Prarthana V Rewatkar

    Full Text Available Caveolae are flask-shaped plasma membrane subdomains abundant in most cell types that participate in endocytosis. Caveola formation and functions require membrane proteins of the caveolin family, and cytoplasmic proteins of the cavin family. Cationic peptide dendrimers are non-vesicular chemical carriers that can transport pharmacological agents or genetic material across the plasma membrane. We prepared a panel of cationic dendrimers and investigated whether they require caveolae to enter into cells. Cell-based studies were performed using wild type or caveola-deficient i.e. caveolin-1 or PTRF gene-disrupted cells. There was a statistically significant difference in entry of cationic dendrimers between wild type and caveola-deficient cells. We further unveiled differences between dendrimers with varying charge density and head groups. Our results show, using a molecular approach, that (i expression of caveola-forming proteins promotes cellular entry of cationic dendrimers and (ii dendrimer structure can be modified to promote endocytosis in caveola-forming cells.

  14. COMPUTER SIMULATION OF LOCAL MOBILITY IN DENDRIMERS WITH ASYMMETRIC BRANCHING BY BROWNIAN DYNAMICS METHOD

    Directory of Open Access Journals (Sweden)

    O. V. Shavykin

    2016-09-01

    Full Text Available The Brownian dynamics method has been used to study the effect of the branching asymmetry on the local orientational mobility of segments and bonds in dendrimers in good solvent. “Coarse-grained” models of flexible dendrimers with different branching symmetry but with the same average segment length were considered. The frequency dependences of the rate of the spin-lattice relaxation nuclear magnetic resonance (NMR [1/T1H(H] for segments or bonds located at different distances from terminal monomers were calculated. After the exclusion of the contribution of the overall dendrimer rotation the position of the maxima of the frequency dependences [1/T1H(ωH] for different segments with the same length doesn’t depend on their location inside a dendrimer both for phantom models and for models with excluded volume interactions. This effect doesn’t depend also on the branching symmetry, but the position of the maximum [1/T1H(ωH] is determined by the segment length. For bonds inside segments the positions of the maximum [1/T1H(ωH] coincide for all models considered. Therefore, the obtained earlier conclusion about the weak influence of the excluded volume interactions on the local dynamics in the flexible symmetric dendrimers can be generalized for dendrimers with an asymmetric branching.

  15. Effect of increased surface hydrophobicity via drug conjugation on the clearance of inhaled PEGylated polylysine dendrimers.

    Science.gov (United States)

    Haque, Shadabul; McLeod, Victoria M; Jones, Seth; Fung, Sandy; Whittaker, Michael; McIntosh, Michelle; Pouton, Colin; Owen, David J; Porter, Christopher J H; Kaminskas, Lisa M

    2017-10-01

    PEGylated polylysine dendrimers are attractive and well tolerated inhalable drug delivery platforms that have the potential to control the release, absorption kinetics and lung retention time of conjugated drugs. The clinical application of these systems though, would likely require partial substitution of surface PEG groups with drug molecules that are anticipated to alter their lung clearance kinetics and clearance pathways. In the current study, we therefore evaluated the impact of increased surface hydrophobicity via substitution of 50% surface PEG groups with a model hydrophobic drug (α-carboxyl OtButylated methotrexate) on the lung clearance of a Generation 5 PEGylated polylysine dendrimer in rats. PEG substitution with OtBu-methotrexate accelerated lung clearance of the dendrimer by increasing polylysine scaffold catabolism, improving systemic absorption of the intact dendrimer and low molecular weight products of scaffold catabolism, and enhancing mucociliary clearance. These results suggest that the conjugation of hydrophobic drug on the surface of a PEGylated dendrimer is likely to accelerate lung clearance when compared to a fully PEGylated dendrimer. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  16. Supramolecular assembly of a series of chiral dendrimers in interfacial films

    International Nuclear Information System (INIS)

    Yuan Jing; Deng Guojun; Fan Qinghua; Liu Minghua

    2004-01-01

    Supramolecular assembly and interfacial properties of a series of novel binaphthyl containing dendrimers from generation 1 through generation 4 have been investigated at the air/water interface and in solid substrates. Due to the lack of either long alkyl chains or strong hydrophilic groups, the dendrimer molecules tend to aggregate together to form stable two-dimensional ultrathin films, as verified by π-A and A-t measurements. Atomic force microscope (AFM) measurements of the transferred one-layer ultrathin films indicate that all the dendrimers show disk-like morphologies, which could be varied in particle size upon changing the surface pressure. The height profiles reveal that the height of the disks is between that of a monolayer and a bilayer, indicating that they are formed due to the aggregation of dendrimers with a distortion and/or partial overlapping. Circular dichroism (CD) spectra of the transferred multilayer films show Cotton effects due to the exciton couplet of the aromatic moieties adjacent to the bis(diphenylphosphino)-binaphthyl moiety, which is an active catalytic site for the dendrimer. With the increment of the generation, the intensity of the Cotton effects increased, suggesting that the optical active site of the dendrimer can be controlled by the outside wedge

  17. Dendrimer Nanoscaffolds for Potential Theranostics of Prostate Cancer with a Focus on Radiochemistry

    Science.gov (United States)

    Lo, Su-Tang; Kumar, Amit; Hsieh, Jer-Tsong; Sun, Xiankai

    2013-01-01

    Dendrimers are a class of structurally defined macromolecules featured with a central core, a low-density interior formed by repetitive branching units, and a high-density exterior terminated with surface functional groups. In contrast to their polymeric counterparts, dendrimers are nano-sized and symmetrically shaped, which can be reproducibly synthesized in a large scale with monodispersity. These unique features have made dendrimers of increasing interest for drug delivery and other biomedical applications as a nanoscaffold system. Intended to address the potential use of dendrimers for the development of theranostic agents, which combines therapeutics and diagnostics in a single entity for personalized medicine, this review focuses on the reported methodologies of using dendrimer nanoscaffolds for targeted imaging and therapy of prostate cancer. Of particular interest, relevant chemistry strategies are discussed due to their important roles in the design and synthesis of diagnostic and therapeutic dendrimer-based nanoconjugates and potential theranostic agents, targeted or non-targeted. Given the developing status of nanoscaffolded theranostics, major challenges and potential hurdles are discussed along with the examples representing current advances. PMID:23294202

  18. Precise localization of metal nanoparticles in dendrimer nanosnakes or inner periphery and consequences in catalysis

    Science.gov (United States)

    Liu, Xiang; Gregurec, Danijela; Irigoyen, Joseba; Martinez, Angel; Moya, Sergio; Ciganda, Roberto; Hermange, Philippe; Ruiz, Jaime; Astruc, Didier

    2016-10-01

    Understanding the relationship between the location of nanoparticles (NPs) in an organic matrix and their catalytic performances is essential for catalyst design. Here we show that catalytic activities of Au, Ag and CuNPs stabilized by dendrimers using coordination to intradendritic triazoles, galvanic replacement or stabilization outside dendrimers strongly depends on their location. AgNPs are found at the inner click dendrimer periphery, whereas CuNPs and AuNPs are encapsulated in click dendrimer nanosnakes. AuNPs and AgNPs formed by galvanic replacement are larger than precursors and only partly encapsulated. AuNPs are all the better 4-nitrophenol reduction catalysts as they are less sterically inhibited by the dendrimer interior, whereas on the contrary CuNPs are all the better alkyne azide cycloaddition catalysts as they are better protected from aerobic oxidation inside dendrimers. This work highlights the role of the location in macromolecules on the catalytic efficiency of metal nanoparticles and rationalizes optimization in catalyst engineering.

  19. Molecular Determinants of the Cellular Entry of Asymmetric Peptide Dendrimers and Role of Caveolae.

    Science.gov (United States)

    Rewatkar, Prarthana V; Parekh, Harendra S; Parat, Marie-Odile

    2016-01-01

    Caveolae are flask-shaped plasma membrane subdomains abundant in most cell types that participate in endocytosis. Caveola formation and functions require membrane proteins of the caveolin family, and cytoplasmic proteins of the cavin family. Cationic peptide dendrimers are non-vesicular chemical carriers that can transport pharmacological agents or genetic material across the plasma membrane. We prepared a panel of cationic dendrimers and investigated whether they require caveolae to enter into cells. Cell-based studies were performed using wild type or caveola-deficient i.e. caveolin-1 or PTRF gene-disrupted cells. There was a statistically significant difference in entry of cationic dendrimers between wild type and caveola-deficient cells. We further unveiled differences between dendrimers with varying charge density and head groups. Our results show, using a molecular approach, that (i) expression of caveola-forming proteins promotes cellular entry of cationic dendrimers and (ii) dendrimer structure can be modified to promote endocytosis in caveola-forming cells.

  20. Synthesis of New Functionalized Citric Acid-based Dendrimers as Nanocarrier Agents for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Sanaz Motamedi

    2011-06-01

    Full Text Available Introduction: Citric acid-polyethylene glycol-citric acid (CPEGC triblock dendrimers can serve as potential delivery systems. Methods: In this investigation, CPEGC triblock dendrimers were synthesized and then imidazole groups were conjugated onto the surface of the G1, G2 and G3 of the obtained dendrimers. In order to study the type of the interactions between the functionalized dendrimers and a drug molecule, Naproxen which contains acidic groups, was examined as a hydrophobic drug in which the interactions would be of the electrostatic kind between its acidic groups and the lone pair electrons of nitrogen atom in imidazole groups. The quantity of the trapped drug and also the amount of its release were measured with UV spectrometric method in pH 1, 7.4 and 10. The average diameter of the nanocarriers was measured by Dynamic Light Scattering (DLS technique Results: The size range of particles was determined to be 16-50 nm for different generations. The rate of the release increased in pH=10 in all generations due to the increase in Naproxen solubility and the hydrolysis of the esteric bonds in the mentioned pH. The results showed that the amount of the trapped drug increased with the increase in the generation of the dendrimer and pH. Conclusion: Based on our findings, we suggest CPEGC triblock dendrimers possess great potential to be used as drug/gene delivery system.

  1. Interactions of PAMAM dendrimers with SDS at the solid-liquid interface.

    Science.gov (United States)

    Arteta, Marianna Yanez; Eltes, Felix; Campbell, Richard A; Nylander, Tommy

    2013-05-14

    This work addresses structural and nonequilibrium effects of the interactions between well-defined cationic poly(amidoamine) PAMAM dendrimers of generations 4 and 8 and the anionic surfactant sodium dodecyl sulfate (SDS) at the hydrophilic silica-water interface. Neutron reflectometry and quartz crystal microbalance with dissipation monitoring were used to reveal the adsorption from premixed dendrimer/surfactant solutions as well as sequential addition of the surfactant to preadsorbed layers of dendrimers. PAMAM dendrimers of both generations adsorb to hydrophilic silica as a compact monolayer, and the adsorption is irreversible upon rinsing with salt solution. SDS adsorbs on the dendrimer layer and at low bulk concentrations causes the expansion of the dendrimer layers on the surface. When the bulk concentration of SDS is increased, the surfactant layer consists of aggregates or bilayer-like structures. The adsorption of surfactant is reversible upon rinsing, but slight changes of the structure of the preadsorbed PAMAM monolayer were observed. The adsorption from premixed solutions close to charge neutrality results in thick multilayers, but the surface excess is lower when the bulk complexes have a net negative charge. A critical examination of the pathway of adsorption for the interactions of SDS with preadsorbed PAMAM monolayers and premixed PAMAM/SDS solutions with hydrophilic silica revealed that nonequilibrium effects are important only in the latter case, and the application of a thermodynamic model to such experimental data would be inappropriate.

  2. Different patterns of nuclear and mitochondrial penetration by the G3 PAMAM dendrimer and its biotin–pyridoxal bioconjugate BC-PAMAM in normal and cancer cells in vitro

    Directory of Open Access Journals (Sweden)

    Uram Ł

    2015-09-01

    investigated concentrations, with lower level (15%–25% observed for BC-PAMAM. In fibroblasts, the dendrimer nuclear signal amounted to 15% at nontoxic and up to 70% at toxic concentrations, whereas BC-PAMAM remained at a lower concentration-dependent level (0.3%–20%. Mitochondrial localization of PAMAM and BC-PAMAM revealed similar patterns in both cell lines, depending on the extracellular dendrimer concentration, and presented significantly lower signals from BC-PAMAM, which correlated well with the cytotoxicity. Keywords: PAMAM G3 dendrimer, bioconjugate, normal and cancer cells, nuclei, mitochondria, confocal microscopy, colocalization

  3. Enhanced Intestinal Permeability of Bufalin by a Novel Bufalin-Peptide-Dendrimer Inclusion through Caco-2 Cell Monolayer

    Directory of Open Access Journals (Sweden)

    Chi-on Chan

    2017-11-01

    Full Text Available Bufalin (BFL has excellent physiological activities such as defending tumors, improving cardiac function, and so on. However, due to its poor water-solubility and bioavailability, the clinical application of BFL remains limited. In order to improve bioavailability of BFL, in our previous research, a novel peptide-dendrimer (PD was synthesized and applied to encapsulate BFL. In the present study, we investigate the absorption property and mechanism of BFL in free form and BFL-peptide-dendrimer inclusion (BPDI delivery system by using the Caco-2 cell monolayer model in vitro. The apparent permeability coefficient (Papp values of BFL in free or BPDI form were over 1.0 × 10−6 cm/s. Meanwhile, their almost equal bi-directional transport and linear transport percentage with time and concentration course indicated that BFL in both forms was absorbed mainly through passive diffusion. The most important result is that the Papp values of BFL increased about three-fold more BPDI than those of its free form, which indicated the intestinal permeability of BFL could be improved while BFL was encapsulated in BPDI form. Therefore, PD encapsulation may be a potential delivery system to increase the bioavailability of BFL.

  4. Radiolabeling optimization and characterization of (68)Ga labeled DOTA-polyamido-amine dendrimer conjugate - Animal biodistribution and PET imaging results.

    Science.gov (United States)

    Ghai, Aanchal; Singh, Baljinder; Panwar Hazari, Puja; Schultz, Michael K; Parmar, Ambika; Kumar, Pardeep; Sharma, Sarika; Dhawan, Devinder; Kumar Mishra, Anil

    2015-11-01

    The present study describes the optimization of (68)Ga radiolabeling with PAMAM dendrimer-DOTA conjugate. A conjugate (PAMAM-DOTA) concentration of 11.69µM, provided best radiolabeling efficiency of more than 93.0% at pH 4.0, incubation time of 30.0min and reaction temperature ranging between 90 and 100°C. The decay corrected radiochemical yield was found to be 79.4±0.01%. The radiolabeled preparation ([(68)Ga]-DOTA-PAMAM-D) remained stable (radiolabeling efficiency of 96.0%) at room temperature and in serum for up to 4-h. The plasma protein binding was observed to be 21.0%. After intravenous administration, 50.0% of the tracer cleared from the blood circulation by 30-min and less than 1.0% of the injected activity remained in blood by 1.0h. The animal biodistribution studies demonstrated that the tracer excretes through the kidneys and about 0.33% of the %ID/g accumulated in the tumor at 1h post injection. The animal organ's biodistribution data was supported by animal PET imaging showing good 'non-specific' tracer uptake in tumor and excretion is primarily through kidneys. Additionally, DOTA-PAMAM-D conjugation with αVβ3 receptors targeting peptides and drug loading on the dendrimers may improve the specificity of the (68)Ga labeled product for imaging and treating angiogenesis respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. ANTI-INFLAMMATORY EFFECT OF ANTI-TNF-ALPHA siRNA CATIONIC PHOSPHOROUS DENDRIMERS NANOCOMPLEXES ADMINISTERED INTRANASALLY IN A MURINE ACUTE LUNG INJURY MODEL

    DEFF Research Database (Denmark)

    Bohr, Adam; Tsapis, Nicolas; Andreana, Ilaria

    2017-01-01

    lung injury model. To achieve this goal, two different types of phosphorus-based dendrimers with either pyrrolidinium or morpholinium as terminal protonated amino groups were selected for their better biocompatibility compared to other dendrimers. Dendriplexes containing pyrrolidinium surface groups...

  6. Small Angle Neutron Scattering Studies of the Counterion Effects on the Molecular Conformation and Structure of Charged G4 PAMAM Dendrimers in Aqueous Solutions

    International Nuclear Information System (INIS)

    Chen, Wei-Ren

    2007-01-01

    The structural properties of generation 4 (G4) poly(amidoamine) starburst dendrimers (PAMAM) with an ethylenediamine ne (EDA) central core in D O 2 solutions have been studied by small angle neutron scattering. Upon the addition of DCl , SANS patterns show a pronounced inter-particle 2 correlation peaks due to the strong repulsion introduced by the protonation of the amino groups of the dendrimers. By solving the Ornstein-Zernike integral equation (OZ) with hypernetted chain closure (HNC), the dendrimer-dendrimer er structure factor S(Q) is determined and used to fit the experimental data. Quantitative information such as the effective charge per dendrimer and its conformational change at different conditions can be obtained. The results obtained show clear evidence that significant counterion association occurs, strongly mediating the inter-dendrimer interaction. The influence of interplay between counterions and molecular protonation of dendrimers has strong effect on the dendrimer conformation and effective interaction.

  7. Design of different strategies of multivalent DNA-based vaccination against rabies and canine distemper in mice and dogs

    Directory of Open Access Journals (Sweden)

    Touihri Leila

    2012-12-01

    Full Text Available Abstract Background During the vaccination campaigns, puppies younger than 3 months old are not targeted and remain unvaccinated for at least the first year of their lives. Almost half of the reported rabid dogs are 6 months or younger. Hence, we should recommend the vaccination against rabies of young puppies. Unfortunately, owing to the exposure of puppies to infections with either canine parvovirus (CPV or distemper virus (CDV after the intervention of the vaccinators, owners are reluctant to vaccinate puppies against rabies. Therefore, it is necessary to include the CPV and CDV valences in the vaccine against rabies. Multivalent DNA-based vaccination in dogs, including rabies and distemper valences, could help in raising vaccine coverage. Methods We have designed monovalent and multivalent DNA-based vaccine candidates for in vitro and in vivo assays. These plasmids encode to the rabies virus glycoprotein and/or the canine distemper virus hemagglutinin. The first strategy of multivalent DNA-based vaccination is by mixing plasmids encoding to a single antigen each. The second is by simply fusing the genes of the antigens together. The third is by adding the foot and mouth disease virus (FMDV 2A oligopeptide gene into the antigen genes. The last strategy is by the design and use of a bicistronic plasmid with an “Internal Ribosome Entry Site” (IRES domain. Results The monovalent construct against canine distemper was efficiently validated by inducing higher humoral immune responses compared to cell-culture-derived vaccine both in mice and dogs. All multivalent plasmids efficiently expressed both valences after in vitro transfection of BHK-21 cells. In BALB/c mice, the bicistronic IRES-dependant construct was the most efficient inducer of virus-neutralizing antibodies against both valences. It was able to induce better humoral immune responses compared to the administration of either cell-culture-derived vaccines or monovalent plasmids. The

  8. Design of different strategies of multivalent DNA-based vaccination against rabies and canine distemper in mice and dogs.

    Science.gov (United States)

    Touihri, Leila; Ahmed, Sami Belhaj; Chtourou, Yacine; Daoud, Rahma; Bahloul, Chokri

    2012-12-27

    During the vaccination campaigns, puppies younger than 3 months old are not targeted and remain unvaccinated for at least the first year of their lives. Almost half of the reported rabid dogs are 6 months or younger. Hence, we should recommend the vaccination against rabies of young puppies. Unfortunately, owing to the exposure of puppies to infections with either canine parvovirus (CPV) or distemper virus (CDV) after the intervention of the vaccinators, owners are reluctant to vaccinate puppies against rabies. Therefore, it is necessary to include the CPV and CDV valences in the vaccine against rabies. Multivalent DNA-based vaccination in dogs, including rabies and distemper valences, could help in raising vaccine coverage. We have designed monovalent and multivalent DNA-based vaccine candidates for in vitro and in vivo assays. These plasmids encode to the rabies virus glycoprotein and/or the canine distemper virus hemagglutinin. The first strategy of multivalent DNA-based vaccination is by mixing plasmids encoding to a single antigen each. The second is by simply fusing the genes of the antigens together. The third is by adding the foot and mouth disease virus (FMDV) 2A oligopeptide gene into the antigen genes. The last strategy is by the design and use of a bicistronic plasmid with an "Internal Ribosome Entry Site" (IRES) domain. The monovalent construct against canine distemper was efficiently validated by inducing higher humoral immune responses compared to cell-culture-derived vaccine both in mice and dogs. All multivalent plasmids efficiently expressed both valences after in vitro transfection of BHK-21 cells. In BALB/c mice, the bicistronic IRES-dependant construct was the most efficient inducer of virus-neutralizing antibodies against both valences. It was able to induce better humoral immune responses compared to the administration of either cell-culture-derived vaccines or monovalent plasmids. The FMDV 2A was also efficient in the design of multivalent

  9. Peptide Dendrimer/Lipid Hybrid Systems Are Efficient DNA Transfection Reagents: Structure–Activity Relationships Highlight the Role of Charge Distribution Across Dendrimer Generations

    Science.gov (United States)

    2013-01-01

    Efficient DNA delivery into cells is the prerequisite of the genetic manipulation of organisms in molecular and cellular biology as well as, ultimately, in nonviral gene therapy. Current reagents, however, are relatively inefficient, and structure–activity relationships to guide their improvement are hard to come by. We now explore peptide dendrimers as a new type of transfection reagent and provide a quantitative framework for their evaluation. A collection of dendrimers with cationic and hydrophobic amino acid motifs (such as KK, KA, KH, KL, and LL) distributed across three dendrimer generations was synthesized by a solid-phase protocol that provides ready access to dendrimers in milligram quantities. In conjunction with a lipid component (DOTMA/DOPE), the best reagent, G1,2,3-KL ((LysLeu)8(LysLysLeu)4(LysLysLeu)2LysGlySerCys-NH2), improves transfection by 6–10-fold over commercial reagents under their respective optimal conditions. Emerging structure–activity relationships show that dendrimers with cationic and hydrophobic residues distributed in each generation are transfecting most efficiently. The trigenerational dendritic structure has an advantage over a linear analogue worth up to an order of magnitude. The success of placing the decisive cationic charge patterns in inner shells rather than previously on the surface of macromolecules suggests that this class of dendrimers significantly differs from existing transfection reagents. In the future, this platform may be tuned further and coupled to cell-targeting moieties to enhance transfection and cell specificity. PMID:23682947

  10. Analysis of Biotinylated Generation 4 Poly(amidoamine (PAMAM Dendrimer Distribution in the Rat Brain and Toxicity in a Cellular Model of the Blood-Brain Barrier

    Directory of Open Access Journals (Sweden)

    Heather A. Bullen

    2013-09-01

    Full Text Available Dendrimers are highly customizable nanopolymers with qualities that make them ideal for drug delivery. The high binding affinity of biotin/avidin provides a useful approach to fluorescently label synthesized dendrimer-conjugates in cells and tissues. In addition, biotin may facilitate delivery of dendrimers through the blood-brain barrier (BBB via carrier-mediated endocytosis. The purpose of this research was to: (1 measure toxicity using lactate dehydrogenase (LDH assays of generation (G4 biotinylated and non-biotinylated poly(amidoamine (PAMAM dendrimers in a co-culture model of the BBB, (2 determine distribution of dendrimers in the rat brain, kidney, and liver following systemic administration of dendrimers, and (3 conduct atomic force microscopy (AFM on rat brain sections following systemic administration of dendrimers. LDH measurements showed that biotinylated dendrimers were toxic to cell co-culture after 48 h of treatment. Distribution studies showed evidence of biotinylated and non-biotinylated PAMAM dendrimers in brain. AFM studies showed evidence of dendrimers only in brain tissue of treated rats. These results indicate that biotinylation does not decrease toxicity associated with PAMAM dendrimers and that biotinylated PAMAM dendrimers distribute in the brain. Furthermore, this article provides evidence of nanoparticles in brain tissue following systemic administration of nanoparticles supported by both fluorescence microscopy and AFM.

  11. Interaction of poly(amidoamine) dendrimers with supported lipid bilayers and cells: hole formation and the relation to transport.

    Science.gov (United States)

    Hong, Seungpyo; Bielinska, Anna U; Mecke, Almut; Keszler, Balazs; Beals, James L; Shi, Xiangyang; Balogh, Lajos; Orr, Bradford G; Baker, James R; Banaszak Holl, Mark M

    2004-01-01

    We have investigated poly(amidoamine) (PAMAM) dendrimer interactions with supported 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid bilayers and KB and Rat2 cell membranes using atomic force microscopy (AFM), enzyme assays, flow cell cytometry, and fluorescence microscopy. Amine-terminated generation 7 (G7) PAMAM dendrimers (10-100 nM) were observed to form holes of 15-40 nm in diameter in aqueous, supported lipid bilayers. G5 amine-terminated dendrimers did not initiate hole formation but expanded holes at existing defects. Acetamide-terminated G5 PAMAM dendrimers did not cause hole formation in this concentration range. The interactions between PAMAM dendrimers and cell membranes were studied in vitro using KB and Rat 2 cell lines. Neither G5 amine- nor acetamide-terminated PAMAM dendrimers were cytotoxic up to a 500 nM concentration. However, the dose dependent release of the cytoplasmic proteins lactate dehydrogenase (LDH) and luciferase (Luc) indicated that the presence of the amine-terminated G5 PAMAM dendrimer decreased the integrity of the cell membrane. In contrast, the presence of acetamide-terminated G5 PAMAM dendrimer had little effect on membrane integrity up to a 500 nM concentration. The induction of permeability caused by the amine-terminated dendrimers was not permanent, and leaking of cytosolic enzymes returned to normal levels upon removal of the dendrimers. The mechanism of how PAMAM dendrimers altered cells was investigated using fluorescence microscopy, LDH and Luc assays, and flow cytometry. This study revealed that (1) a hole formation mechanism is consistent with the observations of dendrimer internalization, (2) cytosolic proteins can diffuse out of the cell via these holes, and (3) dye molecules can be detected diffusing into the cell or out of the cell through the same membrane holes. Diffusion of dendrimers through holes is sufficient to explain the uptake of G5 amine-terminated PAMAM dendrimers into cells and is consistent

  12. Macromolecular and dendrimer-based magnetic resonance contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Bumb, Ambika; Brechbiel, Martin W. (Radiation Oncology Branch, National Cancer Inst., National Inst. of Health, Bethesda, MD (United States)), e-mail: pchoyke@mail.nih.gov; Choyke, Peter (Molecular Imaging Program, National Cancer Inst., National Inst. of Health, Bethesda, MD (United States))

    2010-09-15

    Magnetic resonance imaging (MRI) is a powerful imaging modality that can provide an assessment of function or molecular expression in tandem with anatomic detail. Over the last 20-25 years, a number of gadolinium-based MR contrast agents have been developed to enhance signal by altering proton relaxation properties. This review explores a range of these agents from small molecule chelates, such as Gd-DTPA and Gd-DOTA, to macromolecular structures composed of albumin, polylysine, polysaccharides (dextran, inulin, starch), poly(ethylene glycol), copolymers of cystamine and cystine with GD-DTPA, and various dendritic structures based on polyamidoamine and polylysine (Gadomers). The synthesis, structure, biodistribution, and targeting of dendrimer-based MR contrast agents are also discussed

  13. Controlled doping by self-assembled dendrimer-like macromolecules

    Science.gov (United States)

    Wu, Haigang; Guan, Bin; Sun, Yingri; Zhu, Yiping; Dan, Yaping

    2017-02-01

    Doping via self-assembled macromolecules might offer a solution for developing single atom electronics by precisely placing individual dopants at arbitrary location to meet the requirement for circuit design. Here we synthesize dendrimer-like polyglycerol macromolecules with each carrying one phosphorus atom in the core. The macromolecules are immobilized by the coupling reagent onto silicon surfaces that are pre-modified with a monolayer of undecylenic acid. Nuclear magnetic resonance (NMR) and X-ray photoelectron spectroscopy (XPS) are employed to characterize the synthesized macromolecules and the modified silicon surfaces, respectively. After rapid thermal annealing, the phosphorus atoms carried by the macromolecules diffuse into the silicon substrate, forming dopants at a concentration of 1017 cm-3. Low-temperature Hall effect measurements reveal that the ionization process is rather complicated. Unlike the widely reported simple ionization of phosphorus dopants, nitrogen and carbon are also involved in the electronic activities in the monolayer doped silicon.

  14. Thiophene dendrimer-based low donor content solar cells

    Science.gov (United States)

    Stoltzfus, Dani M.; Ma, Chang-Qi; Nagiri, Ravi C. R.; Clulow, Andrew J.; Bäuerle, Peter; Burn, Paul L.; Gentle, Ian R.; Meredith, Paul

    2016-09-01

    Low donor content solar cells containing polymeric and non-polymeric donors blended with fullerenes have been reported to give rise to efficient devices. In this letter, we report that a dendrimeric donor can also be used in solution-processed low donor content devices when blended with a fullerene. A third generation dendrimer containing 42 thiophene units (42T) was found to give power conversion efficiencies of up to 3.5% when blended with PC70BM in optimized devices. The best efficiency was measured with 10 mole percent (mol. %) of 42T in PC70BM and X-ray reflectometry showed that the blends were uniform. Importantly, while 42T comprised 10 mol. % of the film, it made up 31% of the film by volume. Finally, it was found that solvent annealing was required to achieve the largest open circuit voltage and highest device efficiencies.

  15. Transport of optical excitations on dendrimers in the continuum approximation

    International Nuclear Information System (INIS)

    Vlaming, S.M.; Heijs, D.J.; Knoester, J.

    2005-01-01

    We study the incoherent transport of optical excitations created at the rim of a dendritic molecule to a trap occurring at the core. The corresponding discrete random walk is treated in a continuum approximation, resulting in a diffusion-like process which admits semi-analytical solutions. The thus obtained arrival time distribution for the excitation at the trap is compared with the one for the original, discrete problem. In the case of an inward bias or even a weak outward one, the agreement is very good and the continuum approximation provides a good alternative description of the energy transfer process, even for small dendrimers. In the case of a strong outward bias, the mean trapping time, which sets the time scale for the entire distribution, depends exponentially on the number of generations in both approaches, but with a different base. The failure of the continuum approximation for this case is explained from the peaked behavior of the excitation density near the rim

  16. Donor doping process and white light generation in CaMoO4 powders with multivalence Pr codoping

    International Nuclear Information System (INIS)

    Zhu Fang; Xiao Zhisong; Zhang Feng; Yan Lu; Huang Anping

    2011-01-01

    Both trivalent praseodymium (Pr 3+ ) and quadrivalent praseodymium (Pr 4+ ) were doped in molybdate powders. Visible emission from matrix was enhanced by multivalent Pr codoping. It was proposed that Pr 3+ ions was donor and supplied quasi-free electron when Pr 3+ took place the Pr 4+ sites. The result showed that multivalence codoping would be an effective way to enhance emission of CaMoO 4 . White light can be generated from Ca 0.98 Pr 0.02 MoO 4 powder via combination of broadband emissions originated from CaMoO 4 matrix and radiative transition of Pr 3+ . It showed warm white light with T c of 3450 K that implies promising application in white light emitting diodes (LEDs).

  17. Multivalent system for therapy of non-Hod king lymphomas based on Anti-CD20 conjugated to gold nanoparticles

    International Nuclear Information System (INIS)

    Miranda O, R. M.

    2014-01-01

    In recent publications has been reported that gold nanoparticles have an effect in reducing the expression of the oncogene Bcl -2 and have a high biocompatibility , this is the importance for using gold nanoparticles for this work. The antibody CD20 is an antibody that specifically binds to that over expressed CD20 antigen on the cell membrane of B lymphoma cell non- Hodgkin (cell line Raji) behold the importance of combining this bio molecule to gold nanoparticles since they have a high specificity with CD20 positive cells , also to carry out the antigen- antibody immunological reactions triggered mediating cell lysis, possibly by cytotoxicity and apoptosis. Therefore, this system must have characteristics of both components to eliminate B cell non- Hodgkin lymphoma.In this work it was studied a multivalent system composed of gold nanoparticles and anti-CD20 antibody, the term multi valency refers to the number of biomolecules attached to the surface of the gold nanoparticle. The synthesis and characterization of the gold nanoparticles and the multivalent system was performed and the effect of the multivalent system on the expression of oncogene Bcl-2 (group of proteins associated with the apoptotic pathway) was evaluated. Characterization of raw materials and the multivalent system was performed using spectroscopic and microscopic techniques, this to verify structural changes in raw materials and thus confirm the formation of CD20 binding to the surface of the nanoparticle gold by the bond between gold and sulfur in the cysteines of CD20. Taking advantage that the metal nanoparticles have the optical property of surface plasmon resonance, the absorption of gold nanoparticles was measured on the UV-Vis as it is affected by the surface molecules bind to it, showing a bathochromic displacement effected. The hydrodynamic diameter of the gold nanoparticles was measured to verify that the antibody is bound to the surface; this evidence was complemented by micrographs

  18. Microglial migration and interactions with dendrimer nanoparticles are altered in the presence of neuroinflammation.

    Science.gov (United States)

    Zhang, Fan; Nance, Elizabeth; Alnasser, Yossef; Kannan, Rangaramanujam; Kannan, Sujatha

    2016-03-22

    Microglial cells have been implicated in neuroinflammation-mediated injury in the brain, including neurodevelopmental disorders such as cerebral palsy (CP) and autism. Pro-inflammatory activation of microglial cells results in the impairment of their neuroprotective functions, leading to an exaggerated, ongoing immune dysregulation that can persist long after the initial insult. We have previously shown that dendrimer-mediated delivery of an anti-inflammatory agent can attenuate inflammation in a rabbit model of maternal inflammation-induced CP and significantly improve the motor phenotype, due to the ability of the dendrimer to selectively localize in activated microglia. To elucidate the interactions between dendrimers and microglia, we created an organotypic whole-hemisphere brain slice culture model from newborn rabbits with and without exposure to inflammation in utero. We then used this model to analyze the dynamics of microglial migration and their interactions with dendrimers in the presence of neuroinflammation. Microglial cells in animals with CP had an amoeboid morphology and impaired cell migration, demonstrated by decreased migration distance and velocity when compared to cells in healthy, age-matched controls. However, this decreased migration was associated with a greater, more rapid dendrimer uptake compared to microglial cells from healthy controls. This study demonstrates that maternal intrauterine inflammation is associated with impaired microglial function and movement in the newborn brain. This microglial impairment may play a role in the development of ongoing brain injury and CP in the offspring. Increased uptake of dendrimers by the "impaired" microglia can be exploited to deliver drugs specifically to these cells and modulate their functions. Host tissue and target cell characteristics are important aspects to be considered in the design and evaluation of targeted dendrimer-based nanotherapeutics for improved and sustained efficacy. This ex

  19. Development of Tat-Conjugated Dendrimer for Transdermal DNA Vaccine Delivery.

    Science.gov (United States)

    Bahadoran, Azadeh; Moeini, Hassan; Bejo, Mohd Hair; Hussein, Mohd Zobir; Omar, Abdul Rahman

    In order to enhance cellular uptake and to facilitate transdermal delivery of DNA vaccine, polyamidoamine (PAMAM) dendrimers conjugated with HIV transactivator of transcription (TAT) was developed. First, the plasmid DNA (pIRES-H5/GFP) nanoparticle was formulated using PAMAM dendrimer and TAT peptide and then characterized for surface charge, particle size, DNA encapsulation and protection of the pIRES-H5/GFP DNA plasmid to enzymatic digestion. Subsequently, the potency of the TAT-conjugated dendrimer for gene delivery was evaluated through in vitro transfection into Vero cells followed by gene expression analysis including western blotting, fluorescent microscopy and PCR. The effect of the TAT peptide on cellular uptake of DNA vaccine was studied by qRT-PCR and flow cytometry. Finally, the ability of TAT-conjugated PAMAM dendrimer for transdermal delivery of the DNA plasmid was assessed through artificial membranes followed by qRT-PCR and flow cytometry. TAT-conjugated PAMAM dendrimer showed the ability to form a compact and nanometre-sized polyplexes with the plasmid DNA, having the size range of 105 to 115 nm and a positive charge of +42 to +45 mV over the N/P ratio of 6:1(+/-).  In vitro transfection analysis into Vero cells confirms the high potency of TAT-conjugated PAMAM dendrimer to enhance the cellular uptake of DNA vaccine.  The permeability value assay through artificial membranes reveals that TAT-conjugated PAMAM has more capacity for transdermal delivery of the DNA compared to unmodified PAMAM dendrimer (Pdendrimer is a promising non-viral vector for transdermal use.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  20. Prevention of Synaptic Alterations and Neurotoxic Effects of PAMAM Dendrimers by Surface Functionalization

    Directory of Open Access Journals (Sweden)

    Felipe Vidal

    2017-12-01

    Full Text Available One of the most studied nanocarriers for drug delivery are polyamidoamine (PAMAM dendrimers. However, the alterations produced by PAMAM dendrimers in neuronal function have not been thoroughly investigated, and important aspects such as effects on synaptic transmission remain unexplored. We focused on the neuronal activity disruption induced by dendrimers and the possibility to prevent these effects by surface chemical modifications. Therefore, we studied the effects of fourth generation PAMAM with unmodified positively charged surface (G4 in hippocampal neurons, and compared the results with dendrimers functionalized in 25% of their surface groups with folate (PFO25 and polyethylene glycol (PPEG25. G4 dendrimers significantly reduced cell viability at 1 µM, which was attenuated by both chemical modifications, PPEG25 being the less cytotoxic. Patch clamp recordings demonstrated that G4 induced a 7.5-fold increment in capacitive currents as a measure of membrane permeability. Moreover, treatment with this dendrimer increased intracellular Ca2+ by 8-fold with a complete disruption of transients pattern, having as consequence that G4 treatment increased the synaptic vesicle release and frequency of synaptic events by 2.4- and 3-fold, respectively. PFO25 and PPEG25 treatments did not alter membrane permeability, total Ca2+ intake, synaptic vesicle release or synaptic activity frequency. These results demonstrate that cationic G4 dendrimers have neurotoxic effects and induce alterations in normal synaptic activity, which are generated by the augmentation of membrane permeability and a subsequent intracellular Ca2+ increase. Interestingly, these toxic effects and synaptic alterations are prevented by the modification of 25% of PAMAM surface with either folate or polyethylene glycol.