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Sample records for cationic polyamidoamine dendrimer

  1. Cationic Polyamidoamine Dendrimers as Modulators of EGFR Signaling In Vitro and In Vivo.

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    Saghir Akhtar

    Full Text Available Cationic polyamidoamine (PAMAM dendrimers are branch-like spherical polymers being investigated for a variety of applications in nanomedicine including nucleic acid drug delivery. Emerging evidence suggests they exhibit intrinsic biological and toxicological effects but little is known of their interactions with signal transduction pathways. We previously showed that the activated (fragmented generation (G 6 PAMAM dendrimer, Superfect (SF, stimulated epidermal growth factor receptor (EGFR tyrosine kinase signaling-an important signaling cascade that regulates cell growth, survival and apoptosis- in cultured human embryonic kidney (HEK 293 cells. Here, we firstly studied the in vitro effects of Polyfect (PF, a non-activated (intact G6 PAMAM dendrimer, on EGFR tyrosine kinase signaling via extracellular-regulated kinase 1/2 (ERK1/2 and p38 mitogen-activated protein kinase (MAPK in cultured HEK 293 cells and then compared the in vivo effects of a single administration (10mg/kg i.p of PF or SF on EGFR signaling in the kidneys of normal and diabetic male Wistar rats. Polyfect exhibited a dose- and time-dependent inhibition of EGFR, ERK1/2 and p38 MAPK phosphorylation in HEK-293 cells similar to AG1478, a selective EGFR inhibitor. Administration of dendrimers to non-diabetic or diabetic animals for 24h showed that PF inhibited whereas SF stimulated EGFR phosphorylation in the kidneys of both sets of animals. PF-mediated inhibition of EGFR phosphorylation as well as SF or PF-mediated apoptosis in HEK 293 cells could be significantly reversed by co-treatment with antioxidants such as tempol implying that both these effects involved an oxidative stress-dependent mechanism. These results show for the first time that SF and PF PAMAM dendrimers can differentially modulate the important EGFR signal transduction pathway in vivo and may represent a novel class of EGFR modulators. These findings could have important clinical implications for the use of PAMAM

  2. Cationic Polyamidoamine Dendrimers as Modulators of EGFR Signaling In Vitro and In Vivo.

    Science.gov (United States)

    Akhtar, Saghir; Al-Zaid, Bashayer; El-Hashim, Ahmed Z; Chandrasekhar, Bindu; Attur, Sreeja; Yousif, Mariam H M; Benter, Ibrahim F

    2015-01-01

    Cationic polyamidoamine (PAMAM) dendrimers are branch-like spherical polymers being investigated for a variety of applications in nanomedicine including nucleic acid drug delivery. Emerging evidence suggests they exhibit intrinsic biological and toxicological effects but little is known of their interactions with signal transduction pathways. We previously showed that the activated (fragmented) generation (G) 6 PAMAM dendrimer, Superfect (SF), stimulated epidermal growth factor receptor (EGFR) tyrosine kinase signaling-an important signaling cascade that regulates cell growth, survival and apoptosis- in cultured human embryonic kidney (HEK 293) cells. Here, we firstly studied the in vitro effects of Polyfect (PF), a non-activated (intact) G6 PAMAM dendrimer, on EGFR tyrosine kinase signaling via extracellular-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) in cultured HEK 293 cells and then compared the in vivo effects of a single administration (10mg/kg i.p) of PF or SF on EGFR signaling in the kidneys of normal and diabetic male Wistar rats. Polyfect exhibited a dose- and time-dependent inhibition of EGFR, ERK1/2 and p38 MAPK phosphorylation in HEK-293 cells similar to AG1478, a selective EGFR inhibitor. Administration of dendrimers to non-diabetic or diabetic animals for 24h showed that PF inhibited whereas SF stimulated EGFR phosphorylation in the kidneys of both sets of animals. PF-mediated inhibition of EGFR phosphorylation as well as SF or PF-mediated apoptosis in HEK 293 cells could be significantly reversed by co-treatment with antioxidants such as tempol implying that both these effects involved an oxidative stress-dependent mechanism. These results show for the first time that SF and PF PAMAM dendrimers can differentially modulate the important EGFR signal transduction pathway in vivo and may represent a novel class of EGFR modulators. These findings could have important clinical implications for the use of PAMAM dendrimers

  3. Cationic poly(amidoamine) dendrimers induced cyto-protective autophagy in hepatocellular carcinoma cells

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    Li, Yubin; Wang, Shaofei; Wang, Ziyu; Qian, Xiaolu; Fan, Jiajun; Zeng, Xian; Sun, Yun; Song, Ping; Feng, Meiqing; Ju, Dianwen

    2014-09-01

    Poly(amidoamine) (PAMAM) dendrimers are proposed as one of the most promising nanomaterials for biomedical applications because of their unique tree-like structure, monodispersity and tunable properties. In this study, we found that PAMAM dendrimers could induce the formation of autophagosomes and the conversion of microtubule-associated protein 1 light chain 3 (LC3) in hepatocellular carcinoma HepG2 cells, while the inhibition of the Akt/mTOR and activation of the Erk 1/2 signaling pathways were involved in autophagy-induced by PAMAM dendrimers. We also investigated the suppression of autophagy with the obviously enhanced cytotoxicity of PAMAM dendrimers. Moreover, the blockage of a reactive oxygen species (ROS) could enhance the growth inhibition and apoptosis of hepatocellular carcinoma cells, induced by PAMAM dendrimers through reducing autophagic effects. Taken together, these findings explored the role and mechanism of autophagy induced by PAMAM dendrimers in HepG2 cells, provided new insight into the effect of autophagy on drug delivery nanomaterials and tumor cells and contributed to the use of a drug delivery vehicle for hepatocellular carcinoma treatment.

  4. The Effect of Cationic Polyamidoamine Dendrimers on Physicochemical Characteristics of Hydrogels with Erythromycin

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    Magdalena Wróblewska

    2015-08-01

    Full Text Available Polyamidoamine dendrimers (PAMAM represent a new class of hyperbranched, monodisperse, three-dimensional polymers with unique properties, which make them very promising carriers of antimicrobial agents. The present study aimed to evaluate the influence of PAMAM-NH2 dendrimers generation two (G2 or three (G3 on physicochemical characteristics and structure of hydrogels with a model antibacterial lipophilic drug—erythromycin—commonly used in topical applications. From the obtained rheograms, it can be concluded that tested hydrogels were non-Newtonian thixotropic systems with shear-thinning behaviour. The dissolution tests revealed that erythromycin was definitely faster released from formulations containing PAMAM-NH2 in concentration and generation dependent manner. However, the addition of PAMAM-NH2 to hydrogels evoked only slight improvement of their antibacterial activity. It was also shown that the structure of hydrogels changed in the presence of PAMAM-NH2 becoming less compact, diversified and more porous. Designed hydrogels with PAMAM-NH2 G2 or G3 were stable stored up to three months at 40 ± 2 °C and 75% ± 5% RH.

  5. The Effect of Cationic Polyamidoamine Dendrimers on Physicochemical Characteristics of Hydrogels with Erythromycin.

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    Wróblewska, Magdalena; Winnicka, Katarzyna

    2015-08-27

    Polyamidoamine dendrimers (PAMAM) represent a new class of hyperbranched, monodisperse, three-dimensional polymers with unique properties, which make them very promising carriers of antimicrobial agents. The present study aimed to evaluate the influence of PAMAM-NH₂ dendrimers generation two (G2) or three (G3) on physicochemical characteristics and structure of hydrogels with a model antibacterial lipophilic drug-erythromycin-commonly used in topical applications. From the obtained rheograms, it can be concluded that tested hydrogels were non-Newtonian thixotropic systems with shear-thinning behaviour. The dissolution tests revealed that erythromycin was definitely faster released from formulations containing PAMAM-NH₂ in concentration and generation dependent manner. However, the addition of PAMAM-NH₂ to hydrogels evoked only slight improvement of their antibacterial activity. It was also shown that the structure of hydrogels changed in the presence of PAMAM-NH₂ becoming less compact, diversified and more porous. Designed hydrogels with PAMAM-NH₂ G2 or G3 were stable stored up to three months at 40 ± 2 °C and 75% ± 5% RH.

  6. Electrospinning of PEGylated polyamidoamine dendrimer fibers.

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    Aduba, Donald C; Overlin, Jefferson W; Frierson, Chad D; Bowlin, Gary L; Yang, Hu

    2015-11-01

    Polyamidoamine (PAMAM) dendrimers have emerged as an important class of nanostructured materials and have found a broad range of applications. There is also an ongoing effort to synthesize higher-complexity structures using PAMAM dendrimers as enabling building blocks. Herein, we report for the first time the fabrication of electrospun nanocomposite fibers composed of dendrimer derivatives, namely PEGylated PAMAM dendrimers, blended with a small amount of high-molecular-weight polyethylene oxide (PEO). Morphological features and mechanical properties of the resulting dendrimer fiber mats were assessed. PMID:26249580

  7. Electrochemistry of polyamidoamine dendrimers ester gel electrolytes

    Institute of Scientific and Technical Information of China (English)

    CHEN Hong; MO Zunli

    2004-01-01

    This paper described the first example of polyamidoamine dendrimers ester (PAMAM) used as a gel electrolyte with a short-chain polyethylene glycol (MPEG-400) as a plasticizer. The polymer films are solid and sticky. Background cyclic voltammetry (CV) shows a potential window between +0.7 and -0.7 V vs. Ag/AgCl. The voltammetry of ferrocene and 7,7,8,8-tetracyanoquinodimethane (TCNQ) indicates that diffusion coefficients are in the range of 10-a-10-9 cm2/s.Ionic conductivities are approximately 10-6 S/cm. Similar films using dimethyl sulfoxide (DMSO) as a plasticizer instead of MPEG-400 have demonstrated ionic conductivities of 10-4 S/cra and reversible voltammetry. However, UV spectrophotometry shows that 70% of the DMSO is lost under vacuum, indicating the difficulty in quantifying the DMSO content when exposed to vacuum.

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

    International Nuclear Information System (INIS)

    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

  9. Surface conjugation of triphenylphosphonium to target poly(amidoamine) dendrimers to mitochondria

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    Biswas, Swati; Dodwadkar, Namita S.; Piroyan, Aleksandr; Torchilin, Vladimir P.

    2013-01-01

    Dendrimers have emerged as promising carriers for the delivery of a wide variety of pay-loads including therapeutic drugs, imaging agents and nucleic acid materials into biological systems. The current work aimed to develop a novel mitochondria-targeted generation 5 poly(amidoamine) (PAMAM) dendrimer (G(5)-D). To achieve this goal, a known mitochondriotropic ligand triphenylphosphonium (TPP) was conjugated on the surface of the dendrimer. A fraction of the cationic surface charge of G(5)-D was neutralized by partial acetylation of the primary amine groups. Next, the mitochondria-targeted dendrimer was synthesized via the acid-amine-coupling conjugation reaction between the acid group of (3-carboxypropyl)triphenyl-phosphonium bromide and the primary amines of the acetylated dendrimer (G(5)-D-Ac). These dendrimers were fluorescently labeled with fluorescein isothiocyanate (FITC) to quantify cell association by flow cytometry and for visualization under confocal laser scanning microscopy to assess the mitochondrial targeting in vitro. The newly developed TPP-anchored dendrimer (G(5)-D-Ac-TPP) was efficiently taken up by the cells and demonstrated good mitochondrial targeting. In vitro cytotoxicity experiments carried out on normal mouse fibroblast cells (NIH-3T3) had greater cell viability in the presence of the G(5)-D-Ac-TPP compared to the parent unmodified G(5)-D. This mitochondriatargeted dendrimer-based nanocarrier could be useful for imaging as well as for selective delivery of bio-actives to the mitochondria for the treatment of diseases associated with mitochondrial dysfunction. PMID:22469294

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

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    Shao N

    2011-12-01

    Full Text Available Naimin Shao1, Yunzhang Su1, Jingjing Hu2, Jiahai Zhang3, Hongfeng Zhang1, Yiyun Cheng1,41School of Life Sciences, East China Normal University, Shanghai, 2CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China, Hefei,  3School of Life Sciences, University of Science and Technology of China, Hefei, 4Shanghai Key Laboratory of Magnetic Resonance, Department of Physics, East China Normal University, Shanghai, ChinaBackground: 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.Keywords: dendrimer, polyamidoamine, polypropylenimine, drug delivery, cytotoxicity

  11. Rendering poly(amidoamine) or poly(propylenimine) dendrimers temperature sensitive.

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    Haba, Yasuhiro; Harada, Atsushi; Takagishi, Toru; Kono, Kenji

    2004-10-13

    The poly(amidoamine) dendrimers having terminal isobutyramide (IBAM) groups were prepared by the reaction of isobutyric acid and the amine-terminated poly(amidoamine) dendrimers with generations (G) of 2 to 5 by using a condensing agent, 1,3-dicyclohexylcarbodiimide. 1H and 13C NMR revealed that an IBAM group was attached to essentially every chain end of the dendrimers. While the IBAM-terminated G2 dendrimer was soluble in water, the IBAM-terminated G3, G4, and G5 dendrimers exhibited the lower critical solution temperatures (LCSTs) at 75, 61, and 43 degrees C, respectively. Because the density of the terminal IBAM groups in the periphery of the dendrimer progressively increases with increasing dendrimer generation, the interaction of the IBAM groups might take place more efficiently, resulting in a remarkable decrease in the LCST. In addition, attachment of IBAM groups to poly(propylenimine) dendrimers could give the temperature-sensitive property, indicating that this is an efficient method to render dendrimers temperature sensitive.

  12. 9-Anthracenecarboxaldehyde Functionalized Second Generation Poly(amidoamine) Dendrimers: Synthesis and Metal Absorption

    Institute of Scientific and Technical Information of China (English)

    Xu Min HE; Wei ZHENG; Pei Xie YANG; Hai Ping XIA

    2006-01-01

    In this paper we report the peripheral functionalization of amine-terminated second generation poly(amidoamine) (PAMAM) with 9-anthracenecarboxalehyde and the preparation of dendrimer-encapsulated metal salts. The interesting different behaviors of these hybrid materials were observed by fluorescence and UV-Vis spectra.

  13. Encapsulation of 2-methoxyestradiol within multifunctional poly(amidoamine) dendrimers for targeted cancer therapy.

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    Wang, Yin; Guo, Rui; Cao, Xueyan; Shen, Mingwu; Shi, Xiangyang

    2011-04-01

    We report here a general approach to using multifunctional poly(amidoamine) (PAMAM) dendrimer-based platform to encapsulate a potential anticancer drug for targeted cancer therapy. In this approach, amine-terminated generation 5 (G5) PAMAM dendrimers were sequentially modified with fluorescein isothiocyanate (FI) and folic acid (FA) via covalent conjugation, followed by an acetylation reaction to neutralize the remaining amines of the dendrimer surfaces. The synthesized multifunctional dendrimers (G5.NHAc-FI-FA) were then used to complex a potential anticancer drug, 2-methoxyestradiol (2-ME) for targeted delivery of the drugs to cancer cells overexpressing high-affinity folic acid receptors (FAR). We show that the formed G5.NHAc-FI-FA/2-ME complexes with each dendrimer encapsulating approximately 3.7 2-ME molecules are water soluble and stable. In vitro release studies show that 2-ME complexed with the multifunctional dendrimers can be released in a sustained manner. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in conjunction with cell morphology observation demonstrates that the G5.NHAc-FI-FA/2-ME complexes can specifically target and display specific therapeutic efficacy to cancer cells overexpressing high-affinity FAR. Findings from this study suggest that multifunctional dendrimers may be used as a general drug carrier to encapsulate various cancer drugs for targeted therapy of different types of cancer.

  14. Naked Polyamidoamine Polymers Intrinsically Inhibit Angiotensin II-Mediated EGFR and ErbB2 Transactivation in a Dendrimer Generation- and Surface Chemistry-Dependent Manner.

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    Akhtar, Saghir; El-Hashim, Ahmed Z; Chandrasekhar, Bindu; Attur, Sreeja; Benter, Ibrahim F

    2016-05-01

    The effects of naked polyamidoamine (PAMAM) dendrimers on renin-angiotensin system (RAS) signaling via Angiotensin (Ang) II-mediated transactivation of the epidermal growth factor receptor (EGFR) and the closely related family member ErbB2 (HER2) were investigated. In primary aortic vascular smooth muscle cells, a cationic fifth-generation (G5) PAMAM dendrimer dose- and time-dependently inhibited Ang II/AT1 receptor-mediated transactivation of EGFR and ErbB2 as well as their downstream signaling via extracellular-regulated kinase 1/2 (ERK1/2). Inhibition even occurred at noncytotoxic concentrations at short (1 h) exposure times and was dependent on dendrimer generation (G7 > G6 > G5 > G4) and surface group chemistry (amino > carboxyl > hydroxyl). Mechanistically, the cationic G5 PAMAM dendrimer inhibited Ang II-mediated transactivation of EGFR and ErbB2 via inhibition of the nonreceptor tyrosine kinase Src. This novel, early onset, intrinsic biological action of PAMAM dendrimers as inhibitors of the Ang II/AT1/Src/EGFR-ErbB2/ERK1/2 signaling pathway could have important toxicological and pharmacological implications.

  15. Intermolecular forces between low generation PAMAM dendrimer condensed DNA helices: role of cation architecture.

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    An, Min; Parkin, Sean R; DeRouchey, Jason E

    2014-01-28

    In recent years, dendriplexes, complexes of cationic dendrimers with DNA, have become attractive DNA delivery vehicles due to their well-defined chemistries. To better understand the nature of the forces condensing dendriplexes, we studied low generation poly(amidoamine) (PAMAM) dendrimer-DNA complexes and compared them to comparably charged linear arginine peptides. Using osmotic stress coupled with X-ray scattering, we have investigated the effect of molecular chain architecture on DNA-DNA intermolecular forces that determine the net attraction and equilibrium interhelical distance within these polycation condensed DNA arrays. In order to compact DNA, linear cations are believed to bind in DNA grooves and to interact with the phosphate backbone of apposing helices. We have previously shown a length dependent attraction resulting in higher packaging densities with increasing charge for linear cations. Hyperbranched polycations, such as polycationic dendrimers, presumably would not be able to bind to DNA and correlate their charges in the same manner as linear cations. We show that attractive and repulsive force amplitudes in PAMAM-DNA assemblies display significantly different trends than comparably charged linear arginines resulting in lower DNA packaging densities with increasing PAMAM generation. The salt and pH dependencies of packaging in PAMAM dendrimer-DNA and linear arginine-DNA complexes were also investigated. Significant differences in the force curve behaviour and salt and pH sensitivities suggest that different binding modes may be present in DNA condensed by dendrimers when compared to linear polycations. PMID:24651934

  16. Polyamidoamine dendrimer and oleic acid-functionalized graphene as biocompatible and efficient gene delivery vectors.

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    Liu, Xiahui; Ma, Dongmei; Tang, Hao; Tan, Liang; Xie, Qingji; Zhang, Youyu; Ma, Ming; Yao, Shouzhuo

    2014-06-11

    Functionalized graphene has good potential in biomedical applications. To address a better and multiplex design of graphene-based gene vectors, the graphene-oleate-polyamidoamine (PAMAM) dendrimer hybrids were synthesized by the oleic acid adsorption and covalent linkage of PAMAM dendrimers. The micromorphology, electrical charge property, and amount of free amine groups of the graphene-oleate-PAMAM hybrids were characterized, and the peripheral functional groups were identified. The PAMAM dendrimers could be tethered onto graphene surface in high density. The graphene-oleate-PAMAM hybrids exhibit relatively good dispersity and stability in aqueous solutions. To evaluate the potential application of the hybrids in gene delivery vectors, cytotoxicity to HeLa and MG-63 cells and gene (plasmid DNA of enhanced green fluorescent protein) transfection capacity of the hybrids were investigated in detail. The graphene-oleate-PAMAM hybrids show mammalian cell type- and dose-dependent in vitro cytotoxicity. Under the optimal condition, the hybrids possess good biocompatibility and gene transfection capacity. The surface modification of graphene with oleic acid and PAMAM improves the gene transfection efficiency 13 times in contrast to the ultrasonicated graphene. Moreover, the hybrids show better transfection efficiency than the graphene oxide-PAMAM without the oleic acid modification. PMID:24836601

  17. Nano polyamidoamine-G7 dendrimer synthesis and assessment the antibacterial effect in vitro

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    Mitra Gholami

    2016-04-01

    Full Text Available Background: Nano scale dendrimers are macromolecules synthetic which frequently used in medical and health field. Because traditional antibiotics inevitably induce bacterial resistance, which is responsible for many treatment failures, there is an urgent need to develop novel antibiotic drugs. This study was aimed to examine Synthesis and the antibacterial effect of NanoPolyamidoamine-G7 (NPAMAM-G7 dendrimer on Escherichia Coli, Proteus Mirabilis, Salmonella Typhi, Bacillus Subtilis and Staphylococcus Aureus. Methods: In this experimental study that has been conducted in June 2015 in the Laboratory of Microbiology, Iran University of Medical Science, NPAMAM-G7 dendrimers was synthesized by Tomalia’s divergent growth approach. The antibacterial effects of NPAMAM-G7 dendrimer were studied by disc diffusion and micro-dilution method. Minimum inhibitory concentration (MIC and minimum bactericidal concentration (MBC against gram-positive and gram-negative bacteria were determined according to Clinical and Laboratory Standards Institute (CLSI guideline. Standard discs were prepared using different concentrations of dendrimer on Mueller-Hinton agar plates. Results: Zone of inhibition in concentration 25 μg/ml of NPAMAM-G7 dendrimers for Escherichia Coli, Proteus Mirabilis, Salmonella Typhi, Bacillus Subtilis and Staphylococcus Aureus were 26, 38, 36, 22 and 25 mm, respectively. Regarding the zone of inhibition in gram negative bacteria with gram positive ones was P= 0.16 and was not significant difference. The MIC for Salmonella Typhi was 0.025, for Proteus Mirabilis, Bacillus Subtilis, Staphylococcus Aureus and Escherichia Coli was 0.25 μg/ml. The MBC for Salmonella Typhi was 25μg/ml, for Proteus Mirabilis and Bacillus Subtilis was 50 μg/ml and for Escherichia Coli and Staphylococcus Aureus was 100 μg/ml. The least of sensitivity against NPAMAM-G7 related to Escherichia Coli and Staphylococcus Aureus and the most of sensitivity related to

  18. Interaction Mechanism of Nano-silicon Dioxide Modified by Poly(amidoamine) Dendrimers

    Institute of Scientific and Technical Information of China (English)

    Tao Jin; Xiao-yu Li

    2012-01-01

    To gain insight into the attachment of ≡Si+ (SC) ion (regarded as guest) to the lowest generation,NH2-terminated poly(amidoamine) (PAMAM) dendrimers (regarded as host) in the liquid phase,density functional theory is used to investigate the structures and energetics of the host-guest complex.The effect of solvent on the structures and energetics is also investigated.Various initial configurations of the ion bound to PAMAM are tested,and two stable conformers are found,i.e,types A (≡Si+ is bound to the amine site) and C (≡Si+ is bound to the amide site).Types A and C are the most stable due to the chemical bond formations of Si-No (amine nitrogen atoms) and Si-O,respectively.The IR spectra for the lowest energy conformers are thoroughly analyzed and compared with the available experimental data.

  19. Single-Walled Carbon Nanotube-Polyamidoamine Dendrimer Hybrids for Heterogeneous Catalysis.

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    Giacalone, Francesco; Campisciano, Vincenzo; Calabrese, Carla; La Parola, Valeria; Syrgiannis, Zois; Prato, Maurizio; Gruttadauria, Michelangelo

    2016-04-26

    We report the synthesis and catalytic properties of single-walled carbon nanotube-polyamidoamine dendrimers hybrids (SWCNT-PAMAM), prepared via a convergent strategy. The direct reaction of cystamine-based PAMAM dendrimers (generations 2.5 and 3.0) with pristine SWCNTs in refluxing toluene, followed by immobilization and reduction of [PdCl4](2-), led to the formation of highly dispersed small palladium nanoparticles homogeneously confined throughout the nanotube length. One of these functional materials proved to be an efficient catalyst in Suzuki and Heck reactions, able to promote the above processes down to 0.002 mol % showing a turnover number (TON) of 48 000 and a turnover frequency (TOF) of 566 000 h(-1). In addition, the hybrid material could be recovered and recycled for up to 6 times. No leaching of the metal has been detected during the Suzuki coupling. Additional experiments carried out on the spent catalyst permitted to suggest that a "release and catch" mechanism is operative in both reactions, although during Heck reaction small catalytically active soluble Pd species are also present.

  20. The cellular uptake mechanism, intracellular transportation, and exocytosis of polyamidoamine dendrimers in multidrug-resistant breast cancer cells

    OpenAIRE

    Zhang, Jie; Liu, Dan; Zhang,Mengjun; Sun,Yuqi; Zhang, Xiaojun; Guan,Guannan; Zhao, Xiuli; Qiao,Mingxi; Chen, Dawei; Hu, Haiyang

    2016-01-01

    Jie Zhang,1 Dan Liu,1 Mengjun Zhang,1 Yuqi Sun,1,2 Xiaojun Zhang,1 Guannan Guan,1 Xiuli Zhao,1 Mingxi Qiao,1 Dawei Chen,1 Haiyang Hu1 1Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 2Department of Pharmaceutics, School of Pharmacy, Liaoning Medical University, Jinzhou, Liaoning Province, People’s Republic of China Abstract: Polyamidoamine dendrimers, which can deliver drugs and genetic materials to resistant cells, are attracting inc...

  1. Evaluation of cationic polyamidoamine dendrimers’ dermal toxicity in the rat skin model

    Directory of Open Access Journals (Sweden)

    Winnicka K

    2015-03-01

    Full Text Available Katarzyna Winnicka,1 Magdalena Wroblewska,1 Katarzyna Sosnowska,1 Halina Car,2 Irena Kasacka3 1Department of Pharmaceutical Technology, Faculty of Pharmacy, Medical University of Bialystok, Bialystok, Poland; 2Department of Experimental Pharmacology, Faculty of Health Sciences, Medical University of Bialystok, Bialystok, Poland; 3Department of Histology and Cytophysiology, Faculty of Pharmacy, Medical University of Bialystok, Bialystok, Poland Abstract: Polyamidoamine (PAMAM dendrimers are multi-branched, three-dimensional polymers with unique architecture, which makes these molecules attractive for medical and pharmaceutical applications. Using PAMAM as drug carriers for topical delivery might be beneficial as they only produce a transient effect without skin irritation. To evaluate the dermal toxicity of cationic PAMAM dendrimers generation 2 and generation 3, skin irritation studies were performed in vivo in the rat skin model. After 10 days topical application of various concentrations of PAMAM-NH2 (0.3 mg/mL, 3 mg/mL, 6 mg/mL, 30 mg/mL, 300 mg/mL, skin irritation was evaluated by visual, histopathological, and immunohistochemical examination. Microscopic assessment after hematoxylin-eosin staining revealed significant morphological changes of epidermal cells after application of PAMAM-NH2 at a concentration of ≥6 mg/mL. Morphological alterations of epidermal cells included cytoplasmic vacuolization of keratinocytes in the basal and spinous layers. Cytomorphological changes in keratinocytes, overall picture of the epidermis, and histopathological changes in the dermis were dose dependent. Detected alterations concerned hyperplasia of connective tissue fibers and leukocyte infiltration. Visible granulocyte infiltration in the upper dermis and sockets formed by necrotic, cornified cells in the hyperplastic foci of epithelium were also noted. Immunohistochemical analyses revealed that increased nuclear immunoreactivity to PCNA correlated with

  2. Polyamidoamine Dendrimer Conjugates with Cyclodextrins as Novel Carriers for DNA, shRNA and siRNA

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    Hidetoshi Arima

    2012-02-01

    Full Text Available Gene, short hairpin RNA (shRNA and small interfering RNA (siRNA delivery can be particularly used for the treatment of diseases by the entry of genetic materials mammalian cells either to express new proteins or to suppress the expression of proteins, respectively. Polyamidoamine (PAMAM StarburstTM dendrimers are used as non-viral vectors (carriers for gene, shRNA and siRNA delivery. Recently, multifunctional PAMAM dendrimers can be used for the wide range of biomedical applications including intracellular delivery of genes and nucleic acid drugs. In this context, this review paper provides the recent findings on PAMAM dendrimer conjugates with cyclodextrins (CyDs for gene, shRNA and siRNA delivery.

  3. Anti-Biofilm Efficacy of Dual-Action Nitric Oxide-Releasing Alkyl Chain Modified Poly(amidoamine) Dendrimers.

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    Worley, Brittany V; Schilly, Kelci M; Schoenfisch, Mark H

    2015-05-01

    Herein, we describe the synthesis of nitric oxide (NO)-releasing alkyl chain modified poly(amidoamine) (PAMAM) dendrimers of various sizes (i.e., generations). Generation 1 (G1) through generation 4 (G4) dendrimers were modified with either short (i.e., butyl) or medium (i.e., hexyl) alkyl chains via a ring-opening reaction. The resulting secondary amines were subsequently modified with N-diazeniumdiolate NO donors to establish NO payloads of ∼1.0 μmol/mg. The bactericidal efficacy of these dendrimers was evaluated against Gram-negative and Gram-positive biofilms, including antibiotic-resistant strains. The anti-biofilm action of the dendrimer biocides was found to be dependent on dendrimer generation, bacterial Gram class, and alkyl chain length, with the most effective biofilm eradication occurring when antibacterial agents were capable of efficient biofilm infiltration. The addition of NO release markedly enhanced anti-biofilm activity of dendrimers incapable of effective biofilm penetration. PMID:25873449

  4. Electrochemical functionalization of polypyrrole through amine oxidation of poly(amidoamine) dendrimers: Application to DNA biosensor.

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    Miodek, Anna; Mejri-Omrani, Nawel; Khoder, Rabih; Korri-Youssoufi, Hafsa

    2016-07-01

    Electrochemical patterning method has been developed to fabricate composite based on polypyrrole (PPy) film and poly(amidoamine) dendrimers of fourth generation (PAMAM G4). PPy layer was generated using electrochemical polymerization of pyrrole on a gold electrode. PPy film was then modified with PAMAM G4 using amines electro-oxidation method. Covalent bonding of PAMAM G4 and the formation of PPy-PAMAM composite was characterized using Fourier Transform Infrared Spectroscopy (FT-IR) and X-ray Photoelectron Spectroscopy (XPS). Ferrocenyl groups were then attached to such surface as a redox marker. Electrochemical properties of the modified nanomaterial (PPy-PAMAM-Fc) were studied using both amperometric and impedimetric methods to demonstrate the efficiency of electron transfer through the modified PPy layer. The obtained electrical and electrochemical properties were compared to a composite where PPy bearing carboxylic acid functions was chemically modified with PAMAM G4 by covalent attachment through formation of amid bond (PPy-CONH-PAMAM). The above mentioned studies showed that electrochemical patterning does not disturb the electronic properties of PPy. The effect of the number of functional groups introduced by the electrochemical patterning was demonstrated through the association of various compounds (ethylenediamine, PAMAM G2 and PAMAM G6). We demonstrated that such compounds could be applied in the biosensors technology. The modified PPy-PAMAM-Fc was evaluated as a platform for DNA sensing. High performance in the DNA detection by variation of the electrochemical signal of ferrocene was obtained with detection limit of 0.4 fM. Furthermore, such approach of electrochemical patterning by oxidation of amines could be applied for chemical modification of PPy and open a new way in various biosensing application involving functionalized PPy. PMID:27154698

  5. Electrochemical functionalization of polypyrrole through amine oxidation of poly(amidoamine) dendrimers: Application to DNA biosensor.

    Science.gov (United States)

    Miodek, Anna; Mejri-Omrani, Nawel; Khoder, Rabih; Korri-Youssoufi, Hafsa

    2016-07-01

    Electrochemical patterning method has been developed to fabricate composite based on polypyrrole (PPy) film and poly(amidoamine) dendrimers of fourth generation (PAMAM G4). PPy layer was generated using electrochemical polymerization of pyrrole on a gold electrode. PPy film was then modified with PAMAM G4 using amines electro-oxidation method. Covalent bonding of PAMAM G4 and the formation of PPy-PAMAM composite was characterized using Fourier Transform Infrared Spectroscopy (FT-IR) and X-ray Photoelectron Spectroscopy (XPS). Ferrocenyl groups were then attached to such surface as a redox marker. Electrochemical properties of the modified nanomaterial (PPy-PAMAM-Fc) were studied using both amperometric and impedimetric methods to demonstrate the efficiency of electron transfer through the modified PPy layer. The obtained electrical and electrochemical properties were compared to a composite where PPy bearing carboxylic acid functions was chemically modified with PAMAM G4 by covalent attachment through formation of amid bond (PPy-CONH-PAMAM). The above mentioned studies showed that electrochemical patterning does not disturb the electronic properties of PPy. The effect of the number of functional groups introduced by the electrochemical patterning was demonstrated through the association of various compounds (ethylenediamine, PAMAM G2 and PAMAM G6). We demonstrated that such compounds could be applied in the biosensors technology. The modified PPy-PAMAM-Fc was evaluated as a platform for DNA sensing. High performance in the DNA detection by variation of the electrochemical signal of ferrocene was obtained with detection limit of 0.4 fM. Furthermore, such approach of electrochemical patterning by oxidation of amines could be applied for chemical modification of PPy and open a new way in various biosensing application involving functionalized PPy.

  6. Differences in toxicity of anionic and cationic PAMAM and PPI dendrimers in zebrafish embryos and cancer cell lines.

    Science.gov (United States)

    Bodewein, Lambert; Schmelter, Frank; Di Fiore, Stefano; Hollert, Henner; Fischer, Rainer; Fenske, Martina

    2016-08-15

    Dendrimers are an emerging class of polymeric nanoparticles with beneficial biomedical applications like early diagnostics, in vitro gene transfection or controlled drug delivery. However, the potential toxic impact of exposure on human health or the environment is often inadequately defined. Thus, polyamidoamine (PAMAM) dendrimers of generations G3.0, 3.5, 4.0, 4.5 and 5.0 and polypropylenimine (PPI) dendrimers G3.0, 4.0 and 5.0 were tested in zebrafish embryos for 96h and human cancer cell lines for 24h, to assess and compare developmental in vivo toxicity with cytotoxicity. The zebrafish embryo toxicity of cationic PAMAM and PPI dendrimers increased over time, with EC50 values ranging from 0.16 to just below 1.7μM at 24 and 48hpf. The predominant effects were mortality, plus reduced heartbeat and blood circulation for PPI dendrimers. Apoptosis in the embryos increased in line with the general toxicity concentration-dependently. Hatch and dechorionation of the embryos increased the toxicity, suggesting a protective role of the chorion. Lower generation dendrimers were more toxic in the embryos whereas the toxicity in the HepG2 and DU145 cell lines increased with increasing generation of cationic PAMAMs and PPI dendrimers. HepG2 were less sensitive than DU145 cells, with IC50 values≥402μM (PAMAMs) and ≤240μM (PPIs) for HepG2 and ≤13.24μM (PAMAMs) and ≤12.84μM (PPIs) for DU145. Neither in fish embryos nor cells toxicity thresholds were determinable for anionic PAMAM G3.5 and G4.5. The study demonstrated that the cytotoxicity underestimated the in-vivo toxicity of the dendrimers in the fish embryos. PMID:27288734

  7. Plasmid pORF-hTRAIL targeting to glioma using transferrin-modified polyamidoamine dendrimer

    Directory of Open Access Journals (Sweden)

    Gao S

    2015-12-01

    Full Text Available Song Gao,1,* Jianfeng Li,2 Chen Jiang,2 Bo Hong,3 Bing Hao4,* 1Department of Clinical Laboratory, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 2Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 3Department of Pathology, The Second Affiliated Hospital, 4Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: A gene drug delivery system for glioma therapy based on transferrin (Tf-modified polyamidoamine dendrimer (PAMAM was prepared. Gene drug, tumor necrosis factor-related apoptosis-inducing ligand (hTRAIL-encoding plasmid open reading frame (pORF-hTRAIL, Trail, was condensed by Tf-modified PAMAM to form nanoparticles (NPs. PAMAM-PEG-Tf/DNA NPs showed higher cellular uptake, in vitro gene expression, and cytotoxicity than PAMAM-PEG/DNA NPs in C6 cells. The in vivo targeting efficacy of NPs was visualized by ex vivo fluorescence imaging. Tf-modified NPs showed obvious glioma-targeting trend. Plasmid encoding green fluorescence protein (GFP was also condensed by modified or unmodified PAMAM to evaluate the in vivo gene expression level. The PAMAM-PEG-Tf/plasmid encoding enhanced green fluorescence protein (pEGFP NPs exhibited higher GFP expression level than PAMAM-PEG/pEGFP NPs. TUNEL assay revealed that Tf-modified NPs could induce much more tumor apoptosis. The median survival time of PAMAM-PEG-Tf/Trail-treated rats (28.5 days was longer than that of rats treated with PAMAM-PEG/Trail (25.5 days, temozolomide (24.5 days, PAMAM-PEG-Tf/pEGFP (19 days, or saline (17 days. The therapeutic effect was further confirmed by magnetic resonance imaging. This study demonstrated that targeting gene delivery system had potential application for the

  8. Characterization of Folic Acid and Poly(amidoamine) Dendrimer Interactions with Folate Binding Protein: A Force-Pulling Study.

    Science.gov (United States)

    Leroueil, Pascale R; DiMaggio, Stassi; Leistra, Abigail N; Blanchette, Craig D; Orme, Christine; Sinniah, Kumar; Orr, Bradford G; Banaszak Holl, Mark M

    2015-09-01

    Atomic force microscopy force-pulling experiments have been used to measure the binding forces between folic acid (FA) conjugated poly(amidoamine) (PAMAM) dendrimers and folate binding protein (FBP). The generation 5 (G5) PAMAM conjugates contained an average of 2.7, 4.7, and 7.2 FA per dendrimer. The most probable rupture force was measured to be 83, 201, and 189 pN for G5-FA2.7, G5-FA4.7, and G5-FA7.2, respectively. Folic acid blocking experiments for G5-FA7.2 reduced the frequency of successful binding events and increased the magnitude of the average rupture force to 274 pN. The force data are interpreted as arising from a network of van der Waals and electrostatic interactions that form between FBP and G5 PAMAM dendrimer, resulting in a binding strength far greater than that expected for an interaction between FA and FBP alone.

  9. Effect of the Route of Administration and PEGylation of Poly(amidoamine) Dendrimers on Their Systemic and Lung Cellular Biodistribution.

    Science.gov (United States)

    Zhong, Qian; Merkel, Olivia M; Reineke, Joshua J; da Rocha, Sandro R P

    2016-06-01

    There are many opportunities in the development of oral inhalation (oi) formulations for the delivery of small molecule therapeutics and biologics to and through the lungs. Nanocarriers have the potential to play a key role in advancing oi technologies and pushing the boundary of the pulmonary delivery market. In this work we investigate the effect of the route of administration and PEGylation on the systemic and lung cellular biodistribution of generation 3, amino-terminated poly(amidoamine) (PAMAM) dendrimers (G3NH2). Pharmacokinetic profiles show that the dendrimers reach their peak concentration in systemic circulation within a few hours after pulmonary delivery, independent of their chemistry (PEGylated or not), charge (+24 mV for G3NH2 vs -3.7 mV for G3NH2-24PEG1000), or size (5.1 nm for G3NH2 and 9.9 nm for G3NH2-24PEG1000). However, high density of surface modification with PEG enhances pulmonary absorption and the peak plasma concentration upon pulmonary delivery. The route of administration and PEGylation also significantly impact the whole body and local (lung cellular) distribution of the dendrimers. While ca. 83% of G3NH2 is found in the lungs upon pulmonary delivery at 6.5 h post administration, only 2% reached the lungs upon intravenous (iv) delivery. Moreover, no measurable concentration of either G3NH2 or G3NH2-24PEG1000 is found in the lymph nodes upon iv administration, while these are the tissues with the second highest mass distribution of dendrimers post pulmonary delivery. Dendrimer chemistry also significantly impacts the (cellular) distribution of the nanocarriers in the lung tissue. Upon pulmonary delivery, approximately 20% of the lung endothelial cells are seen to internalize G3NH2-24PEG1000, compared to only 6% for G3NH2. Conversely, G3NH2 is more readily taken up by lung epithelial cells (35%) when compared to its PEGylated counterpart (24%). The results shown here suggest that both the pulmonary route of administration and dendrimer

  10. Surface Hydrophobic Modification of Fifth-Generation Hydroxyl-Terminated Poly(amidoamine Dendrimers and Its Effect on Biocompatibility and Rheology

    Directory of Open Access Journals (Sweden)

    Paul D. Hamilton

    2009-08-01

    Full Text Available Water-soluble, commercially-available poly(amidoamine (PAMAM dendrimers are highly-branched, well-defined, monodisperse macromolecules having an ethylenediamine core and varying surface functional groups. Dendrimers are being employed in an increasing number of biomedical applications. In this study, commercially obtained generation 5 hydroxyl-terminated (G5OH PAMAM dendrimers were studied as potential proteomimetics for ophthalmic uses. To this end, the surface of G5OH PAMAM dendrimers were hydrophobically modified with varying amounts of dodecyl moieties, (flexible long aliphatic chains, or cholesteryl moieties (rigid lipid found in abundance in biological systems. Dendrimers were characterized by 1H-NMR, DLS, DSC and HPLC. The hydrophobic modification caused aggregation and molecular interactions between dendrimers that is absent in unmodified dendrimers. In vitro tissue culture showed that increasing the amount of dodecyl modification gave a proportional increase in toxicity of the dendrimers, while with increasing cholesteryl modification there was no corresponding increase in toxicity. Storage and loss modulus were measured for selected formulations. The hydrophobic modification caused an increase in loss modulus, while the effect on storage modulus was more complex. Rheological properties of the dendrimer solutions were comparable to those of porcine lens crystallins.

  11. The cellular uptake mechanism, intracellular transportation, and exocytosis of polyamidoamine dendrimers in multidrug-resistant breast cancer cells.

    Science.gov (United States)

    Zhang, Jie; Liu, Dan; Zhang, Mengjun; Sun, Yuqi; Zhang, Xiaojun; Guan, Guannan; Zhao, Xiuli; Qiao, Mingxi; Chen, Dawei; Hu, Haiyang

    2016-01-01

    Polyamidoamine dendrimers, which can deliver drugs and genetic materials to resistant cells, are attracting increased research attention, but their transportation behavior in resistant cells remains unclear. In this paper, we performed a systematic analysis of the cellular uptake, intracellular transportation, and efflux of PAMAM-NH2 dendrimers in multidrug-resistant breast cancer cells (MCF-7/ADR cells) using sensitive breast cancer cells (MCF-7 cells) as the control. We found that the uptake rate of PAMAM-NH2 was much lower and exocytosis of PAMAM-NH2 was much greater in MCF-7/ADR cells than in MCF-7 cells due to the elimination of PAMAM-NH2 from P-glycoprotein and the multidrug resistance-associated protein in MCF-7/ADR cells. Macropinocytosis played a more important role in its uptake in MCF-7/ADR cells than in MCF-7 cells. PAMAM-NH2 aggregated and became more degraded in the lysosomal vesicles of the MCF-7/ADR cells than in those of the MCF-7 cells. The endoplasmic reticulum and Golgi complex were found to participate in the exocytosis rather than endocytosis process of PAMAM-NH2 in both types of cells. Our findings clearly showed the intracellular transportation process of PAMAM-NH2 in MCF-7/ADR cells and provided a guide of using PAMAM-NH2 as a drug and gene vector in resistant cells. PMID:27536106

  12. Arginine-glycine-aspartic acid-polyethylene glycol-polyamidoamine dendrimer conjugate improves liver-cell aggregation and function in 3-D spheroid culture.

    Science.gov (United States)

    Chen, Zhanfei; Lian, Fen; Wang, Xiaoqian; Chen, Yanling; Tang, Nanhong

    2016-01-01

    The polyamidoamine (PAMAM) dendrimer, a type of macromolecule material, has been used in spheroidal cell culture and drug delivery in recent years. However, PAMAM is not involved in the study of hepatic cell-spheroid culture or its biological activity, particularly in detoxification function. Here, we constructed a PAMAM-dendrimer conjugate decorated by an integrin ligand: arginine-glycine-aspartic acid (RGD) peptide. Our studies demonstrate that RGD-polyethylene glycol (PEG)-PAMAM conjugates can promote singly floating hepatic cells to aggregate together in a sphere-like growth with a weak reactive oxygen species. Moreover, RGD-PEG-PAMAM conjugates can activate the AKT-MAPK pathway in hepatic cells to promote cell proliferation and improve basic function and ammonia metabolism. Together, our data support the hepatocyte sphere treated by RGD-PEG-PAMAM conjugates as a potential source of hepatic cells for a biological artificial liver system. PMID:27621619

  13. Arginine–glycine–aspartic acid–polyethylene glycol–polyamidoamine dendrimer conjugate improves liver-cell aggregation and function in 3-D spheroid culture

    Science.gov (United States)

    Chen, Zhanfei; Lian, Fen; Wang, Xiaoqian; Chen, Yanling; Tang, Nanhong

    2016-01-01

    The polyamidoamine (PAMAM) dendrimer, a type of macromolecule material, has been used in spheroidal cell culture and drug delivery in recent years. However, PAMAM is not involved in the study of hepatic cell-spheroid culture or its biological activity, particularly in detoxification function. Here, we constructed a PAMAM-dendrimer conjugate decorated by an integrin ligand: arginine–glycine–aspartic acid (RGD) peptide. Our studies demonstrate that RGD–polyethylene glycol (PEG)–PAMAM conjugates can promote singly floating hepatic cells to aggregate together in a sphere-like growth with a weak reactive oxygen species. Moreover, RGD-PEG-PAMAM conjugates can activate the AKT–MAPK pathway in hepatic cells to promote cell proliferation and improve basic function and ammonia metabolism. Together, our data support the hepatocyte sphere treated by RGD-PEG-PAMAM conjugates as a potential source of hepatic cells for a biological artificial liver system. PMID:27621619

  14. Poly(amidoamine) Dendrimer Nanocarriers and Their Aerosol Formulations for siRNA Delivery to the Lung Epithelium

    Science.gov (United States)

    2015-01-01

    Small interfering RNA (siRNA)-based therapies have great promise in the treatment of a number of prevalent pulmonary disorders including lung cancer, asthma and cystic fibrosis. However, progress in this area has been hindered due to the lack of carriers that can efficiently deliver siRNA to lung epithelial cells, and also due to challenges in developing oral inhalation (OI) formulations for the regional administration of siRNA and their carriers to the lungs. In this work we report the ability of generation four, amine-terminated poly(amidoamine) (PAMAM) dendrimer (G4NH2)–siRNA complexes (dendriplexes) to silence the enhanced green fluorescent protein (eGFP) gene on A549 lung alveolar epithelial cells stably expressing eGFP. We also report the formulation of the dendriplexes and their aerosol characteristics in propellant-based portable OI devices. The size and gene silencing ability of the dendriplexes was seen not to be a strong function of the N/P ratio. Silencing efficiencies of up to 40% are reported. Stable dispersions of the dendriplexes encapsulated in mannitol and also in a biodegradable and water-soluble co-oligomer were prepared in hydrofluoroalkane (HFA)-based pressurized metered-dose inhalers (pMDIs). Their aerosol characteristics were very favorable, and conducive to deep lung deposition, with respirable fractions of up to 77%. Importantly, siRNA formulated as dendriplexes in pMDIs was shown to keep its integrity after the particle preparation processes, and also after long-term exposures to HFA. The relevance of this study stems from the fact that this is the first work to report the formulation of inhalable siRNA with aerosol properties suitable to deep lung deposition using pMDIs devices that are the least expensive and most widely used portable inhalers. This study is relevant because, also for the first time, it shows that siRNA–G4NH2 dendriplexes can efficiently target lung alveolar epithelial A549 cells and silence genes even after si

  15. Arginine–glycine–aspartic acid–polyethylene glycol–polyamidoamine dendrimer conjugate improves liver-cell aggregation and function in 3-D spheroid culture

    Directory of Open Access Journals (Sweden)

    Chen Z

    2016-08-01

    Full Text Available Zhanfei Chen,1,* Fen Lian,1,* Xiaoqian Wang,1 Yanling Chen,1,2 Nanhong Tang1,2 1Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, 2Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Research Center for Molecular Medicine, Fujian Medical University, Fuzhou, People’s Republic of China *These authors contributed equally to this work Abstract: The polyamidoamine (PAMAM dendrimer, a type of macromolecule material, has been used in spheroidal cell culture and drug delivery in recent years. However, PAMAM is not involved in the study of hepatic cell-spheroid culture or its biological activity, particularly in detoxification function. Here, we constructed a PAMAM-dendrimer conjugate decorated by an integrin ligand: arginine–glycine–aspartic acid (RGD peptide. Our studies demonstrate that RGD–polyethylene glycol (PEG–PAMAM conjugates can promote singly floating hepatic cells to aggregate together in a sphere-like growth with a weak reactive oxygen species. Moreover, RGD-PEG-PAMAM conjugates can activate the AKT–MAPK pathway in hepatic cells to promote cell proliferation and improve basic function and ammonia metabolism. Together, our data support the hepatocyte sphere treated by RGD-PEG-PAMAM conjugates as a potential source of hepatic cells for a biological artificial liver system. Keywords: dendrimer, arginine–glycine–aspartic acid (RGD, liver cell, spheroid culture, ammonia metabolism

  16. 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.

  17. Electrochemical One-Electron Oxidation of Low-Generation Polyamidoamine-Type Dendrimers with a 1,4-Phenylenediamine Core

    DEFF Research Database (Denmark)

    Hammerich, Ole; Hansen, Thomas; Thorvildsen, Asbjørn;

    2009-01-01

    ,N,N',N'-tetra-n-alkyl-p-phenylenediamines, including a planar arrangement of the atoms linked to the two PD nitrogen atoms. Thus, the effect of chain size on the oxidation potential appears to be caused primarily by a simple electronic effect. The calculations indicate considerable reorientation of the dendrimer side chains on oxidation, presumably...... peak heights vary approximately as predicted from the Stokes-Einstein-Sutherland equation, but the variation of the relative effective radii with the size of the dendrimer is much larger than predicted from the radii obtained by the DFT calculations, that is, the dendrimers exist in solution mainly as...

  18. Characterization of Modified Polyamidoamine Anionic Dendrimer%改性聚酰胺-胺阴离子树状聚合物的性能研究

    Institute of Scientific and Technical Information of China (English)

    彭晓春; 彭晓宏; 赵建青; 彭密军

    2011-01-01

    研究了改性聚酰胺-胺(PAMAM)阴离子树状聚合物的特性黏数([η])、热稳定性和絮凝性能.实验结果表明,该类树状聚合物的[η]随代数的增加先增大后减小,出现一个极大值.PAMAM/丙烯酸钠(SAA)、含聚氧乙烯(PEO)链端的PAMAM/SAA(PAMAM/SAA/PEO)阴离子树状聚合物的[η]极大值分别出现在第4.0代附近、第5.0 ~6.0代附近;随PEO相对分子质量的增加,PAMAM/SAA/PEO阴离子树状聚合物的[η]减小.热分析结果表明,改性PAMAM阴离子树状聚合物具有逐层热分解行为,热稳定性与分子外围端基有关,PAMAM/SAA/PEO阴离子树状聚合物具有更好的热稳定性,最大热失重速率对应的温度可达388℃.改性PAMAM阴离子树状聚合物具有一定的絮凝性能,絮凝件能随代数、PEO链长的增加而增强;改性PAMAM阴离子树状聚合物的最佳浓度为30 mg/L(不是所有的改性PAMAM阴离子树状聚合物的最佳浓度都是30 mg/L),上层清液的透光率达85%以上.%The intrinsic viscosities, thermal stabilities and flocculations of the modified polyamidoamine (PAMAM) anionic dendrimers were studied. The results showed that the intrinsic viscosities of the dendrimers increased at first and then decreased with the increase of the generation number. The maximum intrinsic viscosities of PAMAM/sodium acrylate (SAA) and PAMAM/SAA/polyoxyethylene (PAMAM/ SAA/PEO) anionic dendrimers were at about G4. 0 and between G5. 0 and G6. 0, respectively. The intrinsic viscosities of PAMAM/SAA/PEO anionic dendrimers decreased with the increase of the number-average relative molecular mass of PEO macromonomers. The thermal analysis indicated that thermal decomposition of the modified PAMAM anionic dendrimer was of multiple steps, and the thermal stability depended on the exterior terminal groups. PAMAM/SAA/PEO anionic dendrimer has better thermal stability than the others, according to its maximum mass loss rate at 388 t. The modified PAMAM anionic

  19. Evaluation of the activity of new cationic carbosilane dendrimers on trophozoites and cysts of Acanthamoeba polyphaga.

    Science.gov (United States)

    Heredero-Bermejo, Irene; Copa-Patiño, Jose Luis; Soliveri, Juan; Fuentes-Paniagua, Elena; de la Mata, Francisco Javier; Gomez, Rafael; Perez-Serrano, Jorge

    2015-02-01

    Dendrimers are repetitively branched molecules with a broad spectrum of applications, mainly for their antimicrobial properties and as nanocarriers for other molecules. Recently, our research group have synthesized and studied their activity against Acanthamoeba sp., causative agent of a severe ocular disease in humans: Acanthamoeba keratitis. New cationic carbosilane dendrimers were tested against the protozoa forms at different concentrations and for different incubation times. Trophozoite viability was determined by manual counting and cyst viability by observing excystment in microplates with fresh culture medium. Cytotoxicity was checked on HeLa cells using the microculture tetrazolium assay. Alterations were observed by optical microscopy and by flow cytometry staining with propidium iodide. Six out of the 18 dendrimers tested were non-cytotoxic and effective against the trophozoite form, having one of them (dendrimer 14 with an IC50 of 2.4 + 0.1 mg/L) a similar activity to chlorhexidine digluconate (IC50 1.7 + 0.1 mg/L). This dendrimer has a polyphenoxo core and a sulphur atom close to the six -NH3+ terminal groups. On the other hand, only two dendrimers showed some effect against cysts (dendrimers 14 and 17). However, their minimum cysticidal concentrations were cytotoxic and less effective than the control drug. The alterations on the amoeba morphology produced by the treatment with dendrimers were size reduction, increased complexity, loss of acanthopodia and cell membrane disruption. In conclusion, these results suggest that some dendrimers may be studied in animal models to test their effect and that new dendrimers with similar features should be synthesized. PMID:25358240

  20. Nano Polyamidoamine-G7 (NPAMAM-G7 Dendrimer Synthesis and Assessment the Effect of its antibacterial on Escherichia Coli, Klebsiella Oxytoca, Pseudomonas Aeruginosa , Proteus Mirabilis and Staphylococcus Aureus from aqueous solution

    Directory of Open Access Journals (Sweden)

    mitra Gholami

    2016-06-01

    Full Text Available Background: Nano scale dendrimers are macromolecules synthetic which frequently used in medical and health field. This study was aimed to examine synthesis and the antibacterial effect of NanoPolyamidoamine-G7 (NPAMAM-G7 dendrimer on Escherichia Coli, Klebsiella Oxytoca, Pseudomonas Aeruginosa , Proteus Mirabilis and Staphylococcus Aureus from aqueous solution. Material and methods: In this experimental study, initially dilution of 103 CFU/ml were prepared from each strain of bacteria. Then different concentrations of dendrimer (0.025, 0.25, 2.5 and 25 µg/ml in the laboratory temperature (23-25 °C was added to water. In order to determine the efficiency of dendrimers in removal of bacteria, samples were taken at different times (0, 10, 20, 30, 40, 50 and 60 min and were cultured on nutrient agar medium. Samples were incubated for 24 hours at 37 °C and then number of colonies were counted. Results: Antibacterial properties of dendrimers in aqueous solution by increasing the dendrimer concentration and contact time is directly related. At a concentration of 25 μg/ml at 60 minutes all bacteria except Staphylococcus Aureus, and at 30 minutes, Escherichia Coli and Klebsiella Oxytoca bacteria for 100% excluded. The concentration of 2.5 μg/ml at 60 minutes of bacteria, Escherichia Coli, Klebsiella Oxytoca and Proteus Mirabilis are 100% excluded. All concentrations of dendrimers at different times were reduced bacteria in the PAMAM- G7 dendrimer effect on gram-negative bacteria, gram-positive bacteria was better. Conclusion: The NPAMAM-G7 dendrimer with end amine groups exhibited a positive impact on the removal of standard strains, gram-positive and gram-negative bacteria. Therefore, it is possible to use these nanodendrimers as antibacterial in the future.

  1. Involvement of functional groups on the surface of carboxyl group-terminated polyamidoamine dendrimers bearing arbutin in inhibition of Na⁺/glucose cotransporter 1 (SGLT1)-mediated D-glucose uptake.

    Science.gov (United States)

    Sakuma, Shinji; Kanamitsu, Shun; Teraoka, Yumi; Masaoka, Yoshie; Kataoka, Makoto; Yamashita, Shinji; Shirasaka, Yoshiyuki; Tamai, Ikumi; Muraoka, Masahiro; Nakatsuji, Yohji; Kida, Toshiyuki; Akashi, Mitsuru

    2012-04-01

    A carboxyl group-terminated polyamidoamine dendrimer (generation: 3.0) bearing arbutin, which is a substrate of Na⁺/glucose cotransporter 1 (SGLT1), via a nonbiodegradable ω-amino triethylene glycol linker (PAMAM-ARB), inhibits SGLT1-mediated D-glucose uptake, as does phloridzin, which is a typical SGLT1 inhibitor. Here, since our previous research revealed that the activity of arbutin was dramatically improved through conjugation with the dendrimer, we examined the involvement of functional groups on the dendrimer surface in inhibition of SGLT1-mediated D-glucose uptake. PAMAM-ARB, with a 6.25% arbutin content, inhibited in vitro D-glucose uptake most strongly; the inhibitory effect decreased as the arbutin content increased. In vitro experiments using arbutin-free original dendrimers indicated that dendrimer-derived carboxyl groups actively participated in SGLT1 inhibition. However, the inhibitory effect was much less than that of PAMAM-ARB and was equal to that of glucose moiety-free PAMAM-ARB. Data supported that the glucose moiety of arbutin was essential for the high activity of PAMAM-ARB in SGLT1 inhibition. Analysis of the balance of each domain further suggested that carboxyl groups anchored PAMAM-ARB to SGLT1, and the subsequent binding of arbutin-derived glucose moieties to the target sites on SGLT1 resulted in strong inhibition of SGLT1-mediated D-glucose uptake.

  2. 树枝状聚酰胺-胺紫外光固化树脂的合成%Synthesis of UV-Curing Polyamidoamine Dendrimer Resin

    Institute of Scientific and Technical Information of China (English)

    胡加娟; 郭秀生; 于德梅; 苏敏茹; 郭容男

    2011-01-01

    采用发散法合成了以乙二胺为核的0.5 ~3.5代树枝状大分子聚酰胺-胺(PAMAM),研究了半代PAM-AM在酸性条件下的水解反应,用傅里叶变换红外光谱和核磁共振法对半代PAMAM和PAMAM水解酸进行了表征.通过丙烯酸羟乙酯与半代PAMAM水解酸的反应,合成了不需添加稀释剂,在紫外光作用下便能同化成膜的树枝状聚酰胺-胺紫外光固化树脂,得到的光固化膜表面光滑、柔软、颜色均匀、内部无气泡且表观性能较好,解决了为降低高分子材料黏度必须加入大量稀释剂的问题.傅里叶变换红外光谱证明了丙烯酸羟乙酯改性成功,测定了合成的光固化树脂溶解性、紫外光固化膜的熔点、热稳定性等性能,并对其性能变化的规律进行了探讨.测试表明合成的产物不同,其溶解性能有较大的不同,只能溶解在极性较大的水、甲醇、N,Ⅳ-二甲基甲酰胺中.随着代数的增加,紫外光固化膜的熔点逐渐降低;TG分析表明紫外光固化膜的热分解反应是一个由外层向内层分步进行的过程,初始分解均在170℃以上,固化膜具有较好的稳定性.%A series of polyamidoamine(PAMAM) dendrimer from 0. 5 generation to 3. 5 generation have been synthesized by divergent method. Half generation of PAMAM (0. 5G,1. 5G,2. 5G,3. 5G) were hydroly-sised in acidic conditions. The compositions and structures of half generation of PAMAM and its hydrolyzed products were characterized by means of FT - IR and ' H NMR. The hydrolyzed products were modified with hydroxyethyl acrylate to form a UV - curable polyamidoamine dendrimer which couled be cured under UV -light without diluent. Film surface was smooth,soft,uniform color,no air bubbles inside and showed a better apparent performance, solving the problem that a lot of thinner needed to be added in order to reduce the viscosity of polymer materials. FT - IR proved the success of modification. The properties of the modified

  3. Polyamidoamine dendrimers as sweeping agent and stationary phase for rapid and sensitive open-tubular capillary electrophoretic determination of heavy metal ions.

    Science.gov (United States)

    Ge, Ying; Guo, Yujun; Qin, Weidong

    2014-04-01

    Polyamidoamine (PAMAM) dendrimer generation 2.5 was synthesized and evaluated as sweeping agent for in-column enrichment and as stationary phase for capillary electrochromatographic separation of heavy metal ions, viz., Pb(II), Cu(II), Hg(II), Zn(II) and Co(II), in a running buffer containing 4-(2-pyridylazo)resorcinol (PAR) as a chromogenic reagent. During experiment, a plug of aqueous PAMAM generation 2.5 solution was first introduced to the capillary, followed by electrokinetic injection of the heavy metal ions under a positive voltage. In this step, PAMAM acted as a sweeping agent, stacking the metal ions on the analyte/PAMAM boundary by forming metal ion-PAMAM complexes. The second preconcentration process occurred when PAR, a stronger ligand, moving toward the injection end under the electric field, reached and re-swept the metal ion-PAMAM zone, forming metal ion-PAR complexes. During separation, the neutral PAMAM moved toward the detector with the electroosmotic flow, dynamically coating the capillary wall, forming stationary phases that affected the separation of the metal ions. Due to the function of PAMAM, the detection sensitivity and resolution of the heavy metal ions improved significantly. Under the optimum conditions, the detection limits were 0.299, 0.184, 0.774, 0.182 and 0.047 μg/L for Pb(II), Cu(II), Hg(II), Zn(II) and Co(II), respectively. The method was successfully applied to the determination of heavy metals in snow, tap and rain water samples. PMID:24607109

  4. 季铵化树状聚酰胺-胺的合成及表征%Synthesis and Characterization of Quaternized Polyamidoamine Dendrime

    Institute of Scientific and Technical Information of China (English)

    王学川; 何林燕; 强涛涛

    2011-01-01

    The 0.5~1.0 generation of polyamidoamine dendrime (PAMAM) was synthesized via Michael-additive action of alkylene diamine and methyl acrylate from ethylenediamine and methacrylate. 1.0G PAMAM was grafted with (2,3-epoxypropyl) trimethyl ammonium chloride (EPTAC), thus 1.0G PAMAM-TAC was prepared. By the method of one-factor experimental design, rome correlative factors that influenced the 1.0G PAMAM-TAC were investigated, the appropriate action conditions were optimized as follows: solvent consumption 40% (ba.ed on the total mass of reaction system), reaction temperature 55 ℃, reaction time 5 h, n (1.0GPAMAM): n (EPTAC) = 1:8. The polymer was characterized by infrared spectrum (IR), nuclear magnetic resonance spectrum (1H and 13CNMR).%以乙二胺和丙烯酸甲酯为原料,通过Michael加成反应和酰胺化反应合成了0.5代~1.0代树状聚酰胺-胺(0.5G~1.0G PAMAM).再利用缩水甘油三甲基氯化铵(EPTAC)对1.0G PAMAM进行接枝改性制备了1.0代树状聚酰胺-胺的季铵盐(1.0G PAMAM-TAC).通过单因素试验筛选出了1.0G PAMAM-TAC的最佳反应条件:溶剂用量40%(以反应体系的总质量计)、反应温度55℃、反应时间5 h、投料摩尔比n(1.0GPAMAM):n(EPTAC)为1:8.采用红外光谱和核磁共振波谱对改性前后1.0GPAMAM的结构进行了表征.

  5. 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.

  6. Wiring of Glucose Oxidizing Flavin Adenine Dinucleotide-Dependent Enzymes by Methylene Blue-Modified Third Generation Poly(amidoamine) Dendrimers Attached to Spectroscopic Graphite Electrodes

    DEFF Research Database (Denmark)

    Castaing, Victor; Álvarez-Martos, Isabel; Ferapontova, Elena

    2016-01-01

    ordered multiple redox centers, represent an advanced alternative to the existing approaches. Here we show that methylene blue (MB)-labeled G3 PAMAM dendrimers covalently attached to the high-surface area spectroscopic graphite (Gr) electrodes form stable and spatially resolved electronic wires......, characterized by the heterogeneous ET rate constant of 7.1 0.1 s1; they can be used for electronic wiring of glucose-oxidizing FAD-containing enzymes, such as hexose oxidase (HOX), and further bioelectrocatalysis of glucose oxidation, starting, at pH 7, from -100 mV vs. Ag/AgCl. Thus, dendrimer......-templated electronic wires, comprising MB molecules conjugated to the periphery of the PAMAM and anchored to the surface of cost-effective Gr electrodes represent an efficient and robust tool for protein wiring to electrodes for their perspective bioelectronic applications in biosensors and biofuel cells....

  7. 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

  8. Study of streptavidin coated onto PAMAM dendrimer modified magnetite nanoparticles

    International Nuclear Information System (INIS)

    Polyamidoamine dendrimer was synthesized on the surface of amino silane modified magnetite nanoparticles. After coating of streptavidin to these dendrimer-modified magnetite nanoparticles, an up to 3.4 times higher amount of streptavidin (SA) was measured compared to magnetite nanoparticles modified with only amino silane. The biotin-binding capacity of SA thus increased after dendrimer modification

  9. 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.

  10. Dendrimer-Capped Nanoparticles Prepared by Picosecond Laser Ablation in Liquid Environment

    Directory of Open Access Journals (Sweden)

    Paolo Marsili

    2009-09-01

    Full Text Available Fifth generation ethylendiamine-core poly(amidoamine (PAMAM G5 is presented as an efficient capping agent for the preparation of metal and semiconductor nanoparticles by ps laser ablation in water. In particular, we describe results obtained with the fundamental, second and third harmonic of a ps Nd:YAG laser and the influence of laser wavelength and pulse energy on gold particle production and subsequent photofragmentation. In this framework, the role of the dendrimer and, in particular, its interactions with gold clusters and cations are accounted.

  11. 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…

  12. IMMUNOSTIMULATORY PROPERTIES OF DENDRIMERS MULTIVALENTLY PRESENTING MURAMYLDIPEPTIDE

    DEFF Research Database (Denmark)

    as PGN. Interestingly, whereas PGN induced a considerable IL-10-production, no IL-10 was induced by the MDP-conjugated dendrimers. By flow cytometry, enhanced cell death was detected in response to unmodified PPI-dendrimers, whereas none of the MDP-conjugated dendrimers showed any detectable...... of PAMP minimal motifs on the surface of monodisperse hyperbranched globular synthetic polymers, dendrimers. Two sizes of polypropylene-imine (PPI) and polyamido-amine (PAMAM) dendrimers were conjugated with muramyldipeptide (MDP), the minimal essential motif of peptidoglycan (PGN), to yield...... constructs presenting a theoretical number of 16 and 32 MDP molecules, respectively. These conjugates were tested for cytotoxicity, and for their ability to induce cytokines and upregulate MHC and costimulatory molecules in porcine peripheral blood mononuclear cells. Results: Both MDP-PPI and MDP...

  13. Preparation and characterization of conjugated polyamidoamine-MPEG-methotrexate for potential drug delivery system

    Science.gov (United States)

    Mohd Sabri, Siti Noorzidah bt; Abu, Norhidayah; Mastor, Azreena; Hisham, Siti Farhana; Noorsal, Kartini

    2012-07-01

    Star polymers have unique characteristics due to their well-defined size and tailor ability which makes these polymers attractive candidates as carriers in drug delivery system applications. This work focuses on attaching a drug to the star polymer (polyamidoamine). The conjugation of polyamidoamine (PAMAM, generation 4) with methotrexate (MTX) (model drug) was studied in which monomethyl polyethylene glycol (MPEG) was used as a linker to reduce the toxicity of dendrimer. Conjugation starts with attaching the drug to the linker and followed by further conjugation with the polyamidoamine (PAMAM) dendrimer. The conjugation of PAMAM-PEG-MTX was confirmed through UV-Vis, FTIR, 1H NMR and DSC. The loading capacities and release profile of this conjugate were determined using 1H NMR and UV spectrometer.

  14. Design of Dendrimer Modified Carbon Nanotubes for Gene Delivery

    Institute of Scientific and Technical Information of China (English)

    PAN Bi-feng; BAO Chen-chen; GAO Feng; HE Rong; SHU Meng-jun; MA Yong-jie; CUI Da-xiang; XU Ping; CHEN Hao; LIU Feng-tao; LI Qing; HUANG Tuo; YOU Xiao-gang; SHAO Jun

    2007-01-01

    Objective: To investigate the efficiency of polyamidoamine dendrimer grafted carbon nanotube (dendrimer-CNT) mediated entrance of anti-survivin oligonucleotide into MCF-7 cells, and its effects on the growth of MCF-7 cells. Methods: Antisense survivin oligonucleotide was anchored onto polyamidoamine dendrimer grafted carbon nanotubes to form dendrimer-CNT-asODN complex and the complex was characterized by Zeta potential, AFM, TEM, and 1% agarose gel electrophoresis analysis. Dendrimer-CNT-asODN complexes were added into the medium and incubated with MCF-7 cells. MTT method was used to detect the effects of asODN and dendrimer-CNT-asODN on the growth of MCF-7 cells. TEM was used to observe the distribution of dendrimer-CNT-asODN complex within MCF-7 cells. Results: Successful synthesis of dendrimer-CNT-asODN complexes was proved by TEM, AFM and agarose gel electrophoresis. TEM showed that the complexes were located in the cytoplasm, endosome, and lysosome within MCF-7 cells. When dendrimer-CNT-asODN (1.0 μmol/L) and asODN (1.0 μmol/L) were used for 120 h incubation, the inhibitory rates of MCF-7 cells were (28.22±3.5)% for dendrimer-CNT-asODN complex group, (9.23±0.56)% for only asODN group, and (3.44±0.25)% for dendrimer-CNT group. Dendrimer-CNT-asODN complex at 3.0 μmol/L inhibited MCF-7 cells by (30.30±10.62)%, and the inhibitory effects were in a time- and concentration- dependent manner. Conclusion: Dendrimer-CNT nanoparticles may serve as a gene delivery vector with high efficiency, which can bring foreign gene into cancer cells, inhibiting cancer cell proliferation and markedly enhancing the cancer therapy effects.

  15. Poly(amidoamine) (PAMAM): An emerging material for electrochemical bio(sensing) applications.

    Science.gov (United States)

    Bahadır, Elif Burcu; Sezgintürk, Mustafa Kemal

    2016-02-01

    Poly(amidoamine) (PAMAM) dendrimers have received attention due to their large surface areas with high concentration of functional end groups to bind biological material. They are monodisperse and hyper-branched polymers which include active functional groups outside its surface. These functional groups have been used for immobilizing the biorecognition molecules. They act as bioconjugating reagents and they have various applications in the fields of chemical and biochemical biosensors. Electrochemical techniques (amperometric, impedimetric, potentiometric, electrochemiluminescence) are useful for the determination of target molecules, with high sensitivity and selectivity. Dendrimer-modified enzyme biosensors, DNA biosensors, immunosensors and chemical sensors have been fabricated by using PAMAM dendrimer. This review provides a brief description of PAMAM dendrimers and its applications in biosensors and sensors. These sensors' limit of detection values are also compared in detail. Also this is the first review that assesses PAMAM dendrimers from the point of its usability in biosensor and sensor technologies.

  16. In vitro anti-Acanthamoeba synergistic effect of chlorhexidine and cationic carbosilane dendrimers against both trophozoite and cyst forms.

    Science.gov (United States)

    Heredero-Bermejo, I; Sánchez-Nieves, J; Soliveri, J; Gómez, R; de la Mata, F J; Copa-Patiño, J L; Pérez-Serrano, J

    2016-07-25

    Acanthamoeba sp. are the causative agents of severe illnesses in humans such as Acanthamoeba keratitis (AK) and granulomatous amoebic encephalitis (GAE). Medical therapy is not yet well established. Treatments of AK last for several months and generate toxicity, resistances appear due to the cysts stage and recurrences can occur. In this study has been demonstrated that the combination of chlorhexidine digluconate (CLX) and carbosilane dendrimers containing ammonium or guanidine moieties has in vitro synergistic effect against Acanthamoeba polyphaga. This synergy provokes an important reduction in the minimal trophozoite amoebicidal concentration (MTAC) of CLX, which means a reduction of their toxic effects on human cells. Moreover, some CLX/dendrimer combinations show important activity against the cyst resistance stage. PMID:27173821

  17. 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...

  18. Characterization of crystalline dendrimer-stabilized gold nanoparticles

    Science.gov (United States)

    Shi, Xiangyang; Ganser, T. Rose; Sun, Kai; Balogh, Lajos P.; Baker, James R., Jr.

    2006-02-01

    Monodispersed, highly crystalline dendrimer-stabilized gold nanoparticles (Au DSNPs) were synthesized via hydrazine reduction chemistry and stabilized using primary amine-terminated poly(amidoamine) (PAMAM) dendrimers of different generations (generations 2-6) with the same molar ratios of dendrimer terminal nitrogen ligands/gold atoms. The sizes of the synthesized Au DSNPs decrease with the increase of the number of dendrimer generations. These Au DSNPs are fluorescent and display strong blue emission intensity at 458 nm. Polyacrylamide gel electrophoresis (PAGE) analysis indicates that all Au DSNPs are stable and both metal NPs and dendrimer stabilizers do not separate from each other during the electrophoresis process. The synthesized inorganic/organic hybrid Au DSNPs provide new nanoplatforms that will be further modified with various biological ligands for the application of biosensing and targeted cancer therapeutics.

  19. Generation-dependent effect of PAMAM dendrimers on human insulin fibrillation and thermal stability.

    Science.gov (United States)

    Nowacka, Olga; Milowska, Katarzyna; Belica-Pacha, Sylwia; Palecz, Bartlomiej; Šipošová, Katarina; Gazova, Zuzana; Bryszewska, Maria

    2016-01-01

    We have studied the effect of polyamidoamine (PAMAM) dendrimers of various generations on the thermal stability and fibrillation of human insulin. Thermostability of human insulin used differential scanning calorimetry (DSC), which showed two phase-transitions for insulin at 60 and 82°C. After adding dendrimers at 0.6 μmol/l, the first peaks disappeared and the second peaks were higher. We posited that, in the presence of dendrimers, the dimers in the solution were transformed into hexamers. The effect of dendrimers on insulin fibrillation was monitored by measuring ThT fluorescence, and visualization of insulin fibrils by transmission electron microscopy (TEM) and atomic force microscopy (AFM). The effect of PAMAM dendrimers on insulin fibrillation was strongly dependent on the dendrimers generation and dendrimer:protein ratio. PMID:26598047

  20. 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.

  1. Polyester Dendrimers

    Directory of Open Access Journals (Sweden)

    Jean–d’Amour K. Twibanire

    2012-03-01

    Full Text Available Polyester dendrimers have been comprehensively reviewed starting from their first synthesis in the early 1990s by Hawker and Fréchet. Polyester dendrimers have attracted and continue to attract extensive interest because they are comparatively easy to make and because, whenever they have been tested, they have been found to be non-toxic. A number of different strategies for their synthesis have been examined and the methods employed for formation of the ester bond during dendrimer assembly have been summarized. The newest approaches, including the use of bifunctional orthogonally reacting dendrons and accelerated synthesis have been surveyed.

  2. Fluorescence study on the interactions of PAMAM dendrimers and their derivatives with bovine serum albumin

    Institute of Scientific and Technical Information of China (English)

    WANG Yanming; SONG Yu; KONG Deling; YU Yaoting

    2005-01-01

    The interactions of amino-terminated, and ethylenediamine core poly(amidoamine) (PAMAM) dendrimers and their derivatives with bovine serum albumin (BSA) were investigated by fluorescence spectroscopy. Experimental results showed that the fluorescence intensity of BSA decreased after the addition of different modified dendrimers, and the extent of the fluorescence quenching caused by various modified dendrimers strongly depends upon the different functional groups on their surfaces. We also investigated the influence of pH and ionic strength on the interaction between various modified dendrimers and BSA. Circular dichroism (CD) spectroscopic measurements showed that the content of α-helix structure of BSA decreased after the addition of different modified dendrimers, which indicated that dendrimers induced changes in the secondary structure of BSA.

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

    International Nuclear Information System (INIS)

    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

  4. 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)

  5. 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

  6. Dendrimer-Mediated Adhesion between Vapor-Deposited Au and Glass or Si Wafers.

    Science.gov (United States)

    Baker, L A; Zamborini, F P; Sun, L; Crooks, R M

    1999-10-01

    Here, we report the use of amine-terminated poly(amidoamine) (PAMAM) dendrimers as adhesion promoters between vapor-deposited Au films and Si-based substrates. This method is relatively simple, requiring only substrate cleaning, dipping, and rinsing. Proof of concept is illustrated by coating glass slides and single-crystal Si wafers with monolayers of PAMAM dendrimers and then evaporating adherent, 150-nm-thick Au films atop the dendritic adhesion promoter. Scanning tunneling microscopy and cyclic voltammetry have been used to assess the surface roughness and electrochemical stability of the Au films. The effectiveness of the dendrimer adhesion layer is demonstrated using standard adhesive-tape peel tests.

  7. Advance in polyamidoamine dendrimers as gene delivery agents

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    @@ Gene therapy recently has become an important area of research as a new therapeutic method. In vivo and in vitro gene therapies require efficient delivery of genetic material into a cell and preferably high levels of expression of transferred gene. Traditionally, gene delivery systems are classified as viral vector-mediated systems and nonviral vector-mediated systems. Viral vectors, which have been demonstrated as systems with high transfection efficiency, however, are limited due to adverse effects such as immunogenicity, toxicity, limited DNA carrying capacity and mutagenesis caused by cell-infected viruses[1].

  8. Dendrimers for siRNA Delivery.

    Science.gov (United States)

    Biswas, Swati; Torchilin, Vladimir P

    2013-01-01

    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. PMID:24275946

  9. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Nowacka, Olga; Milowska, Katarzyna, E-mail: milowska@biol.uni.lodz.pl; Bryszewska, Maria

    2015-06-15

    We have looked at the interactions between polyamidoamine (PAMAM) dendrimers with different terminal groups (−COOH, −NH{sub 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.

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

    International Nuclear Information System (INIS)

    We have looked at the interactions between polyamidoamine (PAMAM) dendrimers with different terminal groups (−COOH, −NH2, −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

  12. Multiscale Modeling for Host-Guest Chemistry of Dendrimers in Solution

    Directory of Open Access Journals (Sweden)

    Seung Ha Kim

    2012-02-01

    Full Text Available Dendrimers have been widely used as nanostructured carriers for guest species in a variety of applications in medicine, catalysis, and environmental remediation. Theory and simulation methods are an important complement to experimental approaches that are designed to develop a fundamental understanding about how dendrimers interact with guest molecules. This review focuses on computational studies aimed at providing a better understanding of the relevant physicochemical parameters at play in the binding and release mechanisms between polyamidoamine (PAMAM dendrimers and guest species. We highlight recent contributions that model supramolecular dendrimer-guest complexes over the temporal and spatial scales spanned by simulation methods ranging from all-atom molecular dynamics to statistical field theory. The role of solvent effects on dendrimer-guest interactions and the importance of relating model parameters across multiple scales is discussed.

  13. Dendrimers for siRNA Delivery

    OpenAIRE

    Swati Biswas; Torchilin, Vladimir P.

    2013-01-01

    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 cation...

  14. Dendrimer Templates for the Formation of Silver Nanoparticles

    Institute of Scientific and Technical Information of China (English)

    LI Guo-ping; LUO Yun-jun; XU Hou-cai; TAN Hui-min

    2006-01-01

    In order to control the size and shape of Ag nanoparticles obtained by using poly(amidoamine) (PAMAM) dendrimer as template, the complexation between Ag+ ions and dendrimer studied extensively by UVVis spectroscopy and FTIR. After the Ag+/PAMAM demdrimer being reduced by direct chemical reduction,Ag (0) nanoparticles was formed, whose structure and characterization were studied by UV-Vis spectroscopy,transmission electron microscopy (TEM) and electron diffraction (ED) respectively. The results reveal that Ag nanoparticles is a kind of face center cubic crystal and its average size is 4.5 nm. The solubility and stability of the solution containing Ag nanoparticles also indicate that dendrimer is a good kind of template, as well as a protective agent.

  15. On the nanotoxicity of PAMAM dendrimers: Superfect® stimulates the EGFR-ERK1/2 signal transduction pathway via an oxidative stress-dependent mechanism in HEK 293 cells.

    Science.gov (United States)

    Akhtar, Saghir; Chandrasekhar, Bindu; Attur, Sreeja; Yousif, Mariam H M; Benter, Ibrahim F

    2013-05-01

    Polyamidoamine (PAMAM) dendrimers are cationic branch-like macromolecules that may serve as drug delivery systems for gene-based therapies such as RNA interference. For their safe use in the clinic, they should ideally only enhance drug delivery to target tissues and exhibit no adverse effects. However, little is known about their toxicological profiles in terms of their interactions with cellular signal transduction pathways such as the epidermal growth factor receptor (EGFR). The EGFR is an important signaling cascade that regulates cell growth, differentiation, migration, survival and apoptosis. Here, we investigated the impact of naked, unmodified Superfect (SF), a commercially available generation 6 PAMAM dendrimer, on the epidermal growth factor receptor (EGFR) tyrosine kinase-extracellular-regulated kinase 1/2 (ERK1/2) signaling pathway in human embryonic kidney (HEK 293) cells. At concentrations routinely used for transfection, SF exhibited time and dose-dependent stimulation of EGFR and ERK1/2 phosphorylation whereas AG1478, a selective EGFR tyrosine kinase antagonist, inhibited EGFR-ERK1/2 signaling. SF-induced phosphorylation of EGFR for 1h was partly reversible upon removal of the dendrimer and examination of cells 24 later. Co-treatment of SF with epidermal growth factor (EGF) ligand resulted in greater EGFR stimulation than either agent alone implying that the stimulatory effects of SF and the ligand are synergistic. Dendrimer-induced stimulation of EGFR-ERK1/2 signaling could be attenuated by the antioxidants apocynin, catalase and tempol implying that an oxidative stress dependent mechanism was involved. These results show for the first time that PAMAM dendrimers, aside from their ability to improve drug delivery, can modulate the important EGFR-ERK1/2 cellular signal transduction pathway - a novel finding that may have a bearing on their safe application as drug delivery systems.

  16. 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.

  17. Potential drug delivery agent— polyamidoamine

    Institute of Scientific and Technical Information of China (English)

    YE Ling; GU Wei; ZHOU Yu-lan; LIU Yong-li; YANG Hua

    2001-01-01

    @@ INTRODUCTION Since their introduction in mid-1980s, polyamidoamide (P AMAM) dendrimershave attracted considerable attention because of their unique structures and properties. According to preliminary studies in animals, PAMAM dendrimers are non-immunogenic, very low in vivo toxicity and can be excreted by urine and feces.

  18. Synthesis and characterization of supramolecule self-assembly polyami-doamine (PAMAM G1-G1 NH2, CO2H end group Megamer

    Directory of Open Access Journals (Sweden)

    Omid Louie

    2014-10-01

    Full Text Available Supramolecule self-assembly polyamidoamine (PAMAM dendrimer refers to the chemical sys-tems made up of a discrete number of assembled molecular subunits or components. These strat-egies involve the covalent assembly of hierarchical components reactive monomers, branch cells or dendrons around atomic or molecular cores according to divergent/convergent dendritic branching principles, systematic filling of space around a core with shells (layers of branch cells. The polydispersity index (PDI for the supramolecule megamer are pretty closed to one, are in agreement with the Poisson probability distribution. Polyamidoamine (PAMAM den-drimer G1-G1 that it was PAMAM Megamer NH2, COOH end groupsynthesized and character-ized by FT-IR, 1H NMR, 13C NMRspectra and GelPermeation Chromatography (GPC.

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

    Energy Technology Data Exchange (ETDEWEB)

    Li Zhiming; Huang Peng; He Rong; Bao Chenchen; Cui Daxiang [National Key Laboratory of Nano/Micro Fabrication Technology, Key Laboratory for Thin Film and Microfabrication of Ministry of Education, Institute of Micro-Nano Science and Technology, Shanghai Jiao Tong University, Shanghai 200240 (China); Zhang Xiaomin; Ren Qiushi [Institute for Laser Medicine and Biophotonics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240 (China)], E-mail: qsren@sjtu.edu.cn, E-mail: dxcui@sjtu.edu.cn

    2009-09-01

    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.

  20. 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.

  1. Effect of Terminal Groups of Dendrimers in the Complexation with Antisense Oligonucleotides and Cell Uptake.

    Science.gov (United States)

    Márquez-Miranda, Valeria; Peñaloza, Juan Pablo; Araya-Durán, Ingrid; Reyes, Rodrigo; Vidaurre, Soledad; Romero, Valentina; Fuentes, Juan; Céric, Francisco; Velásquez, Luis; González-Nilo, Fernando D; Otero, Carolina

    2016-12-01

    Poly(amidoamine) dendrimers are the most recognized class of dendrimer. Amino-terminated (PAMAM-NH2) and hydroxyl-terminated (PAMAM-OH) dendrimers of generation 4 are widely used, since they are commercially available. Both have different properties, mainly based on their different overall charges at physiological pH. Currently, an important function of dendrimers as carriers of short single-stranded DNA has been applied. These molecules, known as antisense oligonucleotides (asODNs), are able to inhibit the expression of a target mRNA. Whereas PAMAM-NH2 dendrimers have shown to be able to transfect plasmid DNA, PAMAM-OH dendrimers have not shown the same successful results. However, little is known about their interaction with shorter and more flexible molecules such as asODNs. Due to several initiatives, the use of these neutral dendrimers as a scaffold to introduce other functional groups has been proposed. Because of its low cytotoxicity, it is relevant to understand the molecular phenomena involving these types of dendrimers. In this work, we studied the behavior of an antisense oligonucleotide in presence of both types of dendrimers using molecular dynamics simulations, in order to elucidate if they are able to form stable complexes. In this manner, we demonstrated at atomic level that PAMAM-NH2, unlike PAMAM-OH, could form a well-compacted complex with asODN, albeit PAMAM-OH can also establish stable interactions with the oligonucleotide. The biological activity of asODN in complex with PAMAM-NH2 dendrimer was also shown. Finally, we revealed that in contact with PAMAM-OH, asODN remains outside the cells as TIRF microscopy results showed, due to its poor interaction with this dendrimer and cell membranes.

  2. Effect of Terminal Groups of Dendrimers in the Complexation with Antisense Oligonucleotides and Cell Uptake.

    Science.gov (United States)

    Márquez-Miranda, Valeria; Peñaloza, Juan Pablo; Araya-Durán, Ingrid; Reyes, Rodrigo; Vidaurre, Soledad; Romero, Valentina; Fuentes, Juan; Céric, Francisco; Velásquez, Luis; González-Nilo, Fernando D; Otero, Carolina

    2016-12-01

    Poly(amidoamine) dendrimers are the most recognized class of dendrimer. Amino-terminated (PAMAM-NH2) and hydroxyl-terminated (PAMAM-OH) dendrimers of generation 4 are widely used, since they are commercially available. Both have different properties, mainly based on their different overall charges at physiological pH. Currently, an important function of dendrimers as carriers of short single-stranded DNA has been applied. These molecules, known as antisense oligonucleotides (asODNs), are able to inhibit the expression of a target mRNA. Whereas PAMAM-NH2 dendrimers have shown to be able to transfect plasmid DNA, PAMAM-OH dendrimers have not shown the same successful results. However, little is known about their interaction with shorter and more flexible molecules such as asODNs. Due to several initiatives, the use of these neutral dendrimers as a scaffold to introduce other functional groups has been proposed. Because of its low cytotoxicity, it is relevant to understand the molecular phenomena involving these types of dendrimers. In this work, we studied the behavior of an antisense oligonucleotide in presence of both types of dendrimers using molecular dynamics simulations, in order to elucidate if they are able to form stable complexes. In this manner, we demonstrated at atomic level that PAMAM-NH2, unlike PAMAM-OH, could form a well-compacted complex with asODN, albeit PAMAM-OH can also establish stable interactions with the oligonucleotide. The biological activity of asODN in complex with PAMAM-NH2 dendrimer was also shown. Finally, we revealed that in contact with PAMAM-OH, asODN remains outside the cells as TIRF microscopy results showed, due to its poor interaction with this dendrimer and cell membranes. PMID:26847692

  3. Effect of Terminal Groups of Dendrimers in the Complexation with Antisense Oligonucleotides and Cell Uptake

    Science.gov (United States)

    Márquez-Miranda, Valeria; Peñaloza, Juan Pablo; Araya-Durán, Ingrid; Reyes, Rodrigo; Vidaurre, Soledad; Romero, Valentina; Fuentes, Juan; Céric, Francisco; Velásquez, Luis; González-Nilo, Fernando D.; Otero, Carolina

    2016-02-01

    Poly(amidoamine) dendrimers are the most recognized class of dendrimer. Amino-terminated (PAMAM-NH2) and hydroxyl-terminated (PAMAM-OH) dendrimers of generation 4 are widely used, since they are commercially available. Both have different properties, mainly based on their different overall charges at physiological pH. Currently, an important function of dendrimers as carriers of short single-stranded DNA has been applied. These molecules, known as antisense oligonucleotides (asODNs), are able to inhibit the expression of a target mRNA. Whereas PAMAM-NH2 dendrimers have shown to be able to transfect plasmid DNA, PAMAM-OH dendrimers have not shown the same successful results. However, little is known about their interaction with shorter and more flexible molecules such as asODNs. Due to several initiatives, the use of these neutral dendrimers as a scaffold to introduce other functional groups has been proposed. Because of its low cytotoxicity, it is relevant to understand the molecular phenomena involving these types of dendrimers. In this work, we studied the behavior of an antisense oligonucleotide in presence of both types of dendrimers using molecular dynamics simulations, in order to elucidate if they are able to form stable complexes. In this manner, we demonstrated at atomic level that PAMAM-NH2, unlike PAMAM-OH, could form a well-compacted complex with asODN, albeit PAMAM-OH can also establish stable interactions with the oligonucleotide. The biological activity of asODN in complex with PAMAM-NH2 dendrimer was also shown. Finally, we revealed that in contact with PAMAM-OH, asODN remains outside the cells as TIRF microscopy results showed, due to its poor interaction with this dendrimer and cell membranes.

  4. Interaction of nucleic acids with carbon nanotubes and dendrimers

    Indian Academy of Sciences (India)

    Bidisha Nandy; Mogurampelly Santosh; Prabal K Maiti

    2012-07-01

    Nucleic acid interaction with nanoscale objects like carbon nanotubes (CNTs) and dendrimers is of fundamental interest because of their potential application in CNT separation, gene therapy and antisense therapy. Combining nucleic acids with CNTs and dendrimers also opens the door towards controllable self-assembly to generate various supra-molecular and nano-structures with desired morphologies. The interaction between these nanoscale objects also serve as a model system for studying DNA compaction, which is a fundamental process in chromatin organization. By using fully atomistic simulations, here we report various aspects of the interactions and binding modes of DNA and small interfering RNA (siRNA) with CNTs, graphene and dendrimers. Our results give a microscopic picture and mechanism of the adsorption of single- and double-strand DNA (ssDNA and dsDNA) on CNT and graphene. The nucleic acid–CNT interaction is dominated by the dispersive van der Waals (vdW) interaction. In contrast, the complexation of DNA (both ssDNA and dsDNA) and siRNA with various generations of poly-amido-amine (PAMAM) dendrimers is governed by electrostatic interactions. Our results reveal that both the DNA and siRNA form stable complex with the PAMAM dendrimer at a physiological pH when the dendrimer is positively charged due to the protonation of the primary amines. The size and binding energy of the complex increase with increase in dendrimer generation. We also give a summary of the current status in these fields and discuss future prospects.

  5. In vivo toxicity of poly(propyleneimine) dendrimers.

    Science.gov (United States)

    Ziemba, Barbara; Janaszewska, Anna; Ciepluch, Karol; Krotewicz, Maria; Fogel, Wiesława A; Appelhans, Dietmar; Voit, Brigitte; Bryszewska, Maria; Klajnert, Barbara

    2011-11-01

    Dendrimers are highly branched macromolecules with the potential to be used for biomedical applications. Several dendrimers are toxic owing to their positively charged surfaces. However, this toxicity can be reduced by coating these peripheral cationic groups with carbohydrate residues. In this study, the toxicity of three types of 4th generation poly (propyleneimine) dendrimers were investigated in vivo; uncoated (PPI-g4) dendrimers, and dendrimers in which 25% or 100% of surface amino groups were coated with maltotriose (PPI-g4-25%m or PPI-g4-100%m), were administered to Wistar rats. Body weight, food and water consumption, and urine excretion were monitored daily. Blood was collected to investigate biochemical and hematological parameters, and the general condition and behavior of the animals were analyzed. Unmodified PPI dendrimers caused changes in the behavior of rats, a decrease in food and water consumption, and lower body weight gain. In the case of PPI-g4 and PPI-g4-25%m dendrimers, disturbances in urine and hematological and biochemical profiles returned to normal during the recovery period. PPI-g4-100%m was harmless to rats. The PPI dendrimers demonstrated dose- and sugar-modification-degree dependent toxicity. A higher dose of uncoated PPI dendrimers caused toxicity, but surface modification almost completely abolished this toxic effect.

  6. Dendrimer-surfactant interactions.

    Science.gov (United States)

    Cheng, Yiyun; Zhao, Libo; Li, Tianfu

    2014-04-28

    In this article, we reviewed the interactions between dendrimers and surfactants with particular focus on the interaction mechanisms and physicochemical properties of the yielding dendrimer-surfactant aggregates. In order to provide insight into the behavior of dendrimers in biological systems, the interactions of dendrimers with bio-surfactants such as phospholipids in bulk solutions, in solid-supported bilayers and at the interface of phases or solid-states were discussed. Applications of the dendrimer-surfactant aggregates as templates to guide the synthesis of nanoparticles and in drug or gene delivery were also mentioned.

  7. Removal of uranium and thorium from aqueous solution by ultrafiltration (UF) and PAMAM dendrimer assisted ultrafiltration (DAUF)

    International Nuclear Information System (INIS)

    Studies on removal of U(VI) and Th(IV) from aqueous solution have been carried out by ultrafiltration (UF) and dendrimer assisted ultrafiltration (DAUF) using regenerated cellulose acetate membrane and PAMAM [poly(amido)amine] dendrimer chelating agent. In UF, the U(VI) and Th(IV) are removed from aqueous solution by adsorption/mass deposition on the membrane at pH > 4. In DAUF, the water soluble PAMAM dendrimer chelating agent effectively concentrates these metal ions in retentate thereby preventing the mass deposition on membrane. At acidic pH (≤3), the binding of metal ions with PAMAM dendrimer is very weak and hence PAMAM can be regenerated and reused. Electronic supplementary material. The online version of this article (doi:10.1007/s10967-014-3462-x) contains supplementary material, which is available to authorized users. (author)

  8. 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.

  9. Toxicity of PAMAM dendrimers to Chlamydomonas reinhardtii

    International Nuclear Information System (INIS)

    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 O2 evolution, pigments content and chlorophyll a fluorescence transient. According to the median inhibitory concentration (IC50) 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. O2 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 QA and QB were all increased inducing activation of the photosynthetic electron transport chain. These changes resulted in stimulation of full photosynthetic performance.

  10. 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.

  11. HER2 specific delivery of methotrexate by dendrimer conjugated anti-HER2 mAb

    Science.gov (United States)

    Shukla, Rameshwer; Thomas, Thommey P.; Desai, Ankur M.; Kotlyar, Alina; Park, Steve J.; Baker, James R., Jr.

    2008-07-01

    Herceptin, a humanized monoclonal antibody that binds to human growth factor receptor-2 (HER2), was covalently attached to a fifth-generation (G5) polyamidoamine dendrimer containing the cytotoxic drug methotrexate. The specific binding and internalization of this conjugate labeled with FITC was clearly demonstrated in cell lines overexpressing HER2 by flow cytometry as well as confocal microscopic analysis. In addition, binding and uptake of antibody conjugated dendrimers was completely blocked by excess non-conjugated herceptin. The dendrimer conjugate was also shown to inhibit the dihydrofolate reductase with similar activity to methotrexate. Co-localization experiments with lysotracker red indicate that antibody conjugate, although internalized efficiently into cells, has an unusually long residence time in the lysosome. Somewhat lower cytotoxicity of the conjugate in comparison to free methotrexate was attributed to the slow release of methotrexate from the conjugate and its long retention in the lysosomal pocket.

  12. HER2 specific delivery of methotrexate by dendrimer conjugated anti-HER2 mAb

    Energy Technology Data Exchange (ETDEWEB)

    Shukla, Rameshwer; Thomas, Thommey P; Desai, Ankur M; Kotlyar, Alina; Park, Steve J; Baker, James R Jr [Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, 9220 MSRB III, Box 0648, Ann Arbor, MI 48109 (United States)], E-mail: rameshwe@umich.edu, E-mail: jbakerjr@med.umich.edu

    2008-07-23

    Herceptin, a humanized monoclonal antibody that binds to human growth factor receptor-2 (HER2), was covalently attached to a fifth-generation (G5) polyamidoamine dendrimer containing the cytotoxic drug methotrexate. The specific binding and internalization of this conjugate labeled with FITC was clearly demonstrated in cell lines overexpressing HER2 by flow cytometry as well as confocal microscopic analysis. In addition, binding and uptake of antibody conjugated dendrimers was completely blocked by excess non-conjugated herceptin. The dendrimer conjugate was also shown to inhibit the dihydrofolate reductase with similar activity to methotrexate. Co-localization experiments with lysotracker red indicate that antibody conjugate, although internalized efficiently into cells, has an unusually long residence time in the lysosome. Somewhat lower cytotoxicity of the conjugate in comparison to free methotrexate was attributed to the slow release of methotrexate from the conjugate and its long retention in the lysosomal pocket.

  13. HER2 specific delivery of methotrexate by dendrimer conjugated anti-HER2 mAb

    International Nuclear Information System (INIS)

    Herceptin, a humanized monoclonal antibody that binds to human growth factor receptor-2 (HER2), was covalently attached to a fifth-generation (G5) polyamidoamine dendrimer containing the cytotoxic drug methotrexate. The specific binding and internalization of this conjugate labeled with FITC was clearly demonstrated in cell lines overexpressing HER2 by flow cytometry as well as confocal microscopic analysis. In addition, binding and uptake of antibody conjugated dendrimers was completely blocked by excess non-conjugated herceptin. The dendrimer conjugate was also shown to inhibit the dihydrofolate reductase with similar activity to methotrexate. Co-localization experiments with lysotracker red indicate that antibody conjugate, although internalized efficiently into cells, has an unusually long residence time in the lysosome. Somewhat lower cytotoxicity of the conjugate in comparison to free methotrexate was attributed to the slow release of methotrexate from the conjugate and its long retention in the lysosomal pocket

  14. Properties of mixed alkanethiol-dendrimer layers and their applications in biosensing.

    Science.gov (United States)

    Svobodová, L; Snejdárková, M; Tóth, K; Gyurcsanyi, R E; Hianik, T

    2004-06-01

    We studied the properties of mixed alkanethiol-dendrimer layers on a gold support and their application in biosensing. We showed that properties of glucose sensor can be modified using a different ratio of 1-hexadecanethiol (HDT) and poly(amidoamine) dendrimer of first generation (G1). The cyclic voltammetry in the presence of the redox couple, Fe(CN)(6)(3-)/Fe(CN)(6)(4-), was used for estimating how effectively the layer blocks the redox probe's access to the electrode surface. A scanning electrochemical microscope (SECM) was used to image the resulting distribution of the organic compounds. We found that with increasing content of dendrimers, the integrity of the layers was improved. PMID:15110289

  15. 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

  16. 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

  17. Multiscale Modeling of Dendrimers and Their Interactions with Bilayers and Polyelectrolytes

    Directory of Open Access Journals (Sweden)

    Ronald G. Larson

    2009-01-01

    Full Text Available Recent advances in molecular dynamics simulation methodologies and computational power have allowed accurate predictions of dendrimer size, shape, and interactions with bilayers and polyelectrolytes with modest computational effort. Atomistic and coarse-grained (CG models show strong interactions of cationic dendrimers with lipid bilayers. The CG simulations with explicit lipid and water capture bilayer penetration and pore formation, showing that pore formation is enhanced at high dendrimer concentration, but suppressed at low temperature and high salt concentration, in agreement with experiments. Cationic linear polymers have also been simulated, but do not perforate membranes, evidently because by deforming into a pancake, the charges on a linear polymer achieve intimate contact with a single bilayer leaflet. The relatively rigid dendrimers, on the other hand, penetrate the bilayer, because only by interacting with both leaflets can they achieve a similar degree of contact between charged groups. Also, a “dendrimer-filled vesicle” structure for the dendrimer-membrane interaction is predicted by mesoscale thermodynamic simulations, in agreement with a picture derived from experimental observations. In simulations of complexes of dendrimer and polyelectrolyte, anionic linear chains wrap around the cationic dendrimer and penetrate inside it. Overall, these new results indicate that simulations can now provide predictions in excellent agreement with experimental observations, and provide atomic-scale insights into dendrimer structure and dynamics.

  18. Hydroxyl PAMAM dendrimer-based gene vectors for transgene delivery to human retinal pigment epithelial cells

    Science.gov (United States)

    Mastorakos, Panagiotis; Kambhampati, Siva P.; Mishra, Manoj K.; Wu, Tony; Song, Eric; Hanes, Justin; Kannan, Rangaramanujam M.

    2015-02-01

    Ocular gene therapy holds promise for the treatment of numerous blinding disorders. Despite the significant progress in the field of viral and non-viral gene delivery to the eye, significant obstacles remain in the way of achieving high-level transgene expression without adverse effects. The retinal pigment epithelium (RPE) is involved in the pathogenesis of retinal diseases and is a key target for a number of gene-based therapeutics. In this study, we addressed the inherent drawbacks of non-viral gene vectors and combined different approaches to design an efficient and safe dendrimer-based gene-delivery platform for delivery to human RPE cells. We used hydroxyl-terminated polyamidoamine (PAMAM) dendrimers functionalized with various amounts of amine groups to achieve effective plasmid compaction. We further used triamcinolone acetonide (TA) as a nuclear localization enhancer for the dendrimer-gene complex and achieved significant improvement in cell uptake and transfection of hard-to-transfect human RPE cells. To improve colloidal stability, we further shielded the gene vector surface through incorporation of PEGylated dendrimer along with dendrimer-TA for DNA complexation. The resultant complexes showed improved stability while minimally affecting transgene delivery, thus improving the translational relevance of this platform.Ocular gene therapy holds promise for the treatment of numerous blinding disorders. Despite the significant progress in the field of viral and non-viral gene delivery to the eye, significant obstacles remain in the way of achieving high-level transgene expression without adverse effects. The retinal pigment epithelium (RPE) is involved in the pathogenesis of retinal diseases and is a key target for a number of gene-based therapeutics. In this study, we addressed the inherent drawbacks of non-viral gene vectors and combined different approaches to design an efficient and safe dendrimer-based gene-delivery platform for delivery to human RPE

  19. An investigation into the role of dendrimers as potential enhancers of the dermal delivery of topically applied chlorhexidine

    OpenAIRE

    Judd, Amy Maryanne

    2013-01-01

    The reduction of bacteria on the skin results in prophylactic and therapeutic benefits by reducing the occurrence of skin infections. Currently, chlorhexidine digluconate, a conventional topical antiseptic, permeates the skin poorly leaving viable opportunistic pathogens below the superficial layers of the stratum corneum. The aim of this study was to use polyamidoamine (PAMAM) dendrimers to enhance the topical delivery of chlorhexidine digluconate to improve its antimicrobial efficacy.

  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-m...

  1. 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.

  2. 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...

  3. In vivo toxicity evaluation of gold-dendrimer composite nanodevices with different surface charges.

    Science.gov (United States)

    Kasturirangan, Venugopalan; Nair, Bindu M; Kariapper, Muhammed T S; Lesniak, Wojciech G; Tan, Wei; Bizimungu, Remy; Kanter, Peter; Toth, Karoly; Buitrago, Sandra; Rustum, Youcef M; Hutson, Alan; Balogh, Lajos P; Khan, Mohamed K

    2013-06-01

    Composite nanodevices (CNDs) are multifunctional nanomaterials with potential uses in cancer imaging and therapy. Poly(amidoamine) dendrimer-based composite nanodevices are important members of this group and consist of an organic dendrimer component and an incorporated inorganic component, in this case, gold. This study addresses the short- (14 days) and long-term (78 days) in vivo toxicity of generation-5 (G5; 5 nm) PAMAM dendrimer-based gold-CNDs (Au-CNDs) with varying surface charges (positive, negative and neutral) in C57BL/6J male mice. Detailed toxicological analyses of (1) body weight changes, (2) serum chemistry and (3) histopathological examination of 22 organs showed no evidence of organ injury or organ function compromise. Zeta potential of Au-CNDs showed significant change from their parent dendrimers upon gold incorporation, making the normally lethal positive surface dendrimer biologically safe. Also homeostatic mechanisms in vivo may compensate/repair toxic effects, something not seen with in vitro assays.

  4. Biomimetics: From Bioinformatics to Rational Design of Dendrimers as Gene Carriers.

    Directory of Open Access Journals (Sweden)

    Valeria Márquez-Miranda

    Full Text Available Biomimetics, or the use of principles of Nature for developing new materials, is a paradigm that could help Nanomedicine tremendously. One of the current challenges in Nanomedicine is the rational design of new efficient and safer gene carriers. Poly(amidoamine (PAMAM dendrimers are a well-known class of nanoparticles, extensively used as non-viral nucleic acid carriers, due to their positively charged end-groups. Yet, there are still several aspects that can be improved for their successful application in in vitro and in vivo systems, including their affinity for nucleic acids as well as lowering their cytotoxicity. In the search of new functional groups that could be used as new dendrimer-reactive groups, we followed a biomimetic approach to determine the amino acids with highest prevalence in protein-DNA interactions. Then we introduced them individually as terminal groups of dendrimers, generating a new class of nanoparticles. Molecular dynamics studies of two systems: PAMAM-Arg and PAMAM-Lys were also performed in order to describe the formation of complexes with DNA. Results confirmed that the introduction of amino acids as terminal groups in a dendrimer increases their affinity for DNA and the interactions in the complexes were characterized at atomic level. We end up by briefly discussing additional modifications that can be made to PAMAM dendrimers to turned them into promising new gene carriers.

  5. Biomimetics: From Bioinformatics to Rational Design of Dendrimers as Gene Carriers

    Science.gov (United States)

    Araya-Durán, Ingrid; Varas-Concha, Ignacio; Almonacid, Daniel Eduardo; González-Nilo, Fernando Danilo

    2015-01-01

    Biomimetics, or the use of principles of Nature for developing new materials, is a paradigm that could help Nanomedicine tremendously. One of the current challenges in Nanomedicine is the rational design of new efficient and safer gene carriers. Poly(amidoamine) (PAMAM) dendrimers are a well-known class of nanoparticles, extensively used as non-viral nucleic acid carriers, due to their positively charged end-groups. Yet, there are still several aspects that can be improved for their successful application in in vitro and in vivo systems, including their affinity for nucleic acids as well as lowering their cytotoxicity. In the search of new functional groups that could be used as new dendrimer-reactive groups, we followed a biomimetic approach to determine the amino acids with highest prevalence in protein-DNA interactions. Then we introduced them individually as terminal groups of dendrimers, generating a new class of nanoparticles. Molecular dynamics studies of two systems: PAMAM-Arg and PAMAM-Lys were also performed in order to describe the formation of complexes with DNA. Results confirmed that the introduction of amino acids as terminal groups in a dendrimer increases their affinity for DNA and the interactions in the complexes were characterized at atomic level. We end up by briefly discussing additional modifications that can be made to PAMAM dendrimers to turned them into promising new gene carriers. PMID:26382062

  6. Dendronization of gold and CdSe/cdS (core-shell) quantum dots with tomalia type, thiol core, functionalized poly(amidoamine) (PAMAM) dendrons

    International Nuclear Information System (INIS)

    Poly(amidoamine) (PAMAM) dendrimers containing disulfide cores (i.e., cystamine) and possessing carboxylic acid or hydroxyl terminal groups were reduced with dithiothreitol (DTT) to yield single site, thiol core, functionalized PAMAM dendron reagents. These thiol functionalized dendron reagents were used to surface modify (dendronize) both gold nanoparticles, as well as CdSe/CdS (core-shell) quantum dots (QDs). Dendronization involved self-assembly of the focal point thiol functional dendrons at the metal interface of both gold and CdSe/CdS QDs by ligand exchange of protective surfactants used for their synthesis. The synthesis, characterization and preliminary luminescence studies of these new dendritic hybrids are reported

  7. 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 ...

  8. In Situ X-ray Absorption Analysis of ~1.8 nm Dendrimer-Encapsulated Platinum Nanoparticles During Electrochemical CO Oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Weir, M.; Myers, V; Frenkel, A; Crooks, R

    2010-01-01

    We report an in situ X-ray absorption-fine structure (XAFS) spectroscopic analysis of {approx}1.8 nm Pt dendrimer-encapsulated nanoparticles (DENs) during electrocatalytic oxidation of CO. The results indicate that Pt nanoparticles encapsulated within poly(amidoamine) (PAMAM) dendrimers and immobilized on a carbon electrode retain their electrocatalytic activity and are structurally stable for extended periods during CO oxidation. This is a significant finding, because nanoparticles in this size range are good experimental models for comparison to first-principles calculations if they remain stable.

  9. Research on the Resistance of Four Polyamidoamine Dendrimers Formula-tion in Reversing Human Breast Carcinoma MCF-7/ADR Cells to Adriacin%四种聚酰胺-胺树状大分子制剂逆转人乳腺癌MCF-7/ADR细胞对阿霉素耐药性的研究

    Institute of Scientific and Technical Information of China (English)

    孙冬妮; 牛垒

    2016-01-01

    目的:探讨带有不同电荷及配体的树状大分子(PAMAM)对逆转人乳腺癌MCF-7/ADR细胞多药耐药(MDR)的影响。方法以阿霉素为模型药,比较了四种载药大分子(G 3.5/DOX,G 4.0/DOX,PEG-G 4.0/DOX,FA-G 4.0/DOX)对MCF-7/ADR细胞的细胞毒作用。结果四种大分子制剂的细胞毒均高于DOX溶液,FA-G 4.0(6.74滋g/mL)最强,其逆转倍数达到5.07。与大分子制剂孵育2 h后,MCF-7/ADR细胞中阿霉素浓度大小为FA-G 4.0/DOX 跃 G 4.0/DOX抑 G 3.5/DOX跃PEG-G 4.0/DOX跃DOX溶液。结论四种大分子制剂均可一定程度地克服MCF/ADR细胞的耐药性,G 3.5/DOX、G 4.0/DOX、PEG-G 4.0/DOX对MDR的影响没有显著区别,FA-G 4.0/DOX克服MDR的效果最好。%Objective To study the effect of dendrimers with different charges and ligands on the multidrug resistance of re-versing human breast carcinoma MCF-7/ADR cells. Methods The cytotoxic effects of four drug loaded macromoleculars (G 3.5/DOX, G 4.0/DOX, PEG-G 4.0/DOX, FA-G 4.0/DOX) on the MCF-7/ADR cell were compared by taking adriacin as model drugs. Results The cellular poison formulated by four macromoleculars was higher than DOX solution, and FA-G 4.0 (6.74 μg/mL) was the strongest, and its reversal index reached 5.07, after 2h incubation of macromolecular formulation, the adriacin concentration in MCF-7/ADR cell was FA-G 4.0/DOX >G 4.0/DOX- G 3.5/DOX >PEG-G 4.0/DOX>DOX so-lution. Conclusion Four macromolecular formulations can overcome the resistance of MCF/ADR cells to a certain degree, and there is no obvious difference in the effect of G 3.5/DOX, G 4.0/DOX, PEG-G 4.0/DOX on MDR, and the effect of FA-G 4.0/DOX in overcoming MDR is the best.

  10. Covalent immobilization of invertase on PAMAM-dendrimer modified superparamagnetic iron oxide nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Uzun, K.; Cevik, E.; Senel, M., E-mail: msenel@fatih.edu.t [Fatih University, Department of Chemistry, Faculty of Arts and Sciences (Turkey); Soezeri, H. [TUBITAK-UME, National Metrology Institute (Turkey); Baykal, A. [Fatih University, Department of Chemistry, Faculty of Arts and Sciences (Turkey); Abasiyanik, M. F. [Fatih University, Department of Genetics and Bioengineering, Faculty of Engineering (Turkey); Toprak, M. S. [Royal Institute of Technology-KTH, Department of Functional Materials (Sweden)

    2010-10-15

    In this study, polyamidoamine (PAMAM) dendrimer was synthesized on the surface of superparamagnetite nanoparticles to enhance invertase immobilization. The amount of immobilized enzyme on the surface-hyperbranched magnetite nanoparticle was up to 2.5 times (i.e., 250%) as much as that of magnetite nanoparticle modified with only amino silane. Maximum reaction rate (V{sub max}) and Michaelis-Menten constant (K{sub m}) were determined for the free and immobilized enzymes. Various characteristics of immobilized invertase such as; the temperature activity, thermal stability, operational stability, and storage stability were evaluated and results revealed that stability of the enzyme is improved upon immobilization.

  11. 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

  12. Thermoregulated Coacervation, Metal-Encapsulation and Nanoparticle Synthesis in Novel Triazine Dendrimers.

    Science.gov (United States)

    Ramírez-Crescencio, Fermín; Enciso, Alan E; Hasan, Mirza; da Costa, Viviana C P; Annunziata, Onofrio; Redón, Rocío; Coffer, Jeffery L; Simanek, Eric E

    2016-01-01

    The synthesis and solubility behaviors of four generation five (G5) triazine dendrimers are studied. While the underivatized cationic dendrimer is soluble in water, the acetylated and propanoylated derivatives undergo coacervation in water upon increasing temperature. Occurring around room temperature, this behavior is related to a liquid-liquid phase transition with a lower critical solution temperature (LCST) and is explained by differences in composition, notably, the hydrophobic nature of the terminal groups. Interestingly, the water solubility of the acetylated dendrimer is affected by the addition of selected metal ions. Titrating solutions of acetylated dendrimer at temperatures below the LCST with gold or palladium ions promoted precipitation, but platinum, iridium, and copper did not. Gold nanoparticles having diameters of 2.5 ± 0.8 nm can be obtained from solutions of the acetylated dendrimer at concentrations of gold less than that required to induce precipitation by treating the solution with sodium borohydride. PMID:27187331

  13. Thermoregulated Coacervation, Metal-Encapsulation and Nanoparticle Synthesis in Novel Triazine Dendrimers

    Directory of Open Access Journals (Sweden)

    Fermín Ramírez-Crescencio

    2016-05-01

    Full Text Available The synthesis and solubility behaviors of four generation five (G5 triazine dendrimers are studied. While the underivatized cationic dendrimer is soluble in water, the acetylated and propanoylated derivatives undergo coacervation in water upon increasing temperature. Occurring around room temperature, this behavior is related to a liquid-liquid phase transition with a lower critical solution temperature (LCST and is explained by differences in composition, notably, the hydrophobic nature of the terminal groups. Interestingly, the water solubility of the acetylated dendrimer is affected by the addition of selected metal ions. Titrating solutions of acetylated dendrimer at temperatures below the LCST with gold or palladium ions promoted precipitation, but platinum, iridium, and copper did not. Gold nanoparticles having diameters of 2.5 ± 0.8 nm can be obtained from solutions of the acetylated dendrimer at concentrations of gold less than that required to induce precipitation by treating the solution with sodium borohydride.

  14. 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.

  15. Dendrimer-Linked Antifreeze Proteins Have Superior Activity and Thermal Recovery.

    Science.gov (United States)

    Stevens, Corey A; Drori, Ran; Zalis, Shiran; Braslavsky, Ido; Davies, Peter L

    2015-09-16

    By binding to ice, antifreeze proteins (AFPs) depress the freezing point of a solution and inhibit ice recrystallization if freezing does occur. Previous work showed that the activity of an AFP was incrementally increased by fusing it to another protein. Even larger increases in activity were achieved by doubling the number of ice-binding sites by dimerization. Here, we have combined the two strategies by linking multiple outward-facing AFPs to a dendrimer to significantly increase both the size of the molecule and the number of ice-binding sites. Using a heterobifunctional cross-linker, we attached between 6 and 11 type III AFPs to a second-generation polyamidoamine (G2-PAMAM) dendrimer with 16 reactive termini. This heterogeneous sample of dendrimer-linked type III constructs showed a greater than 4-fold increase in freezing point depression over that of monomeric type III AFP. This multimerized AFP was particularly effective at ice recrystallization inhibition activity, likely because it can simultaneously bind multiple ice surfaces. Additionally, attachment to the dendrimer has afforded the AFP superior recovery from heat denaturation. Linking AFPs together via polymers can generate novel reagents for controlling ice growth and recrystallization. PMID:26267368

  16. Dendrimer-Linked Antifreeze Proteins Have Superior Activity and Thermal Recovery.

    Science.gov (United States)

    Stevens, Corey A; Drori, Ran; Zalis, Shiran; Braslavsky, Ido; Davies, Peter L

    2015-09-16

    By binding to ice, antifreeze proteins (AFPs) depress the freezing point of a solution and inhibit ice recrystallization if freezing does occur. Previous work showed that the activity of an AFP was incrementally increased by fusing it to another protein. Even larger increases in activity were achieved by doubling the number of ice-binding sites by dimerization. Here, we have combined the two strategies by linking multiple outward-facing AFPs to a dendrimer to significantly increase both the size of the molecule and the number of ice-binding sites. Using a heterobifunctional cross-linker, we attached between 6 and 11 type III AFPs to a second-generation polyamidoamine (G2-PAMAM) dendrimer with 16 reactive termini. This heterogeneous sample of dendrimer-linked type III constructs showed a greater than 4-fold increase in freezing point depression over that of monomeric type III AFP. This multimerized AFP was particularly effective at ice recrystallization inhibition activity, likely because it can simultaneously bind multiple ice surfaces. Additionally, attachment to the dendrimer has afforded the AFP superior recovery from heat denaturation. Linking AFPs together via polymers can generate novel reagents for controlling ice growth and recrystallization.

  17. Amine functionalization of cholecyst-derived extracellular matrix with generation 1 PAMAM dendrimer.

    LENUS (Irish Health Repository)

    Chan, Jeffrey C Y

    2008-02-01

    A method to functionalize cholecyst-derived extracellular matrix (CEM) with free amine groups was established in an attempt to improve its potential for tethering of bioactive molecules. CEM was incorporated with Generation-1 polyamidoamine (G1 PAMAM) dendrimer by using N-(3-dimethylaminopropyl)-N\\'-ethylcarbodiimide and N-hydroxysuccinimide cross-linking system. The nature of incorporation of PAMAM dendrimer was evaluated using shrink temperature measurements, Fourier transform infrared (FTIR) assessment, ninhydrin assay, and swellability. The effects of PAMAM incorporation on mechanical and degradation properties of CEM were evaluated using a uniaxial mechanical test and collagenase degradation assay, respectively. Ninhydrin assay and FTIR assessment confirmed the presence of increasing free amine groups with increasing quantity of PAMAM in dendrimer-incorporated CEM (DENCEM) scaffolds. The amount of dendrimer used was found to be critical in controlling scaffold degradation, shrink temperature, and free amine content. Cell culture studies showed that fibroblasts seeded on DENCEM maintained their metabolic activity and ability to proliferate in vitro. In addition, fluorescence cell staining and scanning electron microscopy analysis of cell-seeded DENCEM showed preservation of normal fibroblast morphology and phenotype.

  18. Mechanism of Cooperativity and Nonlinear Release Kinetics in Multivalent Dendrimer-Atropine Complexes.

    Science.gov (United States)

    Mukherjee, Jhindan; Wong, Pamela T; Tang, Shengzhuang; Gam, Kristina; Coulter, Alexa; Baker, James R; Choi, Seok Ki

    2015-12-01

    Despite extensive studies on drug delivery using multivalent complexation systems, the biophysical basis for release kinetics remains poorly defined. The present study addresses this aspect involved in the complexation of a fifth generation poly(amidoamine) (PAMAM) dendrimer with atropine, an essential antidote used for treating organophosphate poisoning. First, we designed (1)H NMR titration studies for determining the molecular basis of the drug complexation with a glutarate-modified anionic dendrimer. These provide evidence pointing to a combination of electrostatic and hydrophobic interactions as the driving forces for dendrimer complexation with the alkaloid drug molecule. Second, using LC-MS/MS spectrometry, we determined the dissociation constants (KD) at steady state and also measured the drug release kinetics of atropine complexes with four negatively charged dendrimer types. Each of these dendrimers has a high payload capacity for up to ∼ 100 atropine molecules. However, the affinity of the atropine to the carrier was highly dependent on the drug to dendrimer ratio. Thus, a complex made at a lower loading ratio (≤ 0.1) displayed greater atropine affinity (KD ≈ μM) than other complexes prepared at higher ratios (>10), which showed only mM affinity. This negative cooperative variation in affinity is tightly associated with the nonlinear release kinetics observed for each complex in which drug release occurs more slowly at the later time phase at a lower loading ratio. In summary, the present study provides novel insights on the cooperativity as the mechanistic basis for nonlinear release kinetics observed in multivalent carrier systems. PMID:26485315

  19. Mechanism of Cooperativity and Nonlinear Release Kinetics in Multivalent Dendrimer-Atropine Complexes.

    Science.gov (United States)

    Mukherjee, Jhindan; Wong, Pamela T; Tang, Shengzhuang; Gam, Kristina; Coulter, Alexa; Baker, James R; Choi, Seok Ki

    2015-12-01

    Despite extensive studies on drug delivery using multivalent complexation systems, the biophysical basis for release kinetics remains poorly defined. The present study addresses this aspect involved in the complexation of a fifth generation poly(amidoamine) (PAMAM) dendrimer with atropine, an essential antidote used for treating organophosphate poisoning. First, we designed (1)H NMR titration studies for determining the molecular basis of the drug complexation with a glutarate-modified anionic dendrimer. These provide evidence pointing to a combination of electrostatic and hydrophobic interactions as the driving forces for dendrimer complexation with the alkaloid drug molecule. Second, using LC-MS/MS spectrometry, we determined the dissociation constants (KD) at steady state and also measured the drug release kinetics of atropine complexes with four negatively charged dendrimer types. Each of these dendrimers has a high payload capacity for up to ∼ 100 atropine molecules. However, the affinity of the atropine to the carrier was highly dependent on the drug to dendrimer ratio. Thus, a complex made at a lower loading ratio (≤ 0.1) displayed greater atropine affinity (KD ≈ μM) than other complexes prepared at higher ratios (>10), which showed only mM affinity. This negative cooperative variation in affinity is tightly associated with the nonlinear release kinetics observed for each complex in which drug release occurs more slowly at the later time phase at a lower loading ratio. In summary, the present study provides novel insights on the cooperativity as the mechanistic basis for nonlinear release kinetics observed in multivalent carrier systems.

  20. A functionalized fluorescent dendrimer as a pesticide nanocarrier: application in pest control

    Science.gov (United States)

    Liu, Xiaoxia; He, Bicheng; Xu, Zejun; Yin, Meizhen; Yang, Wantai; Zhang, Huaijiang; Cao, Jingjun; Shen, Jie

    2014-12-01

    We report the delivery of a hydrophobic pesticide, thiamethoxam, by water-soluble nanosized cationic dendrimers that contain hydrophobic dendritic polyesters and peripheral amines, demonstrated by DLS, spectral analysis and ITC. The dendrimer-based nanocarrier can efficiently deliver the pesticide into the live cells and largely increase the cytotoxicity of the drug.We report the delivery of a hydrophobic pesticide, thiamethoxam, by water-soluble nanosized cationic dendrimers that contain hydrophobic dendritic polyesters and peripheral amines, demonstrated by DLS, spectral analysis and ITC. The dendrimer-based nanocarrier can efficiently deliver the pesticide into the live cells and largely increase the cytotoxicity of the drug. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr05733c

  1. Thermoregulated Coacervation, Metal-Encapsulation and Nanoparticle Synthesis in Novel Triazine Dendrimers

    OpenAIRE

    Fermín Ramírez-Crescencio; Alan E. Enciso; Mirza Hasan; da Costa, Viviana C.P.; Onofrio Annunziata; Rocío Redón; Jeffery L. Coffer; Simanek, Eric E.

    2016-01-01

    The synthesis and solubility behaviors of four generation five (G5) triazine dendrimers are studied. While the underivatized cationic dendrimer is soluble in water, the acetylated and propanoylated derivatives undergo coacervation in water upon increasing temperature. Occurring around room temperature, this behavior is related to a liquid-liquid phase transition with a lower critical solution temperature (LCST) and is explained by differences in composition, notably, the hydrophobic nature of...

  2. Supramolecular Organization of Functional Dendrimers

    Institute of Scientific and Technical Information of China (English)

    D.Guillon; B.Donnio

    2007-01-01

    1 Results The possibility to develop large multifunctional macromolecular structures which can further self-assemble into nanosized objects,makes liquid-crystalline dendrimers highly attractive candidates in the field of materials science and may represent an original strategy for the realisation of molecular electronic-based devices[1-2].Sophisticated nanostructures obtained with dendrimers where mesogenic groups are not only located at the periphery of the dendrimer[3] but also at the branching points...

  3. Photophysical studies of the interactions of poly(amidoamine) generation zero (PAMAM G0) with copper and zinc ions

    Energy Technology Data Exchange (ETDEWEB)

    López-Cabaña, Z.E. [Laboratory of Asymmetric Synthesis, Chemistry Institute of Natural Resources, University of Talca (Chile); Valdés, O. [Nanobiotechnology Division at University of Talca, Fraunhofer Chile Research Foundation – Center for Systems Biotechnology, FCR-CSB, P.O. Box 747 Talca (Chile); Vergara, C.E. [Laboratory of Asymmetric Synthesis, Chemistry Institute of Natural Resources, University of Talca (Chile); Camarada, M.B. [Universidad Andrés Bello, Facultad de Biología, Center for Bioinformatics and Integrative Biology (CBIB), República 239, Santiago (Chile); Fundación Fraunhofer Chile Research, M. Sánchez Fontecilla 310 piso 14, Las Condes (Chile); Nachtigall, F.M. [Nanobiotechnology Division at University of Talca, Fraunhofer Chile Research Foundation – Center for Systems Biotechnology, FCR-CSB, P.O. Box 747 Talca (Chile); González-Nilo, F.D. [Universidad Andrés Bello, Facultad de Biología, Center for Bioinformatics and Integrative Biology (CBIB), República 239, Santiago (Chile); Fundación Fraunhofer Chile Research, M. Sánchez Fontecilla 310 piso 14, Las Condes (Chile); Santos, Leonardo S., E-mail: lssantos@utalca.cl [Laboratory of Asymmetric Synthesis, Chemistry Institute of Natural Resources, University of Talca (Chile); Nanobiotechnology Division at University of Talca, Fraunhofer Chile Research Foundation – Center for Systems Biotechnology, FCR-CSB, P.O. Box 747 Talca (Chile)

    2015-08-15

    This study reports the photophysical behavior of poly(amidoamine) generation zero (PAMAM G0) in the presence of Cu(II) and Zn(II) ions in aqueous solutions using absorption and fluorescence spectroscopy. Theoretical and experimental results confirmed the presence of a strong covalent metal–ligand interaction between PAMAM G0 and copper ion that favored the formation of a ligand–metal charge transfer band coordination complex. In the case of Zn(II), no complex formation with PAMAM G0 was registered. Structure analysis identified the presence of aggregate like PAMAM G0–Zn moieties that generated an enhancement in the fluorescence emission of PAMAM G0. - Highlights: • Photophysical behavior of PAMAM G0 dendrimer with Cu and Zn ions was studied. • Strong covalent metal–ligand interaction was confirmed between PAMAM G0–Cu(II). • No complex formation with PAMAM G0 was registered in the case of Zn(II). • Dendrimer aggregate generated an enhancement in fluorescence emission.

  4. Photophysical studies of the interactions of poly(amidoamine) generation zero (PAMAM G0) with copper and zinc ions

    International Nuclear Information System (INIS)

    This study reports the photophysical behavior of poly(amidoamine) generation zero (PAMAM G0) in the presence of Cu(II) and Zn(II) ions in aqueous solutions using absorption and fluorescence spectroscopy. Theoretical and experimental results confirmed the presence of a strong covalent metal–ligand interaction between PAMAM G0 and copper ion that favored the formation of a ligand–metal charge transfer band coordination complex. In the case of Zn(II), no complex formation with PAMAM G0 was registered. Structure analysis identified the presence of aggregate like PAMAM G0–Zn moieties that generated an enhancement in the fluorescence emission of PAMAM G0. - Highlights: • Photophysical behavior of PAMAM G0 dendrimer with Cu and Zn ions was studied. • Strong covalent metal–ligand interaction was confirmed between PAMAM G0–Cu(II). • No complex formation with PAMAM G0 was registered in the case of Zn(II). • Dendrimer aggregate generated an enhancement in fluorescence emission

  5. Chemistry of Secondary Metabolites (Production, Properties, Biological Activity, etc.: Solubility Study of the Interaction between Pamam G-3 Dendrimer and 5 Fluorouracil in Aqueous Solution

    Directory of Open Access Journals (Sweden)

    B. PALECZ

    2014-06-01

    Full Text Available Poly(amidoamine dendrimers (PAMAM are polymeric macromolecules that can find their use as carriers of small ligand molecules such as cosmetics and drugs. 5- Fluorouracil is a potent oncological drug, whose usage is limited because of its relatively high toxicity.The surface and internal layer groups in PAMAM dendrimer belonging to the third (G3 generation create an open-type structure, which facilitate small ligand molecules to bind with them.The formation equilibrium of PAMAM G3 dendrimer complex with an oncologic drug such as 5 fluorouracil (FU in water at room temperature was examined. Using the results of the drug solubility in dendrimer solutions, the maximal number of drug molecules in the dendrimer-drug complex was evaluated. Solubility results show that PAMAM G3 dendrimer can transfer tens 5 fluorouracil molecules in aqueous solution.This research work was funded from the Polish budget appropriations for science in the years 2013-2015, project number IP2012 022372.

  6. Complexation Between Weakly Basic Dendrimers and Linear Polyelectrolytes: Effects of Chain Stiffness, Grafts, and pOH

    Science.gov (United States)

    Lewis, Thomas; Pandav, Gunja; Omar, Ahmad; Ganesan, Venkat

    2013-03-01

    The unique architecture and high charge density of dendrimer molecules have attracted interest for their utilization in gene delivery applications. The strong binding affinity of cationic dendrimers to genetic materials make them effective gene delivery vectors not only by shielding the nucleic acid (NA) material from degradative enzymes in the blood stream, but also by reducing the overall negative charge of the dendrimer-NA material complex, which in turn creates more favorable interaction with the anionic cell membrane. However, the high cytotoxicities of cationic dendrimers have motivated the development of polyethylene glycol (PEG) conjugated dendrimer molecules, which have been shown to reduce dendrimer cytotoxicity while still retaining transfection ability. In order to gain insight into how the addition of neutral grafts affects the binding affinity and conformations of dendrimer-NA material complexes, we have developed and numerically solved a Self-Consistent Field Theory approach for both grafted and non-grafted annealed charged dendrimer molecules in the presence of linear polyelectrolyte molecules. Specifically, this work examines the effect of linear polyelectrolyte stiffness, grafting chain length, and solution pOH.

  7. Hollow spherical supramolecular dendrimers.

    Science.gov (United States)

    Percec, Virgil; Peterca, Mihai; Dulcey, Andrés E; Imam, Mohammad R; Hudson, Steven D; Nummelin, Sami; Adelman, Peter; Heiney, Paul A

    2008-10-01

    The synthesis of a library containing 12 conical dendrons that self-assemble into hollow spherical supramolecular dendrimers is reported. The design principles for this library were accessed by development of a method that allows the identification of hollow spheres, followed by structural and retrostructural analysis of their Pm3n cubic lattice. The first hollow spherical supramolecular dendrimer was made by replacing the tapered dendron, from the previously reported tapered dendritic dipeptide that self-assembled into helical pores, with its constitutional isomeric conical dendron. This strategy generated a conical dendritic dipeptide that self-assembled into a hollow spherical supramolecular dendrimer that self-organizes in a Pm3n cubic lattice. Other examples of hollow spheres were assembled from conical dendrons without a dipeptide at their apex. These are conical dendrons originated from tapered dendrons containing additional benzyl ether groups at their apex. The inner part of the hollow sphere assembled from the dipeptide resembles the path of a spherical helix or loxodrome and, therefore, is chiral. The spheres assembled from other conical dendrons are nonhelical, even when they contain stereocenters on the alkyl groups from their periphery. Functionalization of the apex of the conical dendrons with diethylene glycol allowed the encapsulation of LiOTf and RbOTf in the center of the hollow sphere. These experiments showed that hollow spheres function as supramolecular dendritic capsules and therefore are expected to display functions complementary to those of other related molecular and supramolecular structures. PMID:18771261

  8. 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...

  9. Precise Synthesis of Organometallic Dendrimers

    Institute of Scientific and Technical Information of China (English)

    K. Onitsuka; S. Takahashi

    2005-01-01

    @@ 1Introduction Dendrimers possessing a regularly branched architecture and large spherical dimensions have attracted significant attention because of their unique and tunable properties as well as their potential applications. The incorporation of organometallic species into dendritic molecules has been attracting much attention, because the addition of properties characteristic of organometallic complexes, such as magnetic, electronic, and photo-optical properties, as well as reactivity may lead to the realization of new functionalized dendrimers. Although there are many examples of organometallic dendrimers that contain metallic species at the core or at the periphery, dendrimers composed of organometallic complexes in each generation are still limited. We present here convergent and divergent approaches to novel organometallic dendrimers, of which the skeletons were built up with platinum-acetylide units.

  10. 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

  11. Neutron Reflectometry Investigations of the Interaction of DNA-PAMAM Dendrimers with Model Biological Membranes

    International Nuclear Information System (INIS)

    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)

  12. Charge-dependent conformations and dynamics of pamam dendrimers revealed by neutron scattering and molecular dynamics

    Science.gov (United States)

    Wu, Bin

    Neutron scattering and fully atomistic molecular dynamics (MD) are employed to investigate the structural and dynamical properties of polyamidoamine (PAMAM) dendrimers with ethylenediamine (EDA) core under various charge conditions. Regarding to the conformational characteristics, we focus on scrutinizing density profile evolution of PAMAM dendrimers as the molecular charge of dendrimer increases from neutral state to highly charged condition. It should be noted that within the context of small angle neutron scattering (SANS), the dendrimers are composed of hydrocarbon component (dry part) and the penetrating water molecules. Though there have been SANS experiments that studied the charge-dependent structural change of PAMAM dendrimers, their results were limited to the collective behavior of the aforementioned two parts. This study is devoted to deepen the understanding towards the structural responsiveness of intra-molecular polymeric and hydration parts separately through advanced contrast variation SANS data analysis scheme available recently and unravel the governing principles through coupling with MD simulations. Two kinds of acids, namely hydrochloric and sulfuric acids, are utilized to tune the pH condition and hence the molecular charge. As far as the dynamical properties, we target at understanding the underlying mechanism that leads to segmental dynamic enhancement observed from quasielstic neutron scattering (QENS) experiment previously. PAMAM dendrimers have a wealth of potential applications, such as drug delivery agency, energy harvesting medium, and light emitting diodes. More importantly, it is regarded as an ideal system to test many theoretical predictions since dendrimers conjugate both colloid-like globular shape and polymer-like flexible chains. This Ph.D. research addresses two main challenges in studying PAMAM dendrimers. Even though neutron scattering is an ideal tool to study this PAMAM dendrimer solution due to its matching temporal and

  13. Metallocenyl dendrimers and their applications in molecular electronics, sensing, and catalysis.

    Science.gov (United States)

    Astruc, Didier; Ornelas, Cátia; Ruiz, Jaime

    2008-07-01

    We have investigated the movement of electrons around the peripheries of dendrimers and between their redox termini and electrodes through studies of the electrochemistry of dendrimers presenting metallocenes (and other transition metal sandwich complexes) as terminal groups. Because these compounds can be stabilized in both their oxidized and their reduced forms, their electrochemical and chemical redox processes proceed without decomposition (chemical reversibility). Most interestingly, electrochemical studies reveal that electron transfer within the dendrimers and between the dendrimers and electrodes are both very fast processes when the branches are flexible (electrochemical reversibility). When the dendrimer branches are sufficiently long, the redox events at the many termini of the metallodendrimer are independent, appearing as a single wave in the cyclic voltammogram, because of very weak electrostatic effects. As a result, these metallodendrimers have applications in the molecular recognition, sensing, and titration of anions (e.g., ATP(2-)) and cations (e.g., transition metal complexes). When the recognition properties are coupled with catalysis, the metallodendrimers function in an enzyme-like manner. For example, Pd(II) can be recognized and titrated using the dendrimer's terminal redox centers and internal coordinate ligands. Redox control over the number of Pd(II) species located within a dendrimer allows us to predetermine the number of metal atoms that end up in the form of a dendrimer-encapsulated Pd nanoparticle (PdNP). For hydrogenation of olefins, the efficiency (turnover frequency, TOF) and stability (turnover number, TON) depend on the size of the dendrimer-encapsulated PdNP catalysts, similar to the behavior of polymer-supported PdNP catalysts, suggesting a classic mechanism in which all of the steps proceed on the PdNP surface. On the other hand, Miyaura-Suzuki carbon-carbon bond-forming reactions catalyzed by dendrimer-encapsulated Pd

  14. Dendrimer mediated clustering of bacteria: improved aggregation and evaluation of bacterial response and viability.

    Science.gov (United States)

    Leire, Emma; Amaral, Sandra P; Louzao, Iria; Winzer, Klaus; Alexander, Cameron; Fernandez-Megia, Eduardo; Fernandez-Trillo, Francisco

    2016-06-24

    Here, we evaluate how cationic gallic acid-triethylene glycol (GATG) dendrimers interact with bacteria and their potential to develop new antimicrobials. We demonstrate that GATG dendrimers functionalised with primary amines in their periphery can induce the formation of clusters in Vibrio harveyi, an opportunistic marine pathogen, in a generation dependent manner. Moreover, these cationic GATG dendrimers demonstrate an improved ability to induce cluster formation when compared to poly(N-[3-(dimethylamino)propyl]methacrylamide) [p(DMAPMAm)], a cationic linear polymer previously shown to cluster bacteria. Viability of the bacteria within the formed clusters and evaluation of quorum sensing controlled phenotypes (i.e. light production in V. harveyi) suggest that GATG dendrimers may be activating microbial responses by maintaining a high concentration of quorum sensing signals inside the clusters while increasing permeability of the microbial outer membranes. Thus, the reported GATG dendrimers constitute a valuable platform for the development of novel antimicrobial materials that can target microbial viability and/or virulence. PMID:27127812

  15. Modular Integration of Upconverting Nanocrystal-Dendrimer Composites for Folate Receptor-Specific NIR Imaging and Light-Triggered Drug Release.

    Science.gov (United States)

    Wong, Pamela T; Chen, Dexin; Tang, Shengzhuang; Yanik, Sean; Payne, Michael; Mukherjee, Jhindan; Coulter, Alexa; Tang, Kenny; Tao, Ke; Sun, Kang; Baker, James R; Choi, Seok Ki

    2015-12-01

    Upconversion nanocrystals (UCNs) display near-infrared (NIR)-responsive photoluminescent properties for NIR imaging and drug delivery. The development of effective strategies for UCN integration with other complementary nanostructures for targeting and drug conjugation is highly desirable. This study reports on a core/shell-based theranostic system designed by UCN integration with a folate (FA)-conjugated dendrimer for tumor targeting and with photocaged doxorubicin as a cytotoxic agent. Two types of UCNs (NaYF4:Yb/Er (or Yb/Tm); diameter = ≈50 to 54 nm) are described, each displaying distinct emission properties upon NIR (980 nm) excitation. The UCNs are surface modified through covalent attachment of photocaged doxorubicin (ONB-Dox) and a multivalent FA-conjugated polyamidoamine (PAMAM) dendrimer G5(FA)6 to prepare UCN@(ONB-Dox)(G5FA). Surface plasmon resonance experiments performed with G5(FA)6 dendrimer alone show nanomolar binding avidity (KD = 5.9 × 10(-9) M) to the folate binding protein. This dendrimer binding corresponds with selective binding and uptake of UCN@(ONB-Dox)(G5FA) by FAR-positive KB carcinoma cells in vitro. Furthermore, UCN@(ONB-Dox)(G5FA) treatment of FAR(+) KB cells inhibits cell growth in a light dependent manner. These results validate the utility of modularly integrated UCN-dendrimer nanocomposites for cell type specific NIR imaging and light-controlled drug release, thus serving as a new theranostic system.

  16. Multifunctional dendrimer/combretastatin A4 inclusion complexes enable in vitro targeted cancer therapy

    Directory of Open Access Journals (Sweden)

    Zhang M

    2011-10-01

    Full Text Available Mengen Zhang1,2, Rui Guo2, Yin Wang2, Xueyan Cao2, Mingwu Shen2, Xiangyang Shi1-31State Key Laboratory for Modification of Chemical Fibers and Polymer Materials; 2College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, People’s Republic of China; 3Centro de Química da Madeira, Universidade da Madeira, Campus da Penteada, Funchal, PortugalBackground: We report here a unique approach to using multifunctional dendrimer/combretastatin A4 (CA4 inclusion complexes for targeted cancer therapeutics.Methods: Amine-terminated generation 5 polyamidoamine dendrimers were first partially acetylated to neutralize a significant portion of the terminal amines, and then the remaining dendrimer terminal amines were sequentially modified with fluorescein isothiocyanate as an imaging agent and folic acid as a targeting ligand. The multifunctional dendrimers formed (G5.NHAc-FI-FA were utilized to encapsulate the anticancer drug, CA4, for targeted delivery into cancer cells overexpressing folic acid receptors.Results: The inclusion complexes of G5.NHAc-FI-FA/CA4 formed were stable and are able to significantly improve the water solubility of CA4 from 11.8 to 240 µg/mL. In vitro release studies showed that the multifunctional dendrimers complexed with CA4 could be released in a sustained manner. Both 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide colorimetric assay and morphological cell observation showed that the inhibitory effect of the G5.NHAc-FI-FA/CA4 complexes was similar to that of free CA4 at the same selected drug concentration. More importantly, the complexes were able to target selectively and display specific therapeutic efficacy to cancer cells overexpressing high-affinity folic acid receptors.Conclusion: Multifunctional dendrimers may serve as a valuable carrier to form stable inclusion complexes with various hydrophobic anticancer drugs with improved water solubility, for targeting chemotherapy to

  17. Interfacial Microstructure and Enhanced Mechanical Properties of Carbon Fiber Composites Caused by Growing Generation 1-4 Dendritic Poly(amidoamine) on a Fiber Surface.

    Science.gov (United States)

    Gao, Bo; Zhang, Ruliang; Gao, Fucheng; He, Maoshuai; Wang, Chengguo; Liu, Lei; Zhao, Lifen; Cui, Hongzhi

    2016-08-23

    In an attempt to improve the mechanical properties of carbon fiber composites, propagation of poly(amidoamine) (PAMAM) dendrimers by in situ polymerization on a carbon fiber surface was performed. During polymerization processes, PAMAM was grafted on carbon fiber by repeated Michael addition and amidation reactions. The changes in surface microstructure and the chemical composition of carbon fibers before and after modification were investigated by atomic force microscopy, X-ray photoelectron spectroscopy, and Raman spectroscopy. All the results indicated that PAMAM was successfully grown on the carbon fiber surface. Such propagation could significantly increase the surface roughness and introduce sufficient polar groups onto the carbon fiber surface, enhancing the surface wettability of carbon fiber. The fractured surface of carbon fiber-reinforced composites showed a great enhancement of interfacial adhesion. Compared with those of desized fiber composites, the interlaminar shear strength and interfacial shear strength of PAMAM/fiber-reinforced composites showed increases of 55.49 and 110.94%, respectively.

  18. The Synthesis of G1.0 Poly(amidoamine) Dendrimer (PAMAM) and the Recognition with Anions and Cations%1.0代树形大分子(PAMAM)的合成及对阴阳离子的识别

    Institute of Scientific and Technical Information of China (English)

    董丹丹; 田勋; 马彦青

    2015-01-01

    目前生物体内ATP合酶催化ATP水解的研究是生物催化方向的研究热点.为了探索ATP合酶催化ATP水解的机制,本研究模拟生物体系环境,在N2氛围中,采用甲醇溶液回流的发散合成法合成了多功能化的树形大分子,用核磁、红外光谱等方法对其结构进行了表征,并利用其多作用位点的特征对不同阴阳离子进行了识别作用的分析.结果表明:G1.0 PAMAM(L)与Mn2+的识别效果最明显,荧光强度增加18倍,根据修饰的Benesi-Hildebrand方程得到了G1.0 PAMAM与Mn2+最佳配位比为1:1,结合常数为1.13×104 L/mol;采用Job's法对主客体配位比进行了验证;同时,F-对G1.0 PAMAM荧光猝灭现象最明显,根据修饰的Benesi-Hildebrand方程确定了两者的最佳配位比为1:1,结合常数为2561 L/mol.该结果开辟了新的一类模拟酶催化剂体系,并为研究ATP合酶的作用机理提供理论依据.

  19. Recent Findings Concerning PAMAM Dendrimer Conjugates with Cyclodextrins as Carriers of DNA and RNA

    Directory of Open Access Journals (Sweden)

    Keiichi Motoyama

    2009-08-01

    Full Text Available We have evaluated the potential use of various polyamidoamine (PAMAM dendrimer [dendrimer, generation (G 2-4] conjugates with cyclodextrins (CyDs as novel DNA and RNA carriers. Among the various dendrimer conjugates with CyDs, the dendrimer (G3 conjugate with α-CyD having an average degree of substitution (DS of 2.4 [α-CDE (G3, DS2] displayed remarkable properties as DNA, shRNA and siRNA delivery carriers through the sensor function of α-CDEs toward nucleic acid drugs, cell surface and endosomal membranes. In an attempt to develop cell-specific gene transfer carriers, we prepared sugar-appended α-CDEs. Of the various sugar-appended α-CDEs prepared, galactose- or mannose-appended α-CDEs provided superior gene transfer activity to α-CDE in various cells, but not cell-specific gene delivery ability. However, lactose-appended α-CDE [Lac-α-CDE (G2] was found to possess asialoglycoprotein receptor (AgpR-mediated hepatocyte-selective gene transfer activity, both in vitro and in vivo. Most recently, we prepared folate-poly(ethylene glycol-appended α-CDE [Fol-PαC (G3] and revealed that Fol-PαC (G3 imparted folate receptor (FR-mediated cancer cell-selective gene transfer activity. Consequently, α-CDEs bearing integrated, multifunctional molecules may possess the potential to be novel carriers for DNA, shRNA and siRNA.

  20. Dendrimers and Polyamino-Phenolic Ligands: Activity of New Molecules Against Legionella pneumophila Biofilms

    Science.gov (United States)

    Andreozzi, Elisa; Barbieri, Federica; Ottaviani, Maria F.; Giorgi, Luca; Bruscolini, Francesca; Manti, Anita; Battistelli, Michela; Sabatini, Luigia; Pianetti, Anna

    2016-01-01

    Legionnaires’ disease is a potentially fatal pneumonia caused by Legionella pneumophila, an aquatic bacterium often found within the biofilm niche. In man-made water systems microbial biofilms increase the resistance of legionella to disinfection, posing a significant threat to public health. Disinfection methods currently used in water systems have been shown to be ineffective against legionella over the long-term, allowing recolonization by the biofilm-protected microorganisms. In this study, the anti-biofilm activity of previously fabricated polyamino-phenolic ligands and polyamidoamine dendrimers was investigated against legionella mono-species and multi-species biofilms formed by L. pneumophila in association with other bacteria that can be found in tap water (Aeromonas hydrophila, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae). Bacterial ability to form biofilms was verified using a crystal violet colorimetric assay and testing cell viability by real-time quantitative PCR and Plate Count assay. The concentration of the chemicals tested as anti-biofilm agents was chosen based on cytotoxicity assays: the highest non-cytotoxic chemical concentration was used for biofilm inhibition assays, with dendrimer concentration 10-fold higher than polyamino-phenolic ligands. While Macrophen and Double Macrophen were the most active substances among polyamino-phenolic ligands, dendrimers were overall twofold more effective than all other compounds with a reduction up to 85 and 73% of legionella and multi-species biofilms, respectively. Chemical interaction with matrix molecules is hypothesized, based on SEM images and considering the low or absent anti-microbial activity on planktonic bacteria showed by flow cytometry. These data suggest that the studied compounds, especially dendrimers, could be considered as novel molecules in the design of research projects aimed at the development of efficacious anti-biofilm disinfection treatments of water systems

  1. Dendrimers and polyamino-phenolic ligands: activity of new molecules against Legionella pneumophila biofilms.

    Directory of Open Access Journals (Sweden)

    Elisa eAndreozzi

    2016-03-01

    Full Text Available Legionnaires’ disease is a potentially fatal pneumonia caused by Legionella pneumophila, an aquatic bacterium often found within the biofilm niche. In man-made water systems microbial biofilms increase the resistance of legionella to disinfection, posing a significant threat to public health. Disinfection methods currently used in water systems have been shown to be ineffective against legionella over the long-term, allowing recolonization by the biofilm-protected microorganisms. In this study, the anti-biofilm activity of previously fabricated polyamino-phenolic ligands and polyamidoamine dendrimers was investigated against legionella mono-species and multi-species biofilms formed by L. pneumophila in association with other bacteria that can be found in tap water (Aeromonas hydrophila, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae. Bacterial ability to form biofilms was verified using a crystal violet colorimetric assay and testing cell viability by real-time quantitative PCR and Plate Count assay. The concentration of the chemicals tested as anti-biofilm agents was chosen based on cytotoxicity assays: the highest non-cytotoxic chemical concentration was used for biofilm inhibition assays, with dendrimer concentration ten-fold higher than polyamino-phenolic ligands. While Macrophen and Double Macrophen were the most active substances among polyamino-phenolic ligands, dendrimers were overall two-fold more effective than all other compounds with a reduction up to 85% and 73% of legionella and multi-species biofilms, respectively. Chemical interaction with matrix molecules is hypothesized, based on SEM images and considering the low or absent anti-microbial activity on planktonic bacteria showed by flow cytometry. These data suggest that the studied compounds, especially dendrimers, could be considered as novel molecules in the design of research projects aimed at the development of efficacious anti-biofilm disinfection

  2. Dendrimers and Polyamino-Phenolic Ligands: Activity of New Molecules Against Legionella pneumophila Biofilms.

    Science.gov (United States)

    Andreozzi, Elisa; Barbieri, Federica; Ottaviani, Maria F; Giorgi, Luca; Bruscolini, Francesca; Manti, Anita; Battistelli, Michela; Sabatini, Luigia; Pianetti, Anna

    2016-01-01

    Legionnaires' disease is a potentially fatal pneumonia caused by Legionella pneumophila, an aquatic bacterium often found within the biofilm niche. In man-made water systems microbial biofilms increase the resistance of legionella to disinfection, posing a significant threat to public health. Disinfection methods currently used in water systems have been shown to be ineffective against legionella over the long-term, allowing recolonization by the biofilm-protected microorganisms. In this study, the anti-biofilm activity of previously fabricated polyamino-phenolic ligands and polyamidoamine dendrimers was investigated against legionella mono-species and multi-species biofilms formed by L. pneumophila in association with other bacteria that can be found in tap water (Aeromonas hydrophila, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae). Bacterial ability to form biofilms was verified using a crystal violet colorimetric assay and testing cell viability by real-time quantitative PCR and Plate Count assay. The concentration of the chemicals tested as anti-biofilm agents was chosen based on cytotoxicity assays: the highest non-cytotoxic chemical concentration was used for biofilm inhibition assays, with dendrimer concentration 10-fold higher than polyamino-phenolic ligands. While Macrophen and Double Macrophen were the most active substances among polyamino-phenolic ligands, dendrimers were overall twofold more effective than all other compounds with a reduction up to 85 and 73% of legionella and multi-species biofilms, respectively. Chemical interaction with matrix molecules is hypothesized, based on SEM images and considering the low or absent anti-microbial activity on planktonic bacteria showed by flow cytometry. These data suggest that the studied compounds, especially dendrimers, could be considered as novel molecules in the design of research projects aimed at the development of efficacious anti-biofilm disinfection treatments of water systems in

  3. Cell uptake mechanisms of PAMAM G4-FITC dendrimer in human myometrial cells

    Energy Technology Data Exchange (ETDEWEB)

    Oddone, Natalia; Zambrana, Ana I.; Tassano, Marcos [Instituto de Investigaciones Biologicas Clemente Estable, Laboratorio de Senalizacion Celular y Nanobiologia (Uruguay); Porcal, Williams [Universidad de la Republica, Grupo de Quimica Medicinal, Instituto de Quimica Biologica, Facultad de Ciencias-Facultad de Quimica (Uruguay); Cabral, Pablo [Universidad de la Republica, Laboratorio de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias (Uruguay); Benech, Juan C., E-mail: benech@iibce.edu.uy [Instituto de Investigaciones Biologicas Clemente Estable, Laboratorio de Senalizacion Celular y Nanobiologia (Uruguay)

    2013-07-15

    The high incidence and severity of diseases which involve smooth muscle dysfunction dictates the need of continued search for novel therapeutic strategies to treat these conditions. Dendrimers are branched macromolecules with multiple end-groups that can be functionalized for applications which include drug delivery. There is no data regarding the cellular uptake mechanisms used by dendrimers in smooth muscle human myometrial cells (HMC). Polyamidoamine G4 dendrimers were conjugated with fluorescein isothiocyanate (FITC) and the resulting conjugate (G4-FITC) was characterized using high-performance liquid chromatography, nuclear magnetic resonance, and atomic force microscopy. G4-FITC showed to have no significant effect on the primary culture HMC viability up to 48 h. HMC incubated with G4-FITC were analyzed by laser confocal microscopy. Peri-nuclear fluorescence distribution was observed at 5 h of incubation or more (24, 36, and 48 h). At 24 h, G4-FITC partially co-localized with lysotracker. Uptake of G4-FITC by HMC was slightly inhibited by filipin (8.0 {+-} 3.9 %) and significantly inhibited by chlorpromazine (63.5 {+-} 3.7 %). In non-electroporated HMC, G4-FITC was never observed inside the cell nucleus. Interestingly, we detected G4-FITC inside the nuclear domain of some electroporated cells. Thus, electroporation changed intracellular G4-FITC localization. Isolated nuclei of HMC incubated with G4-FITC showed fluorescence signal inside the nuclear domain. The results suggest that in HMC, G4-FITC is taken up by clathrin-mediated endocytosis with endosomal and lysosomal localization at 24 h. The combination of electroporation and dendrimers could be an interesting technology to electrotransfer drugs into smooth muscle cells cytosol and nuclei.

  4. Polyester Dendrimers: Smart Carriers for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Jean–d’Amour K. Twibanire

    2014-01-01

    Full Text Available Polyester dendrimers have been shown to be outstanding candidates for biomedical applications. Compared to traditional polymeric drug vehicles, these biodegradable dendrimers show excellent advantages especially as drug delivery systems because they are non-toxic. Here, advances on polyester dendrimers as smart carriers for drug delivery applications have been surveyed. Both covalent and non-covalent incorporation of drugs are discussed.

  5. Polyester Dendrimers: Smart Carriers for Drug Delivery

    OpenAIRE

    Jean–d’Amour K. Twibanire; T. Bruce Grindley

    2014-01-01

    Polyester dendrimers have been shown to be outstanding candidates for biomedical applications. Compared to traditional polymeric drug vehicles, these biodegradable dendrimers show excellent advantages especially as drug delivery systems because they are non-toxic. Here, advances on polyester dendrimers as smart carriers for drug delivery applications have been surveyed. Both covalent and non-covalent incorporation of drugs are discussed.

  6. Dendrimer a versatile polymer in drug delivery

    Directory of Open Access Journals (Sweden)

    Singh Shakti

    2009-01-01

    Full Text Available Dendrimers are a unique class of synthetic macromolecules having highly branched, three-dimensional, nanoscale architecture with very low polydispersity and high functionality. Structural advantages allow dendrimers to play an important role in the fields of nanotechnology, pharmaceutical and medicinal chemistry. This review discusses several aspects of dendrimers, including preparation, dendrimer-drug coupling chemistry, structural models of dendrimer-based drug delivery systems, and physicochemical and toxicological properties. Dendrimers have emerged as one of the most interesting themes for researchers as a result of their unique architecture and macromolecular characteristics. Several groups are involved in exploring their potential as versatile carriers in drug delivery. The use of dendrimers in drug delivery has been reviewed extensively. The increasing relevance of the potential of dendrimers in drug delivery emphasizes the need to explore the routes by which they can be administered. The high level of control possible over the architectural design of dendrimers; their size, shape, branching length/density, and their surface functionality clearly distinguish these structures as unique and optimum carriers in those applications. The bioactive agents may be encapsulated into the interior of the dendrimers or chemically attached/physically adsorbed onto the dendrimer surface, with the option of tailoring the carrier to the specific needs of the active material and its therapeutic applications. This review clearly demonstrates the potential of this new fourth major class of polymer architecture and indeed substantiates the high hopes for the future of dendrimers.

  7. Electrochemical sensor for nitric oxide using layered films composed of a polycationic dendrimer and nickel(II) phthalocyaninetetrasulfonate deposited on a carbon fiber electrode

    International Nuclear Information System (INIS)

    We have developed an electrochemical sensor for nitric oxide that is based on multi-layers of nickel(II) phthalocyaninetetrasulfonate and a polyamidoamine dendrimer assembled on the surface of a carbon-fiber microelectrode. This sensor responds to nitric oxide at a working potential of 800 mV with a sensitivity of 5.54 pA∙μM-1 which, however, depends on the dendrimer layer position deposited on the microelectrode. The limit of detection is as low as 5.5 μM at a signal-to-noise ratio of 3. The electrode exhibits good selectivity for nitric oxide over common interferents including dopamine, nitrite, hydrogen peroxide, norepinephrine, epinephrine and ascorbic acid. (author)

  8. Dendrimers and their Applications: A Review Article

    Directory of Open Access Journals (Sweden)

    Mughisa Munir

    2016-01-01

    Full Text Available Dendrimers are the valuable additives in different routes of drug administration and are the most successful agents, because dendrimers provide greater biocompatibility, water solubility and bioavailability. In this review, synthesis structures, method of preparation have been discussed. Interaction mechanisms between dendrimer molecules and active pharmaceutical ingredient (API, like simple encapsulation and covalent conjugation and the recent applications of dendrimers have also been focused. Divergent method of poly amidoamine (PAMAM dendrimers is found to be more applicable as compare to convergent method and PAMAM are also considered as ideal carriers for drug delivery because of large variety of surface groups, high aqueous solubility, and their unique architecture. 

  9. Ultrasensitive electrochemiluminescent immunoassay for morphine using a gold electrode modified with CdS quantum dots, polyamidoamine, and gold nanoparticles

    International Nuclear Information System (INIS)

    We report on a novel electrochemiluminescent (ECL) immunoassay for the ultrasensitive determination of morphine by making use of a gold electrode which was modified with a nanocomposite film containing self-assembled polyamidoamine (PAMAM) CdS quantum dots and electrodeposited gold nanoparticles (Au-NPs). The highly uniform and well-dispersed quantum dots were capped with PAMAM dendrimers. Due to the synergistic effect of the modified quantum dots and the electrodeposited Au-NPs, the ECL response is dramatically enhanced. Under optimal experimental conditions, the immunoreaction between morphine and anti-morphine antibody resulted in a decrease of the ECL signal because of steric hindrance. The calibration plot is linear in the morphine concentration range from 0.2 to 180 ng•mL−1, with a detection limit as low as 67 pg•mL−1. The sensor was successfully applied to the determination of morphine in blood plasma. This kind of assay is expected to pave new avenues in label-free drug assays. (author)

  10. 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. PMID:27140418

  11. Bioconjugates of PAMAM dendrimers with trans-retinal, pyridoxal, and pyridoxal phosphate

    Directory of Open Access Journals (Sweden)

    Filipowicz A

    2012-09-01

    Full Text Available A Filipowicz, S WołowiecDepartment of Cosmetology, University of Information Technology and Management in Rzeszów, Rzeszów, PolandBackground: Bioconjugates of a polyamidoamine (PAMAM G3 dendrimer and an aldehyde were synthesized as carriers for vitamins A and B6, and the bioavailability of these vitamins for skin nutrition was investigated.Methods: Nuclear magnetic resonance (NMR and ultraviolet-visible methods were used to characterize the structure of the bioconjugates and for monitoring release of pyridoxal (Pyr and pyridoxal phosphate (PLP from these bioconjugates in vitro. A skin model permeation of bioconjugates was also studied in a Franz chamber.Results: A transdermal G3 PAMAM dendrimer was used to synthesize bioconjugates with trans-retinal (Ret, pyridoxal (Pyr, or PLP. These nanomolecules, containing up to four covalently linked Ret, Pyr, or PLP (G34Ret, G34Pyr, and G34PLP, were able to permeate the skin, as demonstrated in vitro using a model skin membrane. PLP and Pyr bound to a macromolecular vehicle were active cofactors for glutamic pyruvic transaminase, as shown by 1H NMR spectral monitoring of the progress of the L-alanine + α-ketoglutarate → glutamic acid + pyruvic acid reaction.Conclusion: PAMAM-PLP, PAMAM-Pyr, and PAMAM-Ret bioconjugates are able to permeate the skin. PLP and Pyr are available as cofactors for glutamic pyruvic transaminase.Keywords: PAMAM, trans-retinal, pyridoxal phosphate, pyridoxal, transamination

  12. Construction and probing of multisite chiral catalysts: dendrimer fixation of c2-symmetrical diphosphinerhodium complexes.

    Science.gov (United States)

    Engel, Gerald D; Gade, Lutz H

    2002-09-16

    A series of chiral phosphine-functionalized poly(propyleneimine) (PPI) dendrimers was synthesized by the reaction of carboxyl-linked C(2)-chiral pyrphos ligand (pyrphos=3,4-bis(diphenylphosphino)pyrrolidine) with zeroth-fourth generation PPI using ethyl-N,N-dimethylaminopropylcarbodiimide (EDC)/1-hydroxybenzotriazol as a coupling reagent. The dendrimers obtained were characterized by NMR spectroscopy and elemental analysis as well as FAB and MALDI-TOF mass spectrometry, which established their molecular masses of up to 20 700 amu. Metalation of the multi-site phosphines with [Rh(COD)(2)]BF(4) cleanly yielded the cationic rhododendrimers containing up to 32 metal centers (for the fourth generation species), representing the largest chiral phosphine dendrimer catalyst studied to date. The complete metalation of the chiral phosphine sites was demonstrated by (31)P NMR spectroscopy and the observation of the coordination-shifted AB part of the ABX spin system (delta(A)=33.9, delta(B)=32.9; (1)J(Rh,P)=150, 153 Hz; (2)J(P,P)=28 Hz). The relationship between the size/generation of the dendrimer and its catalytic properties was established in the asymmetric hydrogenation of Z-methyl-alpha-acetamidocinammate and dimethyl itaconate. A decrease in both activity and selectivity of the dendrimer catalysts was observed on going to the higher generations. PMID:12298024

  13. Glycopeptide dendrimers as Pseudomonas aeruginosa biofilm inhibitors.

    Science.gov (United States)

    Reymond, Jean-Louis; Bergmann, Myriam; Darbre, Tamis

    2013-06-01

    Synthetic glycopeptide dendrimers composed of a branched oligopeptide tree structure appended with glycosidic groups at its multiple N-termini were investigated for binding to the Pseudomonas aeruginosa lectins LecB and LecA. These lectins are partly responsible for the formation of antibiotic resistant biofilms in the human pathogenic bacterium P. aeruginosa, which causes lethal airway infections in immune-compromised and cystic fibrosis patients. Glycopeptide dendrimers with high affinity to the lectins were identified by screening of combinatorial libraries. Several of these dendrimers, in particular the LecB specific glycopeptide dendrimers FD2 and D-FD2 and the LecA specific glycopeptide dendrimers GalAG2 and GalBG2, also efficiently block P. aeruginosa biofilm formation and induce biofilm dispersal in vitro. Structure-activity relationship and structural studies are reviewed, in particular the observation that multivalency is essential to the anti-biofilm effect in these dendrimers.

  14. Conformational sensitivity of conjugated poly(ethylene oxide)-poly(amidoamine) molecules to cations adducted upon electrospray ionization – A mass spectrometry, ion mobility and molecular modeling study

    Energy Technology Data Exchange (ETDEWEB)

    Tintaru, Aura [Aix-Marseille Université – CNRS, UMR 7273, Institut de Chimie Radicalaire, Marseille (France); Chendo, Christophe [Aix-Marseille Université – CNRS, FR 1739, Fédération des Sciences Chimiques de Marseille, Spectropole, Marseille (France); Wang, Qi [Aix-Marseille Université – CNRS, UMR 6114, Centre Interdisciplinaire de Nanosciences de Marseille, Marseille (France); Viel, Stéphane [Aix-Marseille Université – CNRS, UMR 7273, Institut de Chimie Radicalaire, Marseille (France); Quéléver, Gilles; Peng, Ling [Aix-Marseille Université – CNRS, UMR 6114, Centre Interdisciplinaire de Nanosciences de Marseille, Marseille (France); Posocco, Paola [University of Trieste, Molecular Simulation Engineering (MOSE) Laboratory, Department of Engineering and Architecture (DEA), Trieste (Italy); National Interuniversity Consortium for Material Science and Technology (INSTM), Research Unit MOSE-DEA, University of Trieste, Trieste (Italy); Pricl, Sabrina, E-mail: sabrina.pricl@di3.units.it [University of Trieste, Molecular Simulation Engineering (MOSE) Laboratory, Department of Engineering and Architecture (DEA), Trieste (Italy); National Interuniversity Consortium for Material Science and Technology (INSTM), Research Unit MOSE-DEA, University of Trieste, Trieste (Italy); Charles, Laurence, E-mail: laurence.charles@univ-amu.fr [Aix-Marseille Université – CNRS, UMR 7273, Institut de Chimie Radicalaire, Marseille (France)

    2014-01-15

    Graphical abstract: -- Highlights: •ESI-MS/MS, IMS and molecular modeling were combined to study PEO-PAMAM conformation. •Protonated and lithiated molecules were studied, with charge states from 2 to 4. •Protonation mostly occurred on PAMAM, with PEO units enclosing the protonated group. •Lithium adduction on PEO units lead to more expanded conformations. •Charge location strongly influenced PEO-PAMAM dissociation behavior. -- Abstract: Tandem mass spectrometry and ion mobility spectrometry experiments were performed on multiply charged molecules formed upon conjugation of a poly(amidoamine) (PAMAM) dendrimer with a poly(ethylene oxide) (PEO) linear polymer to evidence any conformational modification as a function of their charge state (2+ to 4+) and of the adducted cation (H{sup +}vs Li{sup +}). Experimental findings were rationalized by molecular dynamics simulations. The G0 PAMAM head-group could accommodate up to three protons, with protonated terminal amine group enclosed in a pseudo 18-crown-6 ring formed by the PEO segment. This particular conformation enabled a hydrogen bond network which allowed long-range proton transfer to occur during collisionally activated dissociation. In contrast, lithium adduction was found to mainly occur onto oxygen atoms of the polyether, each Li{sup +} cation being coordinated by a 12-crown-4 pseudo structure. As a result, for the studied polymeric segment (M{sub n} = 1500 g mol{sup −1}), PEO-PAMAM hybrid molecules exhibited a more expanded shape when adducted to lithium as compared to proton.

  15. A Novel Inorganic-Organic Composite Constructed from Cobalt(Ⅱ)-Monosubstituted Polyoxometalates and Poly(amidoamine)-NH2 Dendrimers

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xiao-Feng; LIN Shen; LUO Geng-Geng; LIU Chun-Lian

    2007-01-01

    An inorganic-organic composite was prepared by poly(amidoamine) (PAMAM) dendrimer reacting with cobalt(Ⅱ)-monosubstituted polyoxometalates Na5Co11(H2O)PW11O39 (PW11Co) in an aqueous solution. The hybrid composite PW11Co/PAMAM was characterized by FT-IR, UV-Vis diffuse reflectance spectra (DR-UV-Vis), XPS,XRD and TG/DTA, indicating that the PW11 Co was chemically anchored to PAMAM. The morphologies of the title composite were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The catalytic activity was evaluated by oxidation of isobutyraldehyde (IBA) to isobutyric acid (IBAc) in MeCN under mild conditions (20℃, ambient pressure), showing that the title compound is a more effective and recoverable catalyst than corresponding PW11 Co.

  16. Redox-controlled interaction of biferrocenyl-terminated dendrimers with beta-cyclodextrin molecular printboards.

    Science.gov (United States)

    Nijhuis, Christian A; Dolatowska, Karolina A; Ravoo, Bart Jan; Huskens, Jurriaan; Reinhoudt, David N

    2007-01-01

    This paper describes the synthesis and electrochemistry of biferrocenyl-terminated dendrimers and their beta-cyclodextrin (beta-CD) inclusion complexes in aqueous solution and at surfaces. Three generations of poly(propylene imine) (PPI) dendrimers, decorated with 4, 8, and 16 biferrocenyl (BFc) units, respectively, were synthesized. A water-soluble BFc derivative forms stable inclusion complexes with beta-CD. The intrinsic binding constant is K(i)=2.5 x 10(4) M(-1). The BFc dendrimers were solubilized in water by complexation of the end groups with beta-CD, resulting in large water-soluble supramolecular assemblies. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) showed that all the end groups are complexed to beta-CD. Adsorption of the dendrimers at self-assembled monolayers (SAMs) of heptathioether-functionalized beta-CD on gold ("molecular printboards") resulted in stable monolayers of the dendrimers due to the formation of multivalent host-guest interactions between the BFc end groups of the dendrimers and the immobilized beta-CD molecules. The number of interacting end groups is 3, 4, and 4 for dendrimer generations 1, 2, and 3, respectively. The complexation of BFc to beta-CD is sensitive to the oxidation state of the BFc unit. Oxidation of neutral BFc-Fe(2) ((II,II)) to the cationic, mixed-valence biferrocenium BFc-Fe(2) ((II,III)+) resulted in dissociation of the host-guest complexes. Scan-rate-dependent CV and DPV analyses of the dendrimer-beta-CD assemblies immobilized at the beta-CD host surface and in solution revealed that the dendrimers are oxidized in three steps. First, the surface-beta-CD-bound BFc moieties are oxidized to the mixed-valence state, Fe(2) ((II,III)+), followed by the oxidation of the non-surface-interacting BFc groups to the Fe(2) ((II,III)+) state. The third step involves the oxidation of all the BFc moieties to the Fe(2) ((III,III)2+) state.

  17. Physicochemical and biological properties of self-assembled antisense/poly(amidoamine dendrimer nanoparticles: the effect of dendrimer generation and charge ratio

    Directory of Open Access Journals (Sweden)

    Alireza Nomani

    2010-05-01

    Full Text Available Alireza Nomani1,6, Ismaeil Haririan1,5, Ramin Rahimnia2,4, Shamileh Fouladdel2, Tarane Gazori1, Rassoul Dinarvand1, Yadollah Omidi3, Ebrahim Azizi2,41Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 2Molecular Research Lab, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 3Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; 4Department of Medical Biotechnology, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran; 5Biomaterials Research Center (BRC Tehran, Iran; 6Department of Pharmaceutics, Faculty of Pharmacy, Zanjan University of Medical Sciences, Zanjan, IranAbstract: 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 molecules produce more heterodisperse and large nanoparticles when they are condensed with a cationic dendrimer. AFM images also showed that such nanoparticles were spherical. The stability of the antisense content of the nanoparticles was investigated over different charge ratios using polyacrylamide gel electrophoresis. It was clear from such analyses that much more than charge neutrality point was required to obtain stable nanoparticles. For cell uptake, self-assembled nanoparticles were prepared with PAMAM G5 and 5’-FITC labeled antisense and the uptake experiment was carried out in T47D cell culture. This investigation also shows that the cytotoxicity of the nanoparticles was

  18. (99m)Tc-Labeled Multifunctional Low-Generation Dendrimer-Entrapped Gold Nanoparticles for Targeted SPECT/CT Dual-Mode Imaging of Tumors.

    Science.gov (United States)

    Li, Xin; Xiong, Zuogang; Xu, Xiaoying; Luo, Yu; Peng, Chen; Shen, Mingwu; Shi, Xiangyang

    2016-08-10

    Development of cost-effective and highly efficient nanoprobes for targeted tumor single-photon emission computed tomography (SPECT)/computed tomography (CT) dual-mode imaging remains a challenging task. Here, multifunctional dendrimer-entrapped gold nanoparticles (Au DENPs) modified with folic acid (FA) and labeled with (99m)Tc were synthesized for targeted dual-mode SPECT/CT imaging of tumors. Generation 2 (G2) poly(amidoamine) (PAMAM) dendrimers (G2-NH2) conjugated with cyclic diethylenetriamine pentaacetic anhydride (cDTPAA) via an amide linkage and FA via a spacer of polyethylene glycol (PEG) were used for templated synthesis of Au core NPs, followed by labeling of (99m)Tc via chelation. The thus created multifunctional Au DENPs were well-characterized. It is shown that particles with an average Au core diameter of 1.6 nm can be dispersed in water, display stability under different conditions, and are cytocompatible in the studied concentration range. Further results demonstrate that the multifunctional nanoprobe is able to be utilized for targeted SPECT/CT dual-mode imaging of cancer cells having FA receptor (FAR)-overexpression in vitro and the established subcutaneous tumor model in vivo within a time frame up to 4 h. The formed multifunctional Au DENPs synthesized using dendrimers of low-generation may be employed as an effective and economic nanoprobe for SPECT/CT imaging of different types of FAR-expressing tumors. PMID:27434031

  19. Sandwich-format electrochemiluminescence assays for tumor marker based on PAMAM dendrimer-L-cysteine-hollow gold nanosphere nanocomposites.

    Science.gov (United States)

    Zhuo, Ying; Gui, Guofeng; Chai, Yaqin; Liao, Ni; Xiao, Kai; Yuan, Ruo

    2014-03-15

    In this work, a novel polyamidoamine (PAMAM) dendrimer-L-cysteine-hollow gold nanospheres nanocomposite was fabricated and used as the promoter for the peroxydisulfate/O2 ECL system to detect the concentration of the tumor marker carcinoembryonic antigen (CEA). Herein, the carboxyl-terminated PAMAM dendrimers were decorated with L-cysteine (L-Cys) by EDC/NHS coupling chemistry. Then, the hollow gold nanospheres (HGNPs) were employed as effective nano-carriers for the assembly of PAMAM-L-Cys via thiols-Au bonding, which was used for further loading of detection antibody (Ab2) to form the PAMAM-L-Cys-HGNPs-Ab2 bioconjugates. In the presence of target CEA, the sandwiched immuno-structure can be formed between the capture anti-CEA antibodies (Ab1), which self-assembled on deposited gold modified electrode, and the Ab2 on the PAMAM-L-Cys-HGNPs, thereby resulting in a proportional increase in ECL response, due to the significant enhancement of PAMAM-L-Cys-HGNPs toward peroxydisulfate/O2 ECL system. As a result, a sandwich ECL assay for CEA detection was developed with excellent sensitivity of a large concentration variation from 20 fg/mL to 1.0 ng/mL and a detection limit of 6.7 fg mL(-1). PMID:24211458

  20. Graphene Dendrimer-stabilized silver nanoparticles for detection of methimazole using Surface-enhanced Raman scattering with computational assignment

    Science.gov (United States)

    Saleh, Tawfik A.; Al-Shalalfeh, Mutasem M.; Al-Saadi, Abdulaziz A.

    2016-01-01

    Graphene functionalized with polyamidoamine dendrimer, decorated with silver nanoparticles (G-D-Ag), was synthesized and evaluated as a substrate with surface-enhanced Raman scattering (SERS) for methimazole (MTZ) detection. Sodium borohydride was used as a reducing agent to cultivate silver nanoparticles on the dendrimer. The obtained G-D-Ag was characterized by using UV-vis spectroscopy, scanning electron microscope (SEM), high-resolution transmission electron microscope (TEM), Fourier-transformed infrared (FT-IR) and Raman spectroscopy. The SEM image indicated the successful formation of the G-D-Ag. The behavior of MTZ on the G-D-Ag as a reliable and robust substrate was investigated by SERS, which indicated mostly a chemical interaction between G-D-Ag and MTZ. The bands of the MTZ normal spectra at 1538, 1463, 1342, 1278, 1156, 1092, 1016, 600, 525 and 410 cm−1 were enhanced due to the SERS effect. Correlations between the logarithmical scale of MTZ concentrations and SERS signal intensities were established, and a low detection limit of 1.43 × 10−12 M was successfully obtained. The density functional theory (DFT) approach was utilized to provide reliable assignment of the key Raman bands. PMID:27572919

  1. Graphene Dendrimer-stabilized silver nanoparticles for detection of methimazole using Surface-enhanced Raman scattering with computational assignment.

    Science.gov (United States)

    Saleh, Tawfik A; Al-Shalalfeh, Mutasem M; Al-Saadi, Abdulaziz A

    2016-01-01

    Graphene functionalized with polyamidoamine dendrimer, decorated with silver nanoparticles (G-D-Ag), was synthesized and evaluated as a substrate with surface-enhanced Raman scattering (SERS) for methimazole (MTZ) detection. Sodium borohydride was used as a reducing agent to cultivate silver nanoparticles on the dendrimer. The obtained G-D-Ag was characterized by using UV-vis spectroscopy, scanning electron microscope (SEM), high-resolution transmission electron microscope (TEM), Fourier-transformed infrared (FT-IR) and Raman spectroscopy. The SEM image indicated the successful formation of the G-D-Ag. The behavior of MTZ on the G-D-Ag as a reliable and robust substrate was investigated by SERS, which indicated mostly a chemical interaction between G-D-Ag and MTZ. The bands of the MTZ normal spectra at 1538, 1463, 1342, 1278, 1156, 1092, 1016, 600, 525 and 410 cm(-1) were enhanced due to the SERS effect. Correlations between the logarithmical scale of MTZ concentrations and SERS signal intensities were established, and a low detection limit of 1.43 × 10(-12) M was successfully obtained. The density functional theory (DFT) approach was utilized to provide reliable assignment of the key Raman bands. PMID:27572919

  2. Electrochemical characterization of methanol/O2 biofuel cell: Use of laccase biocathode immobilized with polypyrrole film and PAMAM dendrimers

    International Nuclear Information System (INIS)

    This paper describes the performance of a mediated electron transfer (MET) biocathode for a methanol/O2 biofuel cell. To this end, we employed PAMAM (polyamidoamine) dendrimers for the immobilization of laccase using 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) diammonium salt (ABTS) in solution or entrapped into polypyrrole films. We used the enzyme immobilized onto the carbon platform obtained either in the presence or in the absence of the electropolymerized film to determine kinetic parameters. The results point to a very similar kinetic rate conversion in both situations; however, substrate affinity seems to increase in the bioelectrode containing the entrapped substrate molecules. The electrochemical characterization tests confirmed that the electropolymerized polypyrrole film was able to retain entrapped ABTS molecules. Additionally, laccase provides enhanced catalytic oxidation current for the mediator compared with the control sample containing PAMAM dendrimer only. Compared to the control sample, which gave power density values around 0.7 μW cm−2, tests employing ABTS as mediator furnished 6 μW cm−2 when the mediator was added in solution and around 25 μW cm−2 when it was entrapped into the biocathode layers. Overall, the developed biocathode is environmentally friendly for immobilization of the enzyme laccase, being satisfactorily stable in the kinetic tests and affording good power data in the biofuel cell tests

  3. Graphene Dendrimer-stabilized silver nanoparticles for detection of methimazole using Surface-enhanced Raman scattering with computational assignment

    Science.gov (United States)

    Saleh, Tawfik A.; Al-Shalalfeh, Mutasem M.; Al-Saadi, Abdulaziz A.

    2016-08-01

    Graphene functionalized with polyamidoamine dendrimer, decorated with silver nanoparticles (G-D-Ag), was synthesized and evaluated as a substrate with surface-enhanced Raman scattering (SERS) for methimazole (MTZ) detection. Sodium borohydride was used as a reducing agent to cultivate silver nanoparticles on the dendrimer. The obtained G-D-Ag was characterized by using UV-vis spectroscopy, scanning electron microscope (SEM), high-resolution transmission electron microscope (TEM), Fourier-transformed infrared (FT-IR) and Raman spectroscopy. The SEM image indicated the successful formation of the G-D-Ag. The behavior of MTZ on the G-D-Ag as a reliable and robust substrate was investigated by SERS, which indicated mostly a chemical interaction between G-D-Ag and MTZ. The bands of the MTZ normal spectra at 1538, 1463, 1342, 1278, 1156, 1092, 1016, 600, 525 and 410 cm‑1 were enhanced due to the SERS effect. Correlations between the logarithmical scale of MTZ concentrations and SERS signal intensities were established, and a low detection limit of 1.43 × 10‑12 M was successfully obtained. The density functional theory (DFT) approach was utilized to provide reliable assignment of the key Raman bands.

  4. Graphene Dendrimer-stabilized silver nanoparticles for detection of methimazole using Surface-enhanced Raman scattering with computational assignment

    Science.gov (United States)

    Saleh, Tawfik A.; Al-Shalalfeh, Mutasem M.; Al-Saadi, Abdulaziz A.

    2016-08-01

    Graphene functionalized with polyamidoamine dendrimer, decorated with silver nanoparticles (G-D-Ag), was synthesized and evaluated as a substrate with surface-enhanced Raman scattering (SERS) for methimazole (MTZ) detection. Sodium borohydride was used as a reducing agent to cultivate silver nanoparticles on the dendrimer. The obtained G-D-Ag was characterized by using UV-vis spectroscopy, scanning electron microscope (SEM), high-resolution transmission electron microscope (TEM), Fourier-transformed infrared (FT-IR) and Raman spectroscopy. The SEM image indicated the successful formation of the G-D-Ag. The behavior of MTZ on the G-D-Ag as a reliable and robust substrate was investigated by SERS, which indicated mostly a chemical interaction between G-D-Ag and MTZ. The bands of the MTZ normal spectra at 1538, 1463, 1342, 1278, 1156, 1092, 1016, 600, 525 and 410 cm-1 were enhanced due to the SERS effect. Correlations between the logarithmical scale of MTZ concentrations and SERS signal intensities were established, and a low detection limit of 1.43 × 10-12 M was successfully obtained. The density functional theory (DFT) approach was utilized to provide reliable assignment of the key Raman bands.

  5. A novel dendrimer based on poly (L-glutamic acid) derivatives as an efficient and biocompatible gene delivery vector

    Science.gov (United States)

    Zeng, Xin; Pan, Shirong; Li, Jie; Wang, Chi; Wen, Yuting; Wu, Hongmei; Wang, Cuifeng; Wu, Chuanbin; Feng, Min

    2011-09-01

    Non-viral gene delivery systems based on cationic polymers have faced limitations related to their relative low gene transfer efficiency, cytotoxicity and system instability in vivo. In this paper, a flexible and pompon-like dendrimer composed of poly (amidoamine) (PAMAM) G4.0 as the inner core and poly (L-glutamic acid) grafted low-molecular-weight polyethylenimine (PLGE) as the surrounding multiple arms was synthesized (MGI dendrimer). The novel MGI dendrimer was designed to combine the merits of size-controlled PAMAM G4.0 and the low toxicity and flexible chains of PLGE. In phosphate-buffered saline dispersions the well-defined DNA/MGI complex above a N/P ratio of 30 showed good stability with particle sizes of approximately 200 nm and a comparatively low polydispersity index. However, the particle size of the DNA/25 kDa polyethylenimine (DNA/PEI 25K) complex was larger than 700 nm under the same salt conditions. The shielding of the compact amino groups at the periphery of flexible PAMAM and biocompatible PLGE chains in MGI resulted in a dramatic decrease of the cytotoxicity compared to native PAMAM G4.0 dendrimer. The in vitro transfection efficiency of DNA/MGI dendrimer complex was higher than that of PAMAM G4.0 dendrimer. Importantly, in serum-containing medium, DNA/MGI complexes at their optimal N/P ratio maintained the same high levels of transfection efficiency as in serum-free medium, while the transfection efficiency of native PAMAM G4.0, PEI 25K and Lipofectamine 2000 were sharply decreased. In vivo gene delivery of pVEGF165/MGI complex into balloon-injured rabbit carotid arteries resulted in significant inhibition of restenosis by increasing VEGF165 expression in local vessels. Therefore, the pompon-like MGI dendrimer may be a promising vector candidate for efficient gene delivery in vivo.

  6. The Olefin Metathesis Reactions in Dendrimers

    Science.gov (United States)

    Astruc, Didier

    Dendrimers containing terminal olefins or ruthenium-benzylidene terminal groups undergo olefin metathesis reactions (RCM and ROMP types), and essentially results from our group are reviewed here. Dendrimers have been loaded at their periphery with ruthenium-chelating bis-phosphines, which leads to the formation of dendrimer-cored stars by ring-opening-metathesis polymerization (ROMP). CpFe+-induced perallylation of polymethylaromatics (Cp = η5-C5H5) followed by ring-closing metathesis (RCM) and/or cross metathesis (CM) leads to poly-ring, cage, oligomeric and polymeric architectures. In the presence of acrylic acid or metha-crylate, stereospecific CM inhibits oligomerization, and dendritic olefins yield polyacid dendrimers. Finally, cros-metahesis reactions with dendronic acrylate allow dendritic construction and growth.

  7. Antinematic local order in dendrimer liquids

    OpenAIRE

    Georgiou, Ioannis A.; Ziherl, Primož; Kahl, Gerhard

    2013-01-01

    We use monomer-resolved numerical simulations to study the positional and orientational structure of a dense dendrimer solution, focusing on the effects of dendrimers' prolate shape and deformability on the short-range order. Our results provide unambiguous evidence that the nearest-neighbor shell of a tagged particle consists of a mixture of crossed, side-by-side, side-to-end, and end-to-end pair configurations, imposing antinematic rather than nematic order observed in undeformable rodlike ...

  8. Smart dendrimer-based nanogel for enhancing 5-fluorouracil loading efficiency against MCF7 cancer cell growth

    Indian Academy of Sciences (India)

    PHUNG NGAN LE; NGOC HOA NGUYEN; CUU KHOA NGUYEN; NGOC QUYEN TRAN

    2016-10-01

    Nano-carriers are not only evaluated as a novel kind of drug delivery, but also expected to bypass the critical bottleneck of conventional cancer chemotherapeutics. Among them, thermo-sensitive nanogel draws muchattention due to its efficacy in the loading and release of hydrophobic drugs. In the study, we developed a promising thermosensitive polymer-grafted dendrimer to enhance drug-loading efficiency, which was prepared from conjugationof thermo-sensitive carboxylic-terminated poly(N-isopropylacrylamide) polymer (PNIPAM) with polyamidoamine (PAMAM) dendrimer (G3.0). The obtained copolymer structure and molecular weight were confirmed by proton nuclear magnetic resonance (${}^!$H NMR) and gel permeation chromatography (GPC), respectively. Morphology of the nanocarrier was observed around 120–150 nm by transmission electron microscopy (TEM) and 200 nm by dynamic light scattering (DLS). The nanocarrier exhibited the higher drug loading (DL = 7.79%) and entrapment efficiency (EE = 42.25%) of 5-FU compared to PAMAM dendrimer G3.0 (DL = 2.25% and EE = 11.52%). In-vitro test, the 5-FU-loaded in PAMAM G3.0–PNIPAM could release approximately 40% of the encapsulated drug at pH = 7.4 after 5 days tracking, while the cumulative anticancer drugs achieved nearly two-fold increase (around 75%)at pH 5.5 during the same time.Moreover, the cytotoxicity assay results also indicated that the drug-loaded nanocarrier exhibited a significant growth inhibition of the MCF-7 cancer cell. The obtained resulted possibly offered agreat potential of the nanocarrier which may be utilized in delivering other anticancer drugs or dual drugs for chemotherapy in future.

  9. Multifunctional dendrimer-based nanoparticles for in vivo MR/CT dual-modal molecular imaging of breast cancer

    Directory of Open Access Journals (Sweden)

    Li K

    2013-07-01

    Full Text Available Kangan Li,1,4,5,* Shihui Wen,2,* Andrew C Larson,4,5 Mingwu Shen,2 Zhuoli Zhang,4,5 Qian Chen,3 Xiangyang Shi,2,3 Guixiang Zhang1 1Department of Radiology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, People’s Republic of China; 3State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai, People’s Republic of China; 4Departments of Radiology and Biomedical Engineering, Northwestern University, Chicago, IL, USA; 5Robert H Lurie Comprehensive Cancer Center, Chicago, IL, USA *These authors contributed equally to this work Abstract: Development of dual-mode or multi-mode imaging contrast agents is important for accurate and self-confirmatory diagnosis of cancer. We report a new multifunctional, dendrimer-based gold nanoparticle (AuNP as a dual-modality contrast agent for magnetic resonance (MR/computed tomography (CT imaging of breast cancer cells in vitro and in vivo. In this study, amine-terminated generation 5 poly(amidoamine dendrimers modified with gadolinium chelate (DOTA-NHS and polyethylene glycol monomethyl ether were used as templates to synthesize AuNPs, followed by Gd(III chelation and acetylation of the remaining dendrimer terminal amine groups; multifunctional dendrimer-entrapped AuNPs (Gd-Au DENPs were formed. The formed Gd-Au DENPs were used for both in vitro and in vivo MR/CT imaging of human MCF-7 cancer cells. Both MR and CT images demonstrate that MCF-7 cells and the xenograft tumor model can be effectively imaged. The Gd-Au DENPs uptake, mainly in the cell cytoplasm, was confirmed by transmission electron microscopy. The cell cytotoxicity assay, cell morphology observation, and flow cytometry show that the developed Gd-Au DENPs have good biocompatibility in the given concentration range. Our results

  10. 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.

  11. 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

    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...... 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...... on the dendrimer host. The influence of side-chain motif on interactions with the host is analyzed by using seven different N-Boc-protected tripeptides as guests for the dendrimer, Downfield shifts of up to 1.3 ppm were observed for the guest amide NH-proton signals. These shifts decrease with increasing...

  12. 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.

  13. Oligothia dendrimers for the formation of gold nanoparticles

    NARCIS (Netherlands)

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

    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 po

  14. Tetrahedron DNA dendrimers and their encapsulation of gold nanoparticles.

    Science.gov (United States)

    Zhou, Tao; Wang, Yijie; Dong, Yuanchen; Chen, Chun; Liu, Dongsheng; Yang, Zhongqiang

    2014-08-15

    DNA dendrimers have achieved increasing attention recently. Previously reported DNA dendrimers used Y-DNA as monomers. Tetrahedron DNA is a rigid tetrahedral cage made of DNA. Herein, we use tetrahedron DNA as monomers to prepare tetrahedron DNA dendrimers. The prepared tetrahedron DNA dendrimers have larger size compared with those made of Y-DNA. In addition, thanks to the central cavity of tetrahedron DNA monomers, some nanoscale structures (e.g., gold nanoparticles) can be encapsulated within tetrahedron DNA monomers. Tetrahedron DNA encapsulated with gold nanoparticles can be further assembled into dendrimers, guiding gold nanoparticles into clusters.

  15. Convergent synthesis of dendrimers via the Passerini three-component reaction.

    Science.gov (United States)

    Jee, Jo-Ann; Spagnuolo, Lauren A; Rudick, Jonathan G

    2012-07-01

    Tuning properties by programming the surface functional group composition of surface-block dendrimers has been limited to dendrimers with only two types of surface functionality (i.e., surface-diblock dendrimers). The Passerini reaction provides dendrimer products from precursor dendrons in reasonable yields. This proof-of-principle experiment opens the door to making surface-triblock dendrimers. PMID:22702475

  16. Molecular Dynamics Study of the Structure, Flexibility, and Hydrophilicity of PETIM Dendrimers: A Comparison with PAMAM Dendrimers.

    Science.gov (United States)

    Kanchi, Subbarao; Suresh, Gorle; Priyakumar, U Deva; Ayappa, K G; Maiti, Prabal K

    2015-10-15

    A new class of dendrimers, the poly(propyl ether imine) (PETIM) dendrimer, has been shown to be a novel hyperbranched polymer having potential applications as a drug delivery vehicle. Structure and dynamics of the amine terminated PETIM dendrimer and their changes with respect to the dendrimer generation are poorly understood. Since most drugs are hydrophobic in nature, the extent of hydrophobicity of the dendrimer core is related to its drug encapsulation and retention efficacy. In this study, we carry out fully atomistic molecular dynamics (MD) simulations to characterize the structure of PETIM (G2-G6) dendrimers in salt solution as a function of dendrimer generation at different protonation levels. Structural properties such as radius of gyration (Rg), radial density distribution, aspect ratio, and asphericity are calculated. In order to assess the hydrophilicity of the dendrimer, we compute the number of bound water molecules in the interior of dendrimer as well as the number of dendrimer-water hydrogen bonds. We conclude that PETIM dendrimers have relatively greater hydrophobicity and flexibility when compared with their extensively investigated PAMAM counterparts. Hence PETIM dendrimers are expected to have stronger interactions with lipid membranes as well as improved drug encapsulation and retention properties when compared with PAMAM dendrimers. We compute the root-mean-square fluctuation of dendrimers as well as their entropy to quantify the flexibility of the dendrimer. Finally we note that structural and solvation properties computed using force field parameters derived based on the CHARMM general purpose force field were in good quantitative agreement with those obtained using the generalized Amber force field (GAFF). PMID:26378813

  17. Molecular Dynamics Study of the Structure, Flexibility, and Hydrophilicity of PETIM Dendrimers: A Comparison with PAMAM Dendrimers.

    Science.gov (United States)

    Kanchi, Subbarao; Suresh, Gorle; Priyakumar, U Deva; Ayappa, K G; Maiti, Prabal K

    2015-10-15

    A new class of dendrimers, the poly(propyl ether imine) (PETIM) dendrimer, has been shown to be a novel hyperbranched polymer having potential applications as a drug delivery vehicle. Structure and dynamics of the amine terminated PETIM dendrimer and their changes with respect to the dendrimer generation are poorly understood. Since most drugs are hydrophobic in nature, the extent of hydrophobicity of the dendrimer core is related to its drug encapsulation and retention efficacy. In this study, we carry out fully atomistic molecular dynamics (MD) simulations to characterize the structure of PETIM (G2-G6) dendrimers in salt solution as a function of dendrimer generation at different protonation levels. Structural properties such as radius of gyration (Rg), radial density distribution, aspect ratio, and asphericity are calculated. In order to assess the hydrophilicity of the dendrimer, we compute the number of bound water molecules in the interior of dendrimer as well as the number of dendrimer-water hydrogen bonds. We conclude that PETIM dendrimers have relatively greater hydrophobicity and flexibility when compared with their extensively investigated PAMAM counterparts. Hence PETIM dendrimers are expected to have stronger interactions with lipid membranes as well as improved drug encapsulation and retention properties when compared with PAMAM dendrimers. We compute the root-mean-square fluctuation of dendrimers as well as their entropy to quantify the flexibility of the dendrimer. Finally we note that structural and solvation properties computed using force field parameters derived based on the CHARMM general purpose force field were in good quantitative agreement with those obtained using the generalized Amber force field (GAFF).

  18. 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.

  19. DENDRIMERS: SYNTHESIS, ITS DOSAGE FORMS AND ADVANTAGE OVER LINEAR POLYMERS

    Directory of Open Access Journals (Sweden)

    MANINDER KAUR

    2014-08-01

    Full Text Available Objective: The main objective of this study is to improve existing therapies and find new drugs based on dendrimers. Nanoparticle drug-delivery systems are able to increase the selectivity and stability of therapeutic agents. However reticuloendothelial system (RES uptake, drug leakage, immunogenicity, hemolytic toxicity, cytotoxicity, hydrophobicity restrict the use of these nanostructures. These shortcomings are overcome by surface engineering by the dendrimer such as Polyester dendrimer, Citric acid dendrimer, Arginine dendrimer, Glycodendrimers, PEGylated dendrimers, etc.Conclusion: From this present review study, we concluded that dendrimers can work as a useful tool for optimizing drug delivery of such problematic drugs. Also the problem of biocompatibility and toxicity can be overcome by careful surface engineering.

  20. 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.

  1. Nitric oxide releasing-dendrimers: an overview

    Directory of Open Access Journals (Sweden)

    Antonio Carlos Roveda Júnior

    2013-01-01

    Full Text Available Platforms able to storage, release or scavenge NO in a controlled and specific manner is interesting for biological applications. Among the possible matrices for these purposes, dendrimers are excellent candidates for that. These molecules have been used as drug delivery systems and exhibit interesting properties, like the possibility to perform chemical modifications on dendrimers surface, the capacity of storage high concentrations of compounds of interest in the same molecule and the ability to improve the solubility and the biocompatibility of the compounds bonded to it. This review emphasizes the recent progress in the development and in the biological applications of different NO-releasing dendrimers and the nitric oxide release pathways in these compounds.

  2. Multivalent supramolecular dendrimer-based drugs.

    Science.gov (United States)

    Galeazzi, Simone; Hermans, Thomas M; Paolino, Marco; Anzini, Maurizio; Mennuni, Laura; Giordani, Antonio; Caselli, Gianfranco; Makovec, Francesco; Meijer, E W; Vomero, Salvatore; Cappelli, Andrea

    2010-01-11

    Supramolecular complexes consisting of a hydrophobic dendrimer host [DAB-dendr-(NHCONH-Ad)(64)] as well as solubilizing and bioactive guest molecules have been synthesized using a noncovalent approach. The guest-host supramolecular assembly is first preassembled in chloroform and transferred via the neat phase to aqueous solution. The bioactive guest molecules can bind to a natural (serotonin 5-HT(3)) receptor with nanomolar affinity as well as to the synthetic dendrimer receptor in aqueous solution, going toward a dynamic multivalent supramolecular construct capable of adapting itself to a multimeric receptor motif.

  3. Dendrimer based nanotherapeutics for ocular drug delivery

    Science.gov (United States)

    Kambhampati, Siva Pramodh

    PAMAM dendrimers are a class of well-defined, hyperbranched polymeric nanocarriers that are being investigated for ocular drug and gene delivery. Their favorable properties such as small size, multivalency and water solubility can provide significant opportunities for many biologically unstable drugs and allows potentially favorable ocular biodistribution. This work exploits hydroxyl terminated dendrimers (G4-OH) as drug/gene delivery vehicles that can target retinal microglia and pigment epithelium via systemic delivery with improved efficacy at much lower concentrations without any side effects. Two different drugs Triamcinolone acetonide (TA) and N-Acetyl Cysteine (NAC) conjugated to G4-OH dendrimers showed tailorable sustained release in physiological relevant solutions and were evaluated in-vitro and in-vivo. Dendrimer-TA conjugates enhanced the solubility of TA and were 100 fold more effective at lower concentrations than free TA in its anti-inflammatory activity in activated microglia and in suppressing VEGF production in hypoxic RPE cells. Dendrimers targeted activated microglia/macrophages and RPE and retained for a period of 21 days in I/R mice model. The relative retention of intravitreal and intravenous dendrimers was comparable, if a 30-fold intravenous dose is used; suggesting intravenous route targeting retinal diseases are possible with dendrimers. D-NAC when injected intravenously attenuated retinal and choroidal inflammation, significantly reduced (˜73%) CNV growth at early stage of AMD in rat model of CNV. A combination therapy of D-NAC + D-TA significantly suppressed microglial activation and promoted CNV regression in late stages of AMD without causing side-effects. G4-OH was modified with linker having minimal amine groups and incorporation of TA as a nuclear localization enhancer resulted in compact gene vectors with favorable safety profile and achieved high levels of transgene expression in hard to transfect human retinal pigment

  4. Dendrimers in Layer-by-Layer Assemblies: Synthesis and Applications

    Directory of Open Access Journals (Sweden)

    Katsuhiko Sato

    2013-07-01

    Full Text Available We review the synthesis of dendrimer-containing layer-by-layer (LbL assemblies and their applications, including biosensing, controlled drug release, and bio-imaging. Dendrimers can be built into LbL films and microcapsules by alternating deposition of dendrimers and counter polymers on the surface of flat substrates and colloidal microparticles through electrostatic bonding, hydrogen bonding, covalent bonding, and biological affinity. Dendrimer-containing LbL assemblies have been used to construct biosensors, in which electron transfer mediators and metal nanoparticles are often coupled with dendrimers. Enzymes have been successfully immobilized on the surface of electrochemical and optical transducers by forming enzyme/dendrimer LbL multilayers. In this way, high-performance enzyme sensors are fabricated. In addition, dendrimer LbL films and microcapsules are useful for constructing drug delivery systems because dendrimers bind drugs to form inclusion complexes or the dendrimer surface is covalently modified with drugs. Magnetic resonance imaging of cancer cells by iron oxide nanoparticles coated with dendrimer LbL film is also discussed.

  5. Selective aggregation of PAMAM dendrimer nanocarriers and PAMAM/ZnPc nanodrugs on human atheromatous carotid tissues: a photodynamic therapy for atherosclerosis

    Science.gov (United States)

    Spyropoulos-Antonakakis, Nikolaos; Sarantopoulou, Evangelia; Trohopoulos, Panagiotis N.; Stefi, Aikaterina L.; Kollia, Zoe; Gavriil, Vassilios E.; Bourkoula, Athanasia; Petrou, Panagiota S.; Kakabakos, Sotirios; Semashko, Vadim V.; Nizamutdinov, Alexey S.; Cefalas, Alkiviadis-Constantinos

    2015-05-01

    Photodynamic therapy (PDT) involves the action of photons on photosensitive molecules, where atomic oxygen or OH- molecular species are locally released on pathogenic human cells, which are mainly carcinogenic, thus causing cell necrosis. The efficacy of PDT depends on the local nanothermodynamic conditions near the cell/nanodrug system that control both the level of intracellular translocation of nanoparticles in the pathogenic cell and their agglomeration on the cell membrane. Dendrimers are considered one of the most effective and promising drug carriers because of their relatively low toxicity and negligible activation of complementary reactions. Polyamidoamine (PAMAM) dendrite delivery of PDT agents has been investigated in the last few years for tumour selectivity, retention, pharmacokinetics and water solubility. Nevertheless, their use as drug carriers of photosensitizing molecules in PDT for cardiovascular disease, targeting the selective necrosis of macrophage cells responsible for atheromatous plaque growth, has never been investigated. Furthermore, the level of aggregation, translocation and nanodrug delivery efficacy of PAMAM dendrimers or PAMAM/zinc phthalocyanine (ZnPc) conjugates on human atheromatous tissue and endothelial cells is still unknown.

  6. Influence of PAMAM dendrimers on the human insulin

    Science.gov (United States)

    Nowacka, Olga; Miłowska, Katarzyna; Ionov, Maksim; Bryszewska, Maria

    2015-12-01

    Dendrimers are specific class of polymeric macromolecules with wide spectrum of properties. One of the promising activities of dendrimers involves inhibition of protein fibril formation. Aggregation and fibrillation of insulin occurs in insulin-dependent diabetic patients after repeated administration, due to these processes being very easily triggered by the conditions of drug administration. The aim of this work was to study the influence of various generations PAMAM dendrimers on human insulin zeta potential, secondary structure and dithiotreitol (DTT)-induced aggregation. We observed the dependence between the number of positive charges on the surface of the PAMAM dendrimer and the values of zeta potential. Addition of dendrimers to insulin caused insignificant changes in the secondary structure. There was a small decrease in ellipticity, but it did not result in alterations in the circular dichroism (CD) spectrum shape. Dendrimers neither induced protein aggregation nor inhibited the aggregation process induced by DTT, except for 0.01 µmol/l concentration.

  7. Azide Tripodal Dendrons from Behera's Amine and Their Clicked Dendrimers.

    Science.gov (United States)

    Barmare, Farhana; Abadjian, Marie-Caline Z; Wiener, Erik C; Grotjahn, Douglas B

    2016-08-01

    Diazo transfer reactions on Behera's amine and its next-generation analogue formed G0 and G1 azide dendrons bearing three and nine tert-butyl-protected esters, respectively. The utility of the new dendrons was demonstrated by copper-catalyzed azide-alkyne cycloaddition, with 1,3,5-triethynylbenzene, forming two novel dendrimers in a convergent manner. Acid-mediated dendrimer deprotection was successful, and the resulting carboxy-terminated dendrimers were analyzed by NMR and DOSY experiments. PMID:27454340

  8. Synthesis and Spectral Studies of CdTe–Dendrimer Conjugates

    OpenAIRE

    Ghosh Srabanti; Saha Abhijit

    2009-01-01

    Abstract In order to couple high cellular uptake and target specificity of dendrimer molecule with excellent optical properties of semiconductor nanoparticles, the interaction of cysteine-capped CdTe quantum dots with dendrimer was investigated through spectroscopic techniques. NH2-terminated dendrimer molecule quenched the photoluminescence of CdTe quantum dots. The binding constants and binding capacity were calculated, and the nature of binding was found to be noncovalent. Significant decr...

  9. Mixed Matrix PVDF Membranes With in Situ Synthesized PAMAM Dendrimer-Like Particles: A New Class of Sorbents for Cu(II) Recovery from Aqueous Solutions by Ultrafiltration.

    Science.gov (United States)

    Kotte, Madhusudhana Rao; Kuvarega, Alex T; Cho, Manki; Mamba, Bhekie B; Diallo, Mamadou S

    2015-08-18

    Advances in industrial ecology, desalination, and resource recovery have established that industrial wastewater, seawater, and brines are important and largely untapped sources of critical metals and elements. A Grand Challenge in metal recovery from industrial wastewater is to design and synthesize high capacity, recyclable and robust chelating ligands with tunable metal ion selectivity that can be efficiently processed into low-energy separation materials and modules. In our efforts to develop high capacity chelating membranes for metal recovery from impaired water, we report a one-pot method for the preparation of a new family of mixed matrix polyvinylidene fluoride (PVDF) membranes with in situ synthesized poly(amidoamine) [PAMAM] particles. The key feature of our new membrane preparation method is the in situ synthesis of PAMAM dendrimer-like particles in the dope solutions prior to membrane casting using low-generation dendrimers (G0 and G1-NH2) with terminal primary amine groups as precursors and epichlorohydrin (ECH) as cross-linker. By using a combined thermally induced phase separation (TIPS) and nonsolvent induced phase separation (NIPS) casting process, we successfully prepared a new family of asymmetric PVDF ultrafiltration membranes with (i) neutral and hydrophilic surface layers of average pore diameters of 22-45 nm, (ii) high loadings (∼48 wt %) of dendrimer-like PAMAM particles with average diameters of ∼1.3-2.4 μm, and (iii) matrices with sponge-like microstructures characteristics of membranes with strong mechanical integrity. Preliminary experiments show that these new mixed matrix PVDF membranes can serve as high capacity sorbents for Cu(II) recovery from aqueous solutions by ultrafiltration. PMID:26222014

  10. Alternating deposition films of a polymer and dendrimers bearing diphenylanthracene

    Institute of Scientific and Technical Information of China (English)

    SUN Jing; WANG Liyan; GAO Jian; YU Xi; WANG Zhiqiang

    2005-01-01

    Two generations of carboxyl-terminated poly (aryl ether) dendrimers bearing 9,10-diphenylanthracene cores are designed and synthesized. Alternating deposition of two dendrimers and poly(4-vinylpyridine) is studied with UV-Vis spectroscopy, FT-IR spectroscopy and atomic force microscopy. Experimental results indicate that this method to introduce chromophore into multilayer film can effectively prevent desorption of dye molecule. Moreover, it is found that dendrimer can inhibit the aggregation of fluorophore in film using fluorescence spectroscopy. Increase of dendrimer's generation can enhance fluorescence intensity of each fluorophore. This provides a new approach to design luminescent thin film.

  11. Dendrimers as a Potential Drug Delivery System: A Comprehensive Review

    Directory of Open Access Journals (Sweden)

    D. Nagasamy Venkatesh

    2015-07-01

    Full Text Available Dendrimers are synthetic, highly branched, monodisperse macromolecules of nanometer dimensions with exact and large number of functional groups, distributed with unprecedented control, makes them a promising scaffolds, for drug delivery. Dendrimers serves as an ideal vehicle for cancer therapy, immunology, vaccines, antivirals, biosensors for diagnostics, neuron capture therapy, photodynamic therapy and photo thermal therapy. Dendrimers chemistry is one of the most fascinating and rapidly expanding areas in the field of chemistry. Prior to the dendrimer technology, nanoparticle drug delivery systems were one of the choicest systems owing to their selectivity and stability of therapeutic agents incorporated into the system. However, few drawbacks such as reticuloendothelial system (RES uptake, drug leakage, immunogenicity, hemolytic toxicity, cytotoxicity, hydrophobicity etc., impede the usage of these nanostructures. Further, these shortcomings shall be circumvented by modifying the surface engineering, such as poly ester dendrimer, arginine dendrimer, glycol dendrimer, PEGylated dendrimers etc., Unique properties of uniform size, water solubility, modifiable surface functionality and availability of internal cavities makes them intriguing carrier for biological and drug delivery system. In the present review, we focused on the bioactive agents that can be easily encapsulated into the interior cavity (or chemical attachment, conjugation (or physically adsorbed on to the dendrimer surface to serve the desired properties of the carrier to cater specific needs of the active components, its characterization and application.

  12. Polyamidoamine nanoparticles as nanocarriers for the drug delivery to malaria parasite stages in the mosquito vector.

    Science.gov (United States)

    Urbán, Patricia; Ranucci, Elisabetta; Fernàndez-Busquets, Xavier

    2015-11-01

    Malaria is arguably one of the main medical concerns worldwide because of the numbers of people affected, the severity of the disease and the complexity of the life cycle of its causative agent, the protist Plasmodium spp. With the advent of nanoscience, renewed hopes have appeared of finally obtaining the long sought-after magic bullet against malaria in the form of a nanovector for the targeted delivery of antimalarial compounds exclusively to Plasmodium-infected cells, thus increasing drug efficacy and minimizing the induction of resistance to newly developed therapeutic agents. Polyamidoamine-derived nanovectors combine into a single chemical structure drug encapsulating capacity, antimalarial activity, low unspecific toxicity, specific targeting to Plasmodium, optimal in vivo activity and affordable synthesis cost. After having shown their efficacy in targeting drugs to intraerythrocytic parasites, now polyamidoamines face the challenge of spearheading a new generation of nanocarriers aiming at the malaria parasite stages in the mosquito vector.

  13. Dendrimers for Vaccine and Immunostimulatory Uses

    DEFF Research Database (Denmark)

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

    2010-01-01

    Dendrimers are well-defined (monodisperse) synthetic globular polymers with a range of interesting chemical and biological properties. Chemical properties include the presence of multiple accessible surface functional groups that can be used for coupling biologically relevant molecules and methods...... 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....

  14. Dendrimer effects on peptide and protein fibrillation

    DEFF Research Database (Denmark)

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

    2007-01-01

    , 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...

  15. Modified gold surfaces by 6-(ferrocenyl)hexanethiol/dendrimer/gold nanoparticles as a platform for the mediated biosensing applications

    Energy Technology Data Exchange (ETDEWEB)

    Karadag, Murat; Geyik, Caner; Demirkol, Dilek Odaci [Ege University, Faculty of Science, Biochemistry Department, 35100 Bornova-Izmir (Turkey); Ertas, F. Nil [Ege University, Faculty of Science, Chemistry Department, 35100, Bornova-Izmir (Turkey); Timur, Suna, E-mail: suna.timur@ege.edu.tr [Ege University, Faculty of Science, Biochemistry Department, 35100 Bornova-Izmir (Turkey)

    2013-03-01

    An electrochemical biosensor mediated by using 6-(Ferrocenyl) hexanethiol (FcSH) was fabricated by construction of gold nanoparticles (AuNPs) on the surface of polyamidoamine dendrimer (PAMAM) modified gold electrode. Glucose oxidase (GOx) was used as a model enzyme and was immobilized onto the gold surface forming a self assembled monolayer via FcSH and cysteamine. Cyclic voltammetry and amperometry were used for the characterization of electrochemical response towards glucose substrate. Following the optimization of medium pH, enzyme loading, AuNP and FcSH amount, the linear range for the glucose was studied and found as 1.0 to 5.0 mM with the detection limit (LOD) of 0.6 mM according to S/N = 3. Finally, the proposed Au/AuNP/(FcSH + Cyst)/PAMAM/GOx biosensor was successfully applied for the glucose analysis in beverages, and the results were compared with those obtained by HPLC. Highlights: Black-Right-Pointing-Pointer Immobilized mediator in SAM layer and dendrimeric structure to expand surface area. Black-Right-Pointing-Pointer Au nanoparticles for enhanced electron transfer. Black-Right-Pointing-Pointer Satisfactory Limit of Detection with 0.6 mM.

  16. Direct detection of OTA by impedimetric aptasensor based on modified polypyrrole-dendrimers.

    Science.gov (United States)

    Mejri-Omrani, Nawel; Miodek, Anna; Zribi, Becem; Marrakchi, Mouna; Hamdi, Moktar; Marty, Jean-Louis; Korri-Youssoufi, Hafsa

    2016-05-12

    Ochratoxin A (OTA) is a carcinogenic mycotoxin that contaminates food such as cereals, wine and beer; therefore it represents a risk for human health. Consequently, the allowed concentration of OTA in food is regulated by governmental organizations and its detection is of major agronomical interest. In the current study we report the development of an electrochemical aptasensor able to directly detect trace OTA without any amplification procedure. This aptasensor was constructed by coating the surface of a gold electrode with a film layer of modified polypyrrole (PPy), which was thereafter covalently bound to polyamidoamine dendrimers of the fourth generation (PAMAM G4). Finally, DNA aptamers that specifically binds OTA were covalently bound to the PAMAM G4 providing the aptasensor, which was characterized by using both Atomic Force Microscopy (AFM) and Surface Plasmon Resonance (SPR) techniques. The study of OTA detection by the constructed electrochemical aptasensor was performed using Electrochemical Impedance Spectroscopy (EIS) and revealed that the presence of OTA led to the modification of the electrical properties of the PPy layer. These modifications could be assigned to conformational changes in the folding of the aptamers upon specific binding of OTA. The aptasensor had a dynamic range of up to 5 μg L(-1) of OTA and a detection limit of 2 ng L(-1) of OTA, which is below the OTA concentration allowed in food by the European regulations. The efficient detection of OTA by this electrochemical aptasensor provides an unforeseen platform that could be used for the detection of various small molecules through specific aptamer association. PMID:27114221

  17. Synthesis, characterization and the release kinetics of antiproliferative agents from polyamidoamine conjugates.

    Science.gov (United States)

    Aderibigbe, B A; Sadiku, E R; Ray, S S; Mbianda, X Y; Fotsing, M C; Jayaramudu, J; Owonubi, S J

    2015-01-01

    Polyamidoamine conjugates containing curcumin and bisphosphonate were synthesized via a one-pot aqueous phase Michael addition reaction. In the design of the conjugate, bisphosphonate formed an integral part of the polymer carrier backbone. Curcumin was incorporated onto the polyamidoamine backbone via piperazine linker. The conjugates were characterized by Fourier transform spectroscopy, energy-dispersive X-ray analysis, atomic force spectroscopy and nuclear magnetic resonance spectroscopy and it confirmed the successful incorporation of the antiproliferative agents onto the carriers. The weight percentage incorporation of bisphosphonate to the carriers was found to be between 2.56% and 3.34%. The in vitro release studies of curcumin from the polyamidoamine conjugate were performed in dialysis bag at selected pH values. The release of curcumin was significantly slower at pH 7.4 when compared to pH 5.8. The release profiles indicate that the conjugates are more stable at pH 7.4 and are potential sustained drug-delivery systems for combination therapy.

  18. On the geometry and conformation of starburst dendrimers

    CERN Document Server

    De Pádua, A B; Moraes, F; Padua, Antonio de; Moraes, Fernando

    1995-01-01

    In this work, we propose a geometrical model for the study of conformational properties of a starburst dendrimer with the topology of a truncated Bethe lattice. A convenient embedding of the Bethe lattice in the hyperbolic plane is used to study the architecture of the dendrimer. As results, we find an upper bound for the molecular size and the density profile.

  19. Synthesis and Spectral Studies of CdTe–Dendrimer Conjugates

    Directory of Open Access Journals (Sweden)

    Ghosh Srabanti

    2009-01-01

    Full Text Available Abstract In order to couple high cellular uptake and target specificity of dendrimer molecule with excellent optical properties of semiconductor nanoparticles, the interaction of cysteine-capped CdTe quantum dots with dendrimer was investigated through spectroscopic techniques. NH2-terminated dendrimer molecule quenched the photoluminescence of CdTe quantum dots. The binding constants and binding capacity were calculated, and the nature of binding was found to be noncovalent. Significant decrease in luminescence intensity of CdTe quantum dots owing to noncovalent binding with dendrimer limits further utilization of these nanoassemblies. Hence, an attempt is made, for the first time, to synthesize stable, highly luminescent, covalently linked CdTe–Dendrimer conjugate in aqueous medium using glutaric dialdehyde (G linker. Conjugate has been characterized through Fourier transform infrared spectroscopy and transmission electron microscopy. In this strategy, photoluminescence quantum efficiency of CdTe quantum dots with narrow emission bandwidths remained unaffected after formation of the conjugate.

  20. 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. PMID:27267631

  1. Exciton migration and quenching in poly(propylene imine) dendrimers

    Science.gov (United States)

    Minevičiūtė, I.; Gulbinas, V.; Franckevičius, M.; Vaišnoras, R.; Marcos, M.; Serrano, J. L.

    2009-05-01

    Exciton migration between chromophore groups of the poly(propylene imine) dendrimer in chloroform solution and in solid state has been investigated by means of the time-resolved fluorescence measurements. Fluorescence decay kinetics, dynamic band shift and the depolarization rate have been analyzed. Exciton migration in a single dendrimer was found to be slow in comparison with temperature-dependent chromophore reorientation time of 150-600 ps. In a solid state chromophore groups form collective excitonic states responsible for the dendrimer film fluorescence. Exciton migration and localization to the lowest energy sites within the distributed density of states take place on a subnanosecond-nanosecond time scale.

  2. 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.

  3. Counterion Condensation and Effective Charge of PAMAM Dendrimers

    Directory of Open Access Journals (Sweden)

    Ulrich Scheler

    2011-04-01

    Full Text Available PAMAM dendrimers are used as a model system to investigate the effects of counterion condensation and the effective charge for spherical polyelectrolytes. Because of their amino groups, PAMAM dendrimers are weak polyelectrolytes. Lowering the pH results in an increasing protonation of the amino groups which is monitored via the proton chemical shifts of the adjacent CH2 groups. The effective charge is determined from a combination of diffusion and electrophoresis NMR. The fraction of the charges, which are effective for the interaction with an external electric field or other charges, decreases with increasing generation (size of the dendrimers.

  4. 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.

  5. 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.

  6. Using of Hyperbranched Poly(amidoamine as Pretanning Agent for Leather

    Directory of Open Access Journals (Sweden)

    Amal Amin Ibrahim

    2013-01-01

    Full Text Available Although chrome is considered as the major tanning agent in the production of all types of hides and leather worldwide, it represents a serious source of environmental pollution. Therefore, polyamidoamine hyperbranched polymer (HPAM was involved in pretanning of the depickled hides to enhance the chromium uptake during the tanning process. The key parameters which affect the exhaustion and fixation of chrome tan including shrinkage temperature of the tanned leather were studied. The results showed a significant improvement in the chrome exhaustion, the shrinkage temperature, and the texture and softness of the leather treated by HPAM.

  7. Intracellular Environment-Responsive Stabilization of Polymer Vesicles Formed from Head-Tail Type Polycations Composed of a Polyamidoamine Dendron and Poly(L-lysine

    Directory of Open Access Journals (Sweden)

    Kenji Kono

    2013-09-01

    Full Text Available For the development of effective drug carriers, nanocapsules that respond to micro-environmental changes including a decrease in pH and a reductive environment were prepared by the stabilization of polymer vesicles formed from head-tail type polycations, composed of a polyamidoamine dendron head and a poly(L-lysine tail (PAMAM dendron-PLL, through the introduction of disulfide bonds between the PLL tails. Disulfide bonds were successfully introduced through the reaction of Lys residues in the PAMAM dendron-PLL polymer vesicles with 2-iminothiolane. The stabilization of PAMAM dendron-PLL polymer vesicles was confirmed by dynamic light scattering measurements. In acid-base titration experiments, nanocapsules cross-linked by disulfide bonds had a buffering effect during the cellular uptake process. The PAMAM dendron-PLL nanocapsules were used to incorporate the fluorescent dyes rhodamine 6G and fluorescein as a drug model. Cationic rhodamine 6G was generally not released from the nanocapsules because of the electrostatic barrier of the PLL membrane. However, the nanocapsules were destabilized at high glutathione concentrations corresponding to intracellular concentrations. Rhodamine 6G was immediately released from the nanocapsules because of destabilization upon the cleavage of disulfide bonds. This release of rhodamine 6G from the nanocapsules was also observed in HeLa cells by laser confocal microscopy.

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

    International Nuclear Information System (INIS)

    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

  9. 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.

  10. Low potential stable glucose detection at dendrimers modified polyaniline nanotubes

    OpenAIRE

    Alessandra Nogueira Santos; Demétrio Artur Werner Soares; Alvaro Antonio Alencar de Queiroz

    2010-01-01

    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 ...

  11. Host-Guest Chemistry of Dendrimers in the Gas Phase

    OpenAIRE

    Qi, Zhenhui; Schalley, Christoph A

    2010-01-01

    Abstract Since the early days of dendrimer chemistry, mass spectrometry has been an important analytical method for determining the purity and the detection of defects in dendrimers. Meanwhile, growing evidence demonstrates the great potential of mass spectrometry for the investigation of non-covalent dendritic host-guest complexes. Mass spectrometry provides an efficient means to isolate them in the high vacuum inside a mass spectrometer under environment-free conditions. Gas-phas...

  12. Synthesis and Investigation of Soluble Polymer-supported Dendrimers

    Institute of Scientific and Technical Information of China (English)

    XIE, Cheng; LU, Cui-Fen; CHEN, Zu-Xing; YANG, Gui-Chun

    2006-01-01

    Poly(ethylene glycol) (PEG)-supported dendrimers have been synthesized using 2,4,6-trichloro-1,3,5-triazine(TCT) as dendrons and tris(hydroxymethyl)aminomethane as linkers with high loading capacity, excellent solubility and thermal stability by divergent method. The new synthesized PEG-supported G2.0 dendrimer has 10 times as large functional group loading capacity as commercial PEG3400 with overall yield 44.0%.

  13. Hyaluronic acid-modified manganese-chelated dendrimer-entrapped gold nanoparticles for the targeted CT/MR dual-mode imaging of hepatocellular carcinoma

    Science.gov (United States)

    Wang, Ruizhi; Luo, Yu; Yang, Shuohui; Lin, Jiang; Gao, Dongmei; Zhao, Yan; Liu, Jinguo; Shi, Xiangyang; Wang, Xiaolin

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. The early and effective diagnosis has always been desired. Herein, we present the preparation and characterization of hyaluronic acid (HA)-modified, multifunctional nanoparticles (NPs) targeting CD44 receptor-expressing cancer cells for computed tomography (CT)/magnetic resonance (MR) dual-mode imaging. We first modified amine-terminated generation 5 poly(amidoamine) dendrimers (G5.NH2) with an Mn chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), fluorescein isothiocyanate (FI), and HA. Then, gold nanoparticles (AuNPs) were entrapped within the above raw product, denoted as G5.NH2-FI-DOTA-HA. The designed multifunctional NPs were formed after further Mn chelation and purification and were denoted as {(Au0)100G5.NH2-FI-DOTA(Mn)-HA}. These NPs were characterized via several different techniques. We found that the {(Au0)100G5.NH2-FI-DOTA(Mn)-HA} NPs exhibited good water dispersibility, stability under different conditions, and cytocompatibility within a given concentration range. Because both AuNPs and Mn were present in the product, {(Au0)100G5.NH2-FI-DOTA(Mn)-HA} displayed a high X-ray attenuation intensity and favorable r1 relaxivity, which are advantageous properties for targeted CT/MR dual-mode imaging. This approach was used to image HCC cells in vitro and orthotopically transplanted HCC tumors in a unique in vivo model through the CD44 receptor-mediated endocytosis pathway. This work introduces a novel strategy for preparing multifunctional NPs via dendrimer nanotechnology. PMID:27653258

  14. Invertase-labeling gold-dendrimer for in situ amplified detection mercury(II) with glucometer readout and thymine-Hg(2+)-thymine coordination chemistry.

    Science.gov (United States)

    Qiu, Zhenli; Shu, Jian; Jin, Guixiao; Xu, Mingdi; Wei, Qiaohua; Chen, Guonan; Tang, Dianping

    2016-03-15

    A simple, low-cost transducer with glucometer readout was designed for sensitive detection of mercury(II) (Hg(2+)), coupling with thymine-Hg(2+)-thymine (T-Hg(2+)-T) coordination chemistry and invertase-functionalized gold-dendrimer nanospheres for the signal amplification. Initially, nanogold-encapsulated poly(amidoamine) dendrimers (Au DENs) were synthesized by in-situ reduction of gold(III). Thereafter, the as-prepared Au DENs were utilized for the labeling of invertase and T-rich signal DNA probe. In the presence of target Hg(2+), the functionalized Au DENs were conjugated to capture DNA probe-modified electrode via T-Hg(2+)-T coordination chemistry. Accompanying the Au DENs, the labeled invertase could hydrolyze sucrose into glucose, which could be quantitatively monitored by an external personal glucometer (PGM). The PGM signal increased with the increasing target Hg(2+) in the sample. Under the optimal conditions, our designed sensing platform exhibited good PGM responses toward target Hg(2+), and allowed the detection of Hg(2+) at a concentration as low as 4.2 pM. This sensing system also displayed remarkable specificity relative to target Hg(2+) against other competing ions, and could be applied for reliable monitoring of spiked Hg(2+) into the environmental water samples with satisfactory results. With the advantages of cost-effectiveness, simplicity, portability, and convenience, our strategy provides a tremendous potential to be a promising candidate for point-of-use monitoring of non-glucose targets by the public.

  15. Hyaluronic acid-modified manganese-chelated dendrimer-entrapped gold nanoparticles for the targeted CT/MR dual-mode imaging of hepatocellular carcinoma

    Science.gov (United States)

    Wang, Ruizhi; Luo, Yu; Yang, Shuohui; Lin, Jiang; Gao, Dongmei; Zhao, Yan; Liu, Jinguo; Shi, Xiangyang; Wang, Xiaolin

    2016-09-01

    Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. The early and effective diagnosis has always been desired. Herein, we present the preparation and characterization of hyaluronic acid (HA)-modified, multifunctional nanoparticles (NPs) targeting CD44 receptor-expressing cancer cells for computed tomography (CT)/magnetic resonance (MR) dual-mode imaging. We first modified amine-terminated generation 5 poly(amidoamine) dendrimers (G5.NH2) with an Mn chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), fluorescein isothiocyanate (FI), and HA. Then, gold nanoparticles (AuNPs) were entrapped within the above raw product, denoted as G5.NH2-FI-DOTA-HA. The designed multifunctional NPs were formed after further Mn chelation and purification and were denoted as {(Au0)100G5.NH2-FI-DOTA(Mn)-HA}. These NPs were characterized via several different techniques. We found that the {(Au0)100G5.NH2-FI-DOTA(Mn)-HA} NPs exhibited good water dispersibility, stability under different conditions, and cytocompatibility within a given concentration range. Because both AuNPs and Mn were present in the product, {(Au0)100G5.NH2-FI-DOTA(Mn)-HA} displayed a high X-ray attenuation intensity and favorable r1 relaxivity, which are advantageous properties for targeted CT/MR dual-mode imaging. This approach was used to image HCC cells in vitro and orthotopically transplanted HCC tumors in a unique in vivo model through the CD44 receptor-mediated endocytosis pathway. This work introduces a novel strategy for preparing multifunctional NPs via dendrimer nanotechnology.

  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. Wiring of Glucose Oxidizing Flavin Adenine Dinucleotide-Dependent Enzymes by Methylene Blue-Modified Third Generation Poly(amidoamine) Dendrimers Attached to Spectroscopic Graphite Electrodes

    DEFF Research Database (Denmark)

    Castaing, Victor; Álvarez-Martos, Isabel; Ferapontova, Elena

    2016-01-01

    Electro-enzymatic biotransformation requires an efficient and robust electronic communication between the biomolecules and electrodes, often performed by the relevant electron transfer (ET) mediating systems. Of those, redox-labeled dendrimeric structures, biocompatible and bearing spatially orde...

  18. Development and in vitro Evaluation of Antigen-Loaded Poly(amidoamine) Nanoparticles for Respiratory Epithelium Applications

    NARCIS (Netherlands)

    Coué, G.M.J.P.C.; Hermanns, I.; Unger, R.E.; Kirkpatrick, C.J.; Engbersen, J.F.J.

    2013-01-01

    A poly(amidoamine) with disulfide linkages in the main chain and 4-hydroxybutyl and ω-carboxy-PEG groups (9:1 ratio) as side chains was prepared by Michael addition polymerization of cystamine bisacrylamide with 4-hydroxybutylamine and ω-carboxy-PEG-amine. To develop therapeutic protein formulations

  19. DESIGN AND PHOTOFUNCTIONS OF DENDRIMER-ENCAPSULATED POLY(PHENYLENEETHYNYLENE)S

    Institute of Scientific and Technical Information of China (English)

    Dong-lin Jiang; Takafumi Sato; Takuzo Aida

    2001-01-01

    A series of dendrimer-encapsulated poly(phenyleneethynylene)s 4~6 were synthesized. The light-harvesting antenna fimctions of dendrimer frameworks together with the blue-light emitting activities of 4~6 were highlighted.

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

    International Nuclear Information System (INIS)

    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

  1. A Cytochrome P450 3A4 Biosensor Based on Generation 4.0 PAMAM Dendrimers for the Detection of Caffeine.

    Science.gov (United States)

    Müller, Michael; Agarwal, Neha; Kim, Jungtae

    2016-01-01

    Cytochromes P450 (CYP, P450) are a large family of heme-active-site proteins involved in many catalytic processes, including steroidogenesis. In humans, four primary enzymes are involved in the metabolism of almost all xenobiotics. Among these enzymes, CYP3A4 is responsible for the inactivation of the majority of used drugs which makes this enzyme an interesting target for many fields of research, especially pharmaceutical research. Since the late 1970s, attempts have been made to construct and develop electrochemical sensors for the determination of substrates. This paper is concerned with the establishment of such a CYP3A4-containing biosensor. The sensor was constructed by adsorption of alternating layers of sub-nanometer gold particle-modified PAMAM (poly-amido-amine) dendrimers of generation 4.0, along with the enzyme by a layer-by-layer assembly technique. Atomic force microscopy (AFM), quartz crystal microbalance (QCM), and Fourier-transformed infrared spectroscopy (FTIR) were employed to elucidate the sensor assembly. Additionally, the biosensor was tested by cyclic voltammetry using caffeine as a substrate. PMID:27548239

  2. An enhanced biosensor for glutamate based on self-assembled carbon nanotubes and dendrimer-encapsulated platinum nanobiocomposites-doped polypyrrole film

    Energy Technology Data Exchange (ETDEWEB)

    Tang Longhua [Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Zhu Yihua [Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China)]. E-mail: yhzhu@ecust.edu.cn; Yang Xiaoling [Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Li Chunzhong [Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China)

    2007-07-30

    An enhanced amperometric biosensor based on incorporating one kind of unique nanobiocomposite as dopant within an electropolymerized polypyrrole film has been investigated. The nanobiocomposite was synthesized by self-assembling glutamate dehydrogenase (GLDH) and poly(amidoamine) dendrimer-encapsulated platinum nanoparticles (Pt-DENs) onto multiwall carbon nanotubes (CNTs). {zeta}-Potentials and high-resolution transmission electron microscopy (HRTEM) confirmed the uniform growth of the layer-by-layer nanostructures onto the carboxyl-functionalized CNTs. The size of Pt nanoparticles is approximately 3 nm. The (GLDH/Pt-DENs) {sub n}/CNTs/Ppy hybrid film was obtained by electropolymerization of pyrrole onto glassy carbon electrodes and characterized with scanning electron microscopy (SEM), cyclic voltammetry (CV) and other electrochemical measurements. All methods indicated that the (GLDH/Pt-DENs) {sub n}/CNTs nanobiocomposites were entrapped within the porous polypyrrole film and resulted in a hybrid film that showed a high electrocatalytic ability toward the oxidation of glutamate at a potential 0.2 V versus Ag/AgCl. The biosensor shows performance characteristics with high sensitivity (51.48 {mu}A mM{sup -1}), rapid response (within 3 s), low detection limit (about 10 nM), low level of interference and excellent reproducibility and stability.

  3. A Cytochrome P450 3A4 Biosensor Based on Generation 4.0 PAMAM Dendrimers for the Detection of Caffeine

    Science.gov (United States)

    Müller, Michael; Agarwal, Neha; Kim, Jungtae

    2016-01-01

    Cytochromes P450 (CYP, P450) are a large family of heme-active-site proteins involved in many catalytic processes, including steroidogenesis. In humans, four primary enzymes are involved in the metabolism of almost all xenobiotics. Among these enzymes, CYP3A4 is responsible for the inactivation of the majority of used drugs which makes this enzyme an interesting target for many fields of research, especially pharmaceutical research. Since the late 1970s, attempts have been made to construct and develop electrochemical sensors for the determination of substrates. This paper is concerned with the establishment of such a CYP3A4-containing biosensor. The sensor was constructed by adsorption of alternating layers of sub-nanometer gold particle-modified PAMAM (poly-amido-amine) dendrimers of generation 4.0, along with the enzyme by a layer-by-layer assembly technique. Atomic force microscopy (AFM), quartz crystal microbalance (QCM), and Fourier-transformed infrared spectroscopy (FTIR) were employed to elucidate the sensor assembly. Additionally, the biosensor was tested by cyclic voltammetry using caffeine as a substrate. PMID:27548239

  4. Synthesis and evaluation in vitro in cancer cells AR42J of the radiopharmaceutical 99mTc-Tyr3-Octreotide-dendrimer similar of somatostatin

    International Nuclear Information System (INIS)

    The objective of this project was preparing a multimeric system through the conjugation of several molecules of the peptide Tyr3-Octreotide to a dendrimer molecule based on Poly-amidoamine (PAMAM), as well as radiolabeled with 99mTc and evaluating its behavior like new radiopharmaceutical similar of somatostatin. The dendrimer PAMAM generation 3.5 that possesses terminal groups of sodium carboxylate, was functionalized to peptide Tyr3-Octreotide through a reaction of peptide coupling with HATU (hexafluorophosphate (V) of 1-oxide-3-(bis(dimethylamino)methylene)-3H-[1,2,3]triazole[4,5-b]pyridine) as activating agent of carboxylate groups using the Size Exclusion Chromatography (Sec) as purification method. The product was characterized by Ultraviolet visible spectrophotometry, Mid-infrared and Far-infrared, Elemental analysis, Energy dispersive X-ray spectroscopy, Scanning electron microscopy, Thermogravimetry and Differential scanning calorimetry. The radiolabeled with 99mTc was carried out using a direct method that involves the reduction of the anion TcO4- with stannous chloride, so that the dendrimer is capable of coordinating to the technetium forming a chelate compound. The radiochemical purity of the radiolabeled compound was determined by thin layer chromatography using a sodium chloride solution to 20% (m/v) as mobile phase and was verified by molecular exclusion chromatography. The radiolabeled compound was possible to obtain it with a radiochemical purity superior to 90%. Also, the specific and not specific union was evaluated of the synthesized compound in mouse pancreas cancer cells AR42J, positive to somatostatin receptors, showing specific recognition for this receptors type with high cellular internalization. The biodistribution studies were carried out in BALB/c mice at different post injection times and in nude mice with induced tumors AR42J. The results showed that the 99mTc-PAMAM-Tyr3-Octreotide is excreted by via renal as hepatobiliary with a

  5. Potential Antitumor Dendrimers: Synthesis and Characterizations of Rhenium(Ⅰ) and Cis-platin Containing Dendrimers

    Institute of Scientific and Technical Information of China (English)

    Zhao Xinxin; Chit-Kay Chu

    2005-01-01

    @@ 1Introduction The chemistry of dendrimers is a fast developing field and has brought about a tsunami of research activity since Vogtle reported the first preparation in 1978. These hyperbranched macromolecules have grown out of chemists' imagination and have challenged synthetic chemists with their architectural complexity and intriguity. The potentials of these macromolecules are extensive and are synthesized using both organic and inorganic cores from which different scaffoldings are built, and upon which functionalities are attached for specific applications. The synthesis and characterizations of cisplatin and rhenium(Ⅰ) containing PAMAM derivatives will be discussed.

  6. Synthesis, aggregation, and chiroptical properties of chiral, amphiphilic dendrimers.

    Science.gov (United States)

    Laufersweiler, M J; Rohde, J M; Chaumette, J L; Sarazin, D; Parquette, J R

    2001-09-21

    The syntheses of amphiphilic dendrimers based on 3,5-dihydroxybenzyl alcohol containing tri- or tetrafunctional chiral central cores and allyl ester termini are described. Water solubility is imparted to the dendrimers via a palladium-catalyzed deprotection of the peripheral allyl esters. This method affords complete deprotection of the carboxylate surface because, in contrast to the basic hydrolysis of methyl ester termini, the solubility of partially hydrolyzed intermediates is maintained throughout the course of the deprotection, thereby avoiding precipitation during the reaction. Chiroptical analysis indicates that the structure of the dendrimers collapses in water, resulting in an increased steric effect upon the central core that is manifested by lower optical rotatory power. However, contributions to the chiroptical properties from the dendron branch segments were not evident in water or organic media, suggesting that chiral substructures were not developing in the branch segments of the dendrimers. Multiangle light scattering studies revealed that the dendrimers experienced significant aggregation in aqueous media that decreased at higher generations. This behavior could be rationalized by a change in conformational preference from a disklike conformation at low generations to a more globular conformation at higher generations. PMID:11559197

  7. Modeling Dendrimers Charge Interaction in Solution: Relevance in Biosystems

    Directory of Open Access Journals (Sweden)

    Domenico Lombardo

    2014-01-01

    Full Text Available Dendrimers are highly branched macromolecules obtained by stepwise controlled, reaction sequences. The ability to be designed for specific applications makes dendrimers unprecedented components to control the structural organization of matter during the bottom-up synthesis of functional nanostructures. For their applications in the field of biotechnology the determination of dendrimer structural properties as well as the investigation of the specific interaction with guest components are needed. We show how the analysis of the scattering structure factor S(q, in the framework of current models for charged systems in solution, allows for obtaining important information of the interdendrimers electrostatic interaction potential. The finding of the presented results outlines the important role of the dendrimer charge and the solvent conditions in regulating, through the modulation of the electrostatic interaction potential, great part of the main structural properties. This charge interaction has been indicated by many studies as a crucial factor for a wide range of structural processes involving their biomedical application. Due to their easily controllable properties dendrimers can be considered at the crossroad between traditional colloids, associating polymers, and biological systems and represent then an interesting new technological approach and a suitable model system of molecular organization in biochemistry and related fields.

  8. MONODISPERSED AND NANOSIZED DENDRIMER/POLYSTYRENE LATEX PARTICLES

    Institute of Scientific and Technical Information of China (English)

    Changfeng Yi; Zushun Xu; Warren T. Ford

    2004-01-01

    Emulsion polymerization of styrene was carried out using dendrimer DAB-dendr-(NH2)64 as seed. The size and size distribution of the emulsion particles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS), and the effects of emulsion polymerization conditions on the preparation of emulsion particle were investigated. It has been found that the nanosized dendrimer/polystyrene polymer emulsion particles obtained were in the range of 26~64 nm in diameter, and were monodisperse; the size and size distribution of emulsion particles were influenced by the contents of dendrimer DAB-dendr-(NH2)64, emulsifier and initiator, as well as the pH value.

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

    Science.gov (United States)

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

    2016-01-01

    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. PMID:27347913

  10. Recent advances in click chemistry applied to dendrimer synthesis.

    Science.gov (United States)

    Arseneault, Mathieu; Wafer, Caroline; Morin, Jean-François

    2015-01-01

    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. PMID:26007183

  11. 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.

  12. 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.

  13. Two Dimensional Aggregation Behaviors of Quinoxaline Dendrimers.

    Science.gov (United States)

    Choi, Soyoung; Lee, Hoik; Kim, Hwan Kyu; Lee, Sang Uck; Sohn, Daewon

    2015-02-01

    This study focuses on the molecular behavior of two dendrimers containing a hydrophilic core group (carboxyl group) and hydrophobic branches (quinoxaline and methoxyphenyl groups), 2,3-bis(4-(2,3- bis(4-methoxyphenyl)quinoxalin-6-yloxy)phenyl)quinoxaline-6-carb-oxylic acid (G2) and 2,3-bis(4-(2,3-bis(4-(2,3-bis(4-methoxyphenyl)quinoxalin-6-yloxy)phe-nyl)quinoxalin-6-y-oxy)phenyl) quin oxaline-6-carboxylic acid (G3) at the air-water interface. To understand the mechanism of the self-assembly of these molecules, we measured the surface pressure-area (III-A) isotherm and investigated the surface morphology of Langmuir-Blodgett films transferred onto hydrophilic silicon wafers using atomic force microscopy (AFM). Upon compression, G2 molecules stand up and steadily make close-packed monolayer whereas G3 molecules form circular domains and gradually make aggregates of domains. These results were confirmed by the X-ray Reflectivity (XRR) profiles of G2 and G3 monolayers transferred onto silicon substrates.

  14. Electrical Properties of Multi-Pyrene/Porphyrin-Dendrimers

    Directory of Open Access Journals (Sweden)

    Mark Euguenii Martínez-Klimov

    2015-09-01

    Full Text Available Dendrimers bearing pyrene donor groups have been obtained and act as efficient light-harvesting antennae capable of transferring light energy through space from their periphery to their core. The light-harvesting ability increases with each generation due to an increase in the number of peripheral pyrenes. In order to evaluate the photovoltaic properties of the compounds, thermal evaporated thin films were produced and the voltage response in the presence of visible light was obtained. The energy transfer efficiency was found to be almost quantitative for the first and second generations. The dendrimers have the potential to become integral components of molecular photonic devices.

  15. 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.

  16. Carboxymethyl chitosan-modified magnetic-cored dendrimer as an amphoteric adsorbent.

    Science.gov (United States)

    Kim, Hye-Ran; Jang, Jun-Won; Park, Jae-Woo

    2016-11-01

    Carboxymethyl chitosan-modified magnetic-cored dendrimers (CCMDs) were successfully synthesized in a three step method. The synthesized samples were characterized using X-ray diffraction, transmission electron microscopy, scanning electron microscopy, vibrating sample magnetometer, thermogravimetry analysis, zeta potential analyzer, X-ray photoelectron spectroscopy, surface area analysis, and Fourier transform infrared spectroscopy. The CCMD exhibited selective adsorption for anionic and cationic compounds at specific pH conditions. With the substitution of amino groups of MD with carboxymethyl chitosan moieties, the adsorption sites for cationic compounds were greatly increased. Since the adsorption onto CCMD was mainly electrostatic interaction, the adsorption of MB and MO was significantly affected by the pHs. The optimal adsorption pH values were 3 and 11 for MO and MB. The maximal adsorption of MO and MB on the CCMD at pH values of 3 and 11 were 20.85mgg(-1) and 96.31mgg(-1), respectively. Reuse of the CCMD as an adsorbent was experimentally tested through adsorption and desorption with simple pH control. More than 99% and 91% of the initial adsorption of MB and MO on the CCMD was maintained with five consecutive recycling. PMID:27351905

  17. Dye adsorption of cotton fabric grafted with PPI dendrimers: Isotherm and kinetic studies.

    Science.gov (United States)

    Salimpour Abkenar, Samera; Malek, Reza Mohammad Ali; Mazaheri, Firouzmehr

    2015-11-01

    In this research, the cotton fabrics grafted with two generations of the poly(propylene imine) dendrimers were applied to adsorb textile dyes from aqueous solutions. Direct Red 80 (anionic dye), Disperse Yellow 42 (nonionic dye) and Basic Blue 9 (cationic dye) were selected as model dyes. The effect of various experimental parameters such as initial concentration of dyes, charge of dyes molecule, salt and pH was investigated on the adsorption process. Furthermore, kinetics and equilibrium of the adsorption process on the grafted samples were studied. It was found that maximum adsorption of anionic and disperse dyes took place at around pH 3, while cationic dye could be adsorbed at around pH 11. The Langmuir equation was able to describe the mechanism of dyes adsorption. In addition, the second-order equation was found to be fit with the kinetics data. Interestingly, it seems that the dye adsorption of the grafted fabrics is strongly pH dependent.

  18. Linear biocompatible glyco-polyamidoamines as dual action mode virus infection inhibitors with potential as broad-spectrum microbicides for sexually transmitted diseases

    Science.gov (United States)

    Mauro, Nicolò; Ferruti, Paolo; Ranucci, Elisabetta; Manfredi, Amedea; Berzi, Angela; Clerici, Mario; Cagno, Valeria; Lembo, David; Palmioli, Alessandro; Sattin, Sara

    2016-09-01

    The initial steps of viral infections are mediated by interactions between viral proteins and cellular receptors. Blocking the latter with high-affinity ligands may inhibit infection. DC-SIGN, a C-type lectin receptor expressed by immature dendritic cells and macrophages, mediates human immunodeficiency virus (HIV) infection by recognizing mannose clusters on the HIV-1 gp120 envelope glycoprotein. Mannosylated glycodendrimers act as HIV entry inhibitors thanks to their ability to block this receptor. Previously, an amphoteric, but prevailingly cationic polyamidoamine named AGMA1 proved effective as infection inhibitor for several heparan sulfate proteoglycan-dependent viruses, such as human papilloma virus HPV-16 and herpes simplex virus HSV-2. An amphoteric, but prevailingly anionic PAA named ISA23 proved inactive. It was speculated that the substitution of mannosylated units for a limited percentage of AGMA1 repeating units, while imparting anti-HIV activity, would preserve the fundamentals of its HPV-16 and HSV-2 infection inhibitory activity. In this work, four biocompatible linear PAAs carrying different amounts of mannosyl-triazolyl pendants, Man-ISA7, Man-ISA14, Man-AGMA6.5 and Man-AGMA14.5, were prepared by reaction of 2-(azidoethyl)-α-D-mannopyranoside and differently propargyl-substituted AGMA1 and ISA23. All mannosylated PAAs inhibited HIV infection. Both Man-AGMA6.5 and Man-AGMA14.5 maintained the HPV-16 and HSV-2 activity of the parent polymer, proving broad-spectrum, dual action mode virus infection inhibitors.

  19. A New Convergent Approach to Unsymmetrically Branched Polyether Dendrimers

    Institute of Scientific and Technical Information of China (English)

    GAO Xiaoping; WANG Feng; WANG Xiaolong; ZHOU Zhaoli

    2001-01-01

    @@ Dendrimers are perfect monodisperse macromolecules with a regular and highly branched three-dimensional architecture. The combination of discrete numbers of functionality in one molecular and high densities of active groups, typical for dendritic molecules, has attracted a lot of attention in the fields of medicinal chenistry (e.g. in drug delivery system), host-guest chemistry and catalysis chemistry[1].

  20. Antiviral mechanism of polyanionic carbosilane dendrimers against HIV-1

    Science.gov (United States)

    Vacas-Córdoba, Enrique; Maly, Marek; De la Mata, Francisco J; Gómez, Rafael; Pion, Marjorie; Muñoz-Fernández, Mª Ángeles

    2016-01-01

    Nanotechnology-derived platforms, such as dendrimers, are very attractive in several biological applications. In the case of human immunodeficiency virus (HIV) infection, polyanionic carbosilane dendrimers have shown great potential as antiviral agents in the development of novel microbicides to prevent the sexual transmission of HIV-1. In this work, we studied the mechanism of two sulfated and naphthylsulfonated functionalized carbosilane dendrimers, G3-S16 and G2-NF16. They are able to inhibit viral infection at fusion and thus at the entry step. Both compounds impede the binding of viral particles to target cell surface and membrane fusion through the blockage of gp120–CD4 interaction. In addition, and for the first time, we demonstrate that dendrimers can inhibit cell-to-cell HIV transmission and difficult infectious synapse formation. Thus, carbosilane dendrimers’ mode of action is a multifactorial process targeting several proteins from viral envelope and from host cells that could block HIV infection at different stages during the first step of infection. PMID:27103798

  1. Fluorophore-cored dendrimers for patterns in metalloprotein sensing.

    Science.gov (United States)

    Jiwpanich, Siriporn; Sandanaraj, Britto S; Thayumanavan, S

    2009-02-21

    In fluorophore-cored dendrimers with peripheral binding functionalities, the effect of generation upon protein binding-induced fluorescence quenching can be unpredictable; this is because the increase in fluorophore-binding functionality distance with generation is also accompanied by an increase in the number of binding moieties and the interplay between the two features is utilized to create patterns for metalloprotein sensing.

  2. 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

  3. Copper Granule-Catalyzed Microwave-Assisted Click Synthesis of Polyphenol Dendrimers

    OpenAIRE

    Lee, Choon Young; Held, Rich; Sharma, Ajit; Baral, Rom; Nanah, Cyprien; Dumas, Dan; Jenkins, Shannon; Upadhaya, Samik; Du, Wenjun

    2013-01-01

    Syringaldehyde and vanillin-based antioxidant dendrimers were synthesized via microwave-assisted alkyne-azide 1,3-dipolar cycloaddition using copper granules as a catalyst. The use of Cu(I) as a catalyst resulted in copper contaminated dendrimers. In order to produce copper-free antioxidant dendrimers for biological applications, Cu(I) was substituted with copper granules. Copper granules were ineffective at both room temperature and under reflux conditions (< 5% yield). However, it was an ex...

  4. pH controlled gating of toxic protein pores by dendrimers.

    Science.gov (United States)

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

    2016-07-14

    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. PMID:27328315

  5. Energy and Electron Transfer Studies of Triarylamine-based Dendrimers and Cascades

    OpenAIRE

    Zieschang, Fabian

    2014-01-01

    In this work the synthesis of dendritic macromolecules and small redox cascades was reported and studies of their energy and electron transfer properties discussed. The chromophores in the dendrimers and the redox cascades are linked via triazoles, which were built up by CuAAC. Thereby, a synthetic concept based on building blocks was implemented, which allowed the exchange of all basic components. Resulting structures include dendrimers composed exclusively of TAAs (G1–G3), dendrimers wit...

  6. Dendrimers Containing Ferrocene and Porphyrin Moieties: Synthesis and Cubic Non-Linear Optical Behavior

    OpenAIRE

    Eric G. Morales-Espinoza; Sanchez-Montes, Karla E.; Elena Klimova; Tatiana Klimova; Lijanova, Irina V.; Maldonado, José L.; Gabriel Ramos-Ortíz; Simón Hernández-Ortega; Marcos Martínez-García

    2010-01-01

    Dendrons with ferrocenyl ended groups joined by styryl moieties were attached to a porphyrin core. All the dendrons used for dendrimer synthesis showed trans configuration. The chemical structure of the first generation dendron was confirmed by X-ray crystallographic studies. The structure of the synthesized dendrimers was confirmed by 1H- and 13C-NMR, electrospray mass spectrometry and elemental analysis. Cubic non-linear optical behavior of the ferrocene and porphyrin-containing dendrimers ...

  7. Novel PH Sensitive Nanocarrier Agents Based on Citric Acid Dendrimers Containing Conjugated β-Cyclodextrins

    Directory of Open Access Journals (Sweden)

    Hassan Namazi

    2011-06-01

    Full Text Available Introduction: In this work, the use of β-cyclodextrine (β-CD-modified dendrimers as a nanocapsule with a biocompatible shell have studied. β-CD-modified dendrimers have designed and synthesized to enhance the loading capacity of the final dendrimers with encapsulation properties. Methods: To achieve β-CD-modified dendrimers, first citric acid dendrimers were synthesized and then the end functional groups of dendrimers were grafted to β-CD through ester linkages. The molecular structures of resulted dendrimers were verified using common spectroscopic methods such as 1H NMR, FT-IR and the diameters of obtained nanocarriers were evaluated with using dynamic light scattering (DLS experiments. The isolated dendrimers were utilized as the drug delivery agents and the encapsulation and the controlled release of guest drug molecule Naltrexone (NLX was investigated in different pH’s using UV spectroscopy method. Results: It was established that the loading capacity of dendrimers depend on several factors such as their generation and the structure and number of conjugated modifier end groups. Conclusion: Increasing in the number of branches and the size of interior voids and number of conjugated β-CDs cause to enhance the loading capacity.

  8. 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

    2015-10-01

    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.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

  9. Surface interactions induced by polyelectrolytes, dendrimers, and dendronized polymers

    OpenAIRE

    Popa, Ionel

    2010-01-01

    Dans cette thèse, les interactions de surfaces induites par des polyélectrolytes linéaires, des dendrimères et des polymères dendronizés ont été étudiées. Les études ont été menées avec la microscopie à force atomique (AFM) et complétées par la réflectométrie. Première, l'influence de la force ionique sur l'adsorption de polyélectrolytes linéaires et du dendrimères sur des surfaces de silice planaires est étudiée. Les plateaux d'adsorption augmentent fortement avec la force ionique. Après, le...

  10. Recent Advances in Click Chemistry Applied to Dendrimer Synthesis

    OpenAIRE

    Mathieu Arseneault; Caroline Wafer; Jean-François Morin

    2015-01-01

    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...

  11. A New Convergent Approach to Unsymmetrically Branched Polyether Dendrimers

    Institute of Scientific and Technical Information of China (English)

    GAO; Xiaoping

    2001-01-01

    Dendrimers are perfect monodisperse macromolecules with a regular and highly branched three-dimensional architecture. The combination of discrete numbers of functionality in one molecular and high densities of active groups, typical for dendritic molecules, has attracted a lot of attention in the fields of medicinal chenistry (e.g. in drug delivery system), host-guest chemistry and catalysis chemistry[1].  ……

  12. Optimized dendrimer-encapsulated gold nanoparticles and enhanced carbon nanotube nanoprobes for amplified electrochemical immunoassay of E. coli in dairy product based on enzymatically induced deposition of polyaniline.

    Science.gov (United States)

    Zhang, Xinai; Shen, Jianzhong; Ma, Haile; Jiang, Yuxiang; Huang, Chenyong; Han, En; Yao, Boshui; He, Yunyao

    2016-06-15

    A highly sensitive immunosensor was reported for Escherichia coli assay in dairy product based on electrochemical measurement of polyaniline (PAn) that was catalytically deposited by horseradish peroxidase (HRP) labels. Herein, the immunosensor was developed by using poly(amidoamine) dendrimer-encapsulated gold nanoparticles (PAMAM(Au)) as sensing platform. Importantly, the optimal HAuCl4/PAMAM ratio was investigated to design the efficient PAMAM(Au) nanocomposites. The nanocomposites were proven to not only increase the amount of immobilized capture antibody (cAb), but also accelerate the electron transfer process. Moreover, the {dAb-CNT-HRP} nanoprobes were prepared by exploiting the amplification effect of multiwalled carbon nanotubes (CNTs) for loading detection antibody (dAb) and enormous HRP labels. After a sandwich immunoreaction, the quantitatively captured nanoprobes could catalyze oxidation aniline to produce electroactive PAn for electrochemical measurement. On the basis of signal amplification of the PAMAM(Au)-based immunosensor and the {dAb-CNT-HRP} nanoprobes, the proposed strategy exhibited a linear relationship between the peak current of PAn and the logarithmic value of E. coli concentration ranging from 1.0 × 10(2) to 1.0 × 10(6) cfu mL(-1) with a detection limit of 50 cfu mL(-1) (S/N=3), and the electrochemical detection of E. coli could be achieved in 3h. The electrochemical immunosensor was also used to determine E. coli in dairy product (pure fresh milk, infant milk powder, yogurt in shelf-life and expired yogurt), and the recoveries of standard additions were in the range of 96.8-108.7%. Overall, this method gave a useful protocol for E. coli assay with high sensitivity, acceptable accuracy and satisfying stability, and thus provided a powerful tool to estimate the quality of dairy product. PMID:26908184

  13. Design and Evaluation of Tumor-Specific Dendrimer Epigenetic Therapeutics

    Science.gov (United States)

    Zong, Hong; Shah, Dhavan; Selwa, Katherine; Tsuchida, Ryan E; Rattan, Rahul; Mohan, Jay; Stein, Adam B; Otis, James B; Goonewardena, Sascha N

    2015-01-01

    Histone deacetylase inhibitors (HDACi) are promising therapeutics for cancer. HDACi alter the epigenetic state of tumors and provide a unique approach to treat cancer. Although studies with HDACi have shown promise in some cancers, variable efficacy and off-target effects have limited their use. To overcome some of the challenges of traditional HDACi, we sought to use a tumor-specific dendrimer scaffold to deliver HDACi directly to cancer cells. Here we report the design and evaluation of tumor-specific dendrimer–HDACi conjugates. The HDACi was conjugated to the dendrimer using an ester linkage through its hydroxamic acid group, inactivating the HDACi until it is released from the dendrimer. Using a cancer cell model, we demonstrate the functionality of the tumor-specific dendrimer–HDACi conjugates. Furthermore, we demonstrate that unlike traditional HDACi, dendrimer–HDACi conjugates do not affect tumor-associated macrophages, a recently recognized mechanism through which drug resistance emerges. We anticipate that this new class of cell-specific epigenetic therapeutics will have tremendous potential in the treatment of cancer. PMID:26246996

  14. Elasticity of DNA and the effect of Dendrimer Binding

    CERN Document Server

    Mogurampelly, Santosh; Netz, Roland R; Maiti, Prabal K

    2013-01-01

    Negatively charged DNA can be compacted by positively charged dendrimers and the degree of compaction is a delicate balance between the strength of the electrostatic interaction and the elasticity of DNA. We report various elastic properties of short double stranded DNA (dsDNA) and the effect of dendrimer binding using fully atomistic molecular dynamics and numerical simulations. In equilibrium at room temperature, the contour length distribution P(L) and end-to-end distance distribution P(R) are nearly Gaussian, the former gives an estimate of the stretch modulus {\\gamma}_1 of dsDNA in quantitative agreement with the literature value. The bend angle distribution P({\\theta}) of the dsDNA also has a Gaussian form and allows to extract a persistence length, L_p of 43 nm. When the dsDNA is compacted by positively charged dendrimer, the stretch modulus stays invariant but the effective bending rigidity estimated from the end-to-end distance distribution decreases dramatically due to backbone charge neutralization...

  15. Bioreducible cross-linked polymers based on G1 peptide dendrimer as potential gene delivery vectors.

    Science.gov (United States)

    Li, Chun-Yan; Wang, Hai-Jiao; Cao, Jing-Ming; Zhang, Ji; Yu, Xiao-Qi

    2014-11-24

    A series of cationic polymers based on low generation (G1) peptide dendrimer were synthesized with disulfide-containing linkages. The DNA binding abilities of the target polymers were studied by gel electrophoresis and fluorescence quenching assay. The bioreducible property of the disulfide-containing polymers P2 and P3 was also investigated in the presence of dithiothreitol (DTT). Results from dynamic light scattering (DLS) and transmission electron microscopy (TEM) assays reveal that these materials may condense DNA into nanoparticles with proper sizes and zeta-potentials. In vitro cell experiments show that compared to branched 25 KDa PEI, P2 and P3 may exhibit much higher gene transfection efficiency and lower cytotoxicity in both HEK293 and U-2OS cells. Additionally, polymer prepared from Michael addition gives better gene transfection ability, while polymer prepared from ring-opening reaction has better serum tolerance. Results indicate that these polymers might be promising non-viral gene vectors for their easy preparation, very low cytotoxicity, and good transfection efficiency. PMID:25282264

  16. Photo-physical and structural interactions between viologen phosphorus-based dendrimers and human serum albumin

    International Nuclear Information System (INIS)

    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.

  17. Peptide and glycopeptide dendrimer apple trees as enzyme models and for biomedical applications.

    Science.gov (United States)

    Reymond, Jean-Louis; Darbre, Tamis

    2012-02-28

    Solid phase peptide synthesis (SPPS) provides peptides with a dendritic topology when diamino acids are introduced in the sequences. Peptide dendrimers with one to three amino acids between branches can be prepared with up to 38 amino acids (MW ~ 5,000 Da). Larger peptide dendrimers (MW ~ 30,000) were obtained by a multivalent chloroacetyl cysteine (ClAc) ligation. Structural studies of peptide dendrimers by CD, FT-IR, NMR and molecular dynamics reveal molten globule states containing up to 50% of α-helix. Esterase and aldolase peptide dendrimers displaying dendritic effects and enzyme kinetics (k(cat)/k(uncat) ~ 10(5)) were designed or discovered by screening large combinatorial libraries. Strong ligands for Pseudomonas aeruginosa lectins LecA and LecB able to inhibit biofilm formation were obtained with glycopeptide dendrimers. Efficient ligands for cobalamin, cytotoxic colchicine conjugates and antimicrobial peptide dendrimers were also developed showing the versatility of dendritic peptides. Complementing the multivalency, the amino acid composition of the dendrimers strongly influenced the catalytic or biological activity obtained demonstrating the importance of the "apple tree" configuration for protein-like function in peptide dendrimers.

  18. Redox-Controlled Interaction of Biferrocenyl-Terminated Dendrimers with β-Cyclodextrin Molecular Printboards

    NARCIS (Netherlands)

    Nijhuis, Christian A.; Dolatowska, Karolina A.; Ravoo, Bart Jan; Huskens, Jurriaan; Reinhoudt, David N.

    2007-01-01

    This paper describes the synthesis and electrochemistry of biferrocenyl-terminated dendrimers and their β-cyclodextrin (β-CD) inclusion complexes in aqueous solution and at surfaces. Three generations of poly(propylene imine) (PPI) dendrimers, decorated with 4, 8, and 16 biferrocenyl (BFc) units, re

  19. 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. PMID:23415951

  20. Synthesis of poly(amidoamine-dendrimer-silver nanoparticles composite for application as bactericides

    Directory of Open Access Journals (Sweden)

    Shahla Namazkar

    2014-04-01

    Full Text Available As awareness of sanitation, disease transmission factors and personal protection increases, researchers have focused on developing materials with antibacterial properties. Silver-PAMAM-dendrimer has unique antibacterial properties that make it an ideal candidate for medical applications. In this study, poly (amidoamine (PAMAM dendrimers from Generations 0.5- 4.0 were synthesized using divergent methods. Silver was combined with PAMAM dendrimers from the Generation 2.0, 3.0 and 4.0 to form colloidal solutions. The antimicrobial capabilities of Silver-PAMAM-dendrimer (Generation 2.0 were tested against four types of gram positive and negative bacteria. Its bactericidal activities were revealed for all four types of bacteria that could not grow in samples containing 600 ppm of Silver-PAMAM-dendrimer (Generation 2.0.

  1. A new microscopic insight into membrane penetration and reorganization by PETIM dendrimers.

    Science.gov (United States)

    Bhattacharya, R; Kanchi, Subbarao; C, Roobala; Lakshminarayanan, A; Seeck, Oliver H; Maiti, Prabal K; Ayappa, K G; Jayaraman, N; Basu, J K

    2014-10-14

    Dendrimers are highly branched polymeric nanoparticles whose structure and topology, largely, have determined their efficacy in a wide range of studies performed so far. An area of immense interest is their potential as drug and gene delivery vectors. Realizing this potential, depending on the nature of cell surface-dendrimer interactions, here we report controlled model membrane penetration and reorganization, using a model supported lipid bilayer and poly(ether imine) (PETIM) dendrimers of two generations. By systematically varying the areal density of the lipid bilayers, we provide a microscopic insight, through a combination of high resolution scattering, atomic force microscopy and atomistic molecular dynamics simulations, into the mechanism of PETIM dendrimer membrane penetration, pore formation and membrane re-organization induced by such interactions. Our work represents the first systematic observation of a regular barrel-like membrane spanning pore formation by dendrimers, tunable through lipid bilayer packing, without membrane disruption. PMID:25115726

  2. A fluorinated dendrimer achieves excellent gene transfection efficacy at extremely low nitrogen to phosphorus ratios

    Science.gov (United States)

    Wang, Mingming; Liu, Hongmei; Li, Lei; Cheng, Yiyun

    2014-01-01

    Polymers have shown great promise in the design of high efficient and low cytotoxic gene vectors. Here we synthesize fluorinated dendrimers for use as gene vectors. Fluorinated dendrimers achieve excellent gene transfection efficacy in several cell lines (higher than 90% in HEK293 and HeLa cells) at extremely low N/P ratios. These polymers show superior efficacy and biocompatibility compared with several commercial transfection reagents such as Lipofectamine 2000 and SuperFect. Fluorination enhances the cellular uptake of the dendrimer/DNA polyplexes and facilitates their endosomal escape. In addition, the fluorinated dendrimer shows excellent serum resistance and exhibits high gene transfection efficacy even in medium containing 50% FBS. The results suggest that fluorinated dendrimers are a new class of highly efficient gene vectors and fluorination is a promising strategy to design gene vectors without involving sophisticated syntheses.

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

    International Nuclear Information System (INIS)

    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 (1H-NMR, 13C-NMR) and matrix assisted laser desorption/ionization techniques. The synthesized dendrimer presented low dispersion in molecular weights (Mw/Mn = 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 10B-PGLD dendrimer indicate lower cytotoxicity, suggesting that the macromolecule is a biocompatible material. (author)

  4. Dendrimer Phthalocyanine Theranostics for Flourescence Imaging and Photodynamic Therapy of Atheromatous Plagues

    DEFF Research Database (Denmark)

    Ficker, Mario

    carried out in vitro, and in vivo studies are in progress with highly promising initial data. The dendrimer phthalocyanine nanoparticle system was nally chosen by the Consortium of the FP-7 large-scale project CosmoPHOS-nano to be translated into a clinical phase I study in human patients and is currently...... in atherosclerosis, but they cannot remove or stabilize dangerous vulnerable plaques satisfyingly. This thesis describes the development of a theranostic dendrimer-based nanoparticle system for the detection (imaging) of vulnerable atheromatous plaques and their treatment/ stabilization by means of photodynamic...... therapy. For this purpose, a dendrimer nanoparticle system was developed that showed promising cytotoxicity and immunogenicity. These dendrimers were capable of solvating lipophilic phthalocyanines, which are second-generation photosensitizers. The dendrimer phthalocyanine conjugates had light emission...

  5. 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.

  6. Design and physicochemical characterization of poly(amidoamine) nanoparticles and the toxicological evaluation in human endothelial cells: applications to peptide delivery to the brain

    NARCIS (Netherlands)

    Coue, G.M.J.P.C.; Freese, C.; Unger, R.E.; Kirkpatrick, C.J.; Pickl, K.E.; Sinner, F.M.; Engbersen, J.F.J.

    2013-01-01

    In this study, we investigated nanoparticles formulated by self-assembly of a biodegradable poly(amidoamine) (PAA) and a fluorescently labeled peptide, in their capacity to internalize in endothelial cells and deliver the peptide, with possible applications for brain drug delivery. The nanoparticles

  7. Improved Synthesis Strategy of Poly(amidoamine)s for Biomedical Applications: Catalysis by “Green” Biocompatible Earth Alkaline Metal Salts

    NARCIS (Netherlands)

    Zintchenko, Arkadi; Aa, van der Leonardus J.; Engbersen, Johan F.J.

    2011-01-01

    Poly(amidoamine)s (PAAs) have received significant attention due to their good biocompatibility and fast biodegradation profile which gives these polymers high potential in biomedical applications. Conventional synthesis of PAAs via aza-type Michael addition reaction of primary amines to bis-acrylam

  8. Graphene oxide-cationic polymer conjugates: Synthesis and application as gene delivery vectors.

    Science.gov (United States)

    Teimouri, Mohsen; Nia, Azadeh Hashem; Abnous, Khalil; Eshghi, Hossein; Ramezani, Mohammad

    2016-01-01

    Nanomedicine as the interface between nanotechnology and medical sciences is a new area that has attracted the attention of vast groups of researchers. Carbon nanomaterials are common platform for synthesis of nanoparticles for biomedical applications due to their low cytotoxicity and feasible internalization into mammalian cell lines (Yang et al., 2007; Arora et al., 2014; Oh and Park, 2014). Synthesis of vectors based on various cationic polymers polyethylenimine (PEI), polypropylenimine (PPI) and polyamidoamine (PAMAM) and their derivatives were considered as a strategy for transferring plasmid DNA and treatment of genetic diseases. Considering the low cytotoxicity of graphene, chemical modification of its surface has led to fabrication of novel gene delivery systems based on graphene and graphene oxide. Herein we report the synthesis of three groups of vectors based on conjugation of graphene oxide (GO) with alkylated derivatives of three different cationic polymers (polyethylenimine (PEI), polypropylenimine (PPI) and polyamidoamine (PAMAM)) through different linkers including surface carboxyl group, glycine and spermidine. Two main challenges in design of gene delivery vectors is decreasing cytotoxicity while improving the transfection efficiency. All synthesized vectors showed significantly lower cellular toxicity compared to bare polymer. A plasmid encoding green fluorescent protein (GFP) was used to evaluate the transfection efficiency of nanoparticles both qualitatively using live cell fluorescent imaging and quantitatively using flow cytometry and each vector was compared to its polymer base. Most successful conjugation strategy was observed in the case of PEI conjugates among which most efficient vector was PEI-GO conjugate bearing glycine linker. This vector was 9 fold more effective in terms of the percent of EGFP transfected cells. PMID:27072918

  9. 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.

  10. Nanoparticulate platinum films on gold using dendrimer-based wet chemical method

    Indian Academy of Sciences (India)

    S Raghu; Sheela Berchmans; K L N Phani; V Yegnaraman

    2005-11-01

    There is a growing interest in devising wet chemical alternatives for physical deposition methods for applications involving thin films, e.g., catalysis. Deposition of platinum on thin gold films is often a problem leading to incomplete coverage and improper adhesion to solid surfaces. Gold substrates often need pre-activation for achieving complete coverage. We demonstrate here that dendrimers with proper functionalities and size work as well-defined nucleating agents and adhesion promoters. This feature is demonstrated using an amine-terminated dendrimer of generation 4.0. This approach allows one to obtain adherent nanoparticulate films of platinum on gold. Unlike other nucleating agents and adhesion promoting compounds, dendrimers have a well-defined ordered structure in terms of their space filling ability. The stability of the films obtained with adsorbed dendrimers is emonstrated using the electrocatalytic reactions of fuels like methanol. The films formed without dendrimers cannot sustain the electro-oxidation currents due to the instability of the films while the films formed with dendrimers can sustain currents for longer duration and for several cycles. The dendrimer-derived Pt films exhibit higher catalytic activity compared to other methods.

  11. Deswelling and Electrolyte Dissipation in Free Diffusion of Charged PAMAM Dendrimers.

    Science.gov (United States)

    Garcia-Fernandez, Emilio; Paulo, Pedro M R

    2014-04-17

    The diffusion coefficient of charged PAMAM dendrimers was measured by fluorescence correlation spectroscopy in aqueous solution at submicromolar concentrations. The solution pH was varied for conditions ranging from a fully charged to neutral charge dendrimer to infer about electrostatic swelling in the dilute regime. The diffusion coefficient of generation G4 increases by as much as 20% between high and low charge conditions due to the combined effects of polyelectrolyte deswelling and loss of electrolyte dissipation. By taking into account the electrolyte dissipation in the friction factor, we have found that the observed deswelling corresponds to a change of hydrodynamic radius between 7-13% for generation G4 and about 12% for generation G7. Simulations of molecular dynamics of dendrimer G4 show that counterion uptake by the dendrimer structure upon full protonation induces a 16% increase of its radius of gyration. The change in dendrimer size is slightly larger than that previously reported from neutron scattering techniques, thereby suggesting that electrostatic swelling is more pronounced at dilute dendrimer concentration and low ionic strength. It is confirmed that even higher generations, which have more congested molecular structures, can experience some degree of conformational change in response to a change of the dendrimer charge density.

  12. Uptake, efflux, and mass transfer coefficient of fluorescent PAMAM dendrimers into pancreatic cancer cells.

    Science.gov (United States)

    Opitz, Armin W; Czymmek, Kirk J; Wickstrom, Eric; Wagner, Norman J

    2013-02-01

    Targeted delivery of imaging agents to cells can be optimized with the understanding of uptake and efflux rates. Cellular uptake of macromolecules is studied frequently with fluorescent probes. We hypothesized that the internalization and efflux of fluorescently labeled macromolecules into and out of mammalian cells could be quantified by confocal microscopy to determine the rate of uptake and efflux, from which the mass transfer coefficient is calculated. The cellular influx and efflux of a third generation poly(amido amine) (PAMAM) dendrimer labeled with an Alexa Fluor 555 dye was measured in Capan-1 pancreatic cancer cells using confocal fluorescence microscopy. The Capan-1 cells were also labeled with 5-chloromethylfluorescein diacetate (CMFDA) green cell tracker dye to delineate cellular boundaries. A dilution curve of the fluorescently labeled PAMAM dendrimer enabled quantification of the concentration of dendrimer in the cell. A simple mass transfer model described the uptake and efflux behavior of the PAMAM dendrimer. The effective mass transfer coefficient was found to be 0.054±0.043μm/min, which corresponds to a rate constant of 0.035±0.023min(-1) for uptake of the PAMAM dendrimer into the Capan-1 cells. The effective mass transfer coefficient was shown to predict the efflux behavior of the PAMAM dendrimer from the cell if the fraction of labeled dendrimer undergoing non-specific binding is accounted for. This work introduces a novel method to quantify the mass transfer behavior of fluorescently labeled macromolecules into mammalian cells.

  13. Optimization of PAMAM-gold nanoparticle conjugation for gene therapy

    OpenAIRE

    Figueroa, Elizabeth R.; Lin, Adam Y.; Yan, Jiaxi; Luo, Laureen; Foster, Aaron E.; Drezek, Rebekah A.

    2013-01-01

    The development of efficient and biocompatible non-viral vectors for gene therapy remains a great challenge, and exploiting the properties of both nanoparticle carriers and cationic polymers is an attractive approach. In this work, we have developed gold nanoparticle (AuNP) polyamidoamine (PAMAM) conjugates for use as non-viral transfection agents. AuPAMAM conjugates were prepared by crosslinking PAMAM dendrimers to carboxylic-terminated AuNPs via EDC and sulfo-NHS chemistry. EDC and sulfo-NH...

  14. Charge-Dependent Dynamics of Polyelectrolyte Dendrimer and Its Correlation with Invasive Water

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Wei-Ren [ORNL; Hong, Kunlun [ORNL; Li, Xin [ORNL; Liu, Emily [Rensselaer Polytechnic Institute (RPI); Liu, Yun [National Institute of Standards and Technology (NIST); Porcar, L. [National Institute of Standards and Technology (NIST); Smith, Gregory Scott [ORNL; Wu, Bin [ORNL; Mamontov, Eugene [ORNL; Egami, T. [University of Tennessee (UTK) and Oak Ridge National Laboratory (ORNL); Kolesnikov, Alexander I [ORNL; Diallo, Souleymane Omar [Oak Ridge National Laboratory (ORNL)

    2013-01-01

    Atomistic molecular dynamics (MD) simulations were carried out to investigate the local dynamics of polyelectrolyte dendrimers dissolved in deuterium oxide (D2O) and its dependence on molecular charge. Enhanced segmental dy-namics upon increase in molecular charge is observed, consistent with quasielastic neutron scattering (QENS) measurements. A strong coupling between the intra-dendrimer local hydration level and segmental dynamics is also revealed. Compelling evidence shows these findings originate from the electrostatic interaction between the hydrocarbon components of dendrimer and invasive water. This combined study provides fundamental insight into the dynamics of charged polyelectrolytes and the solvating water molecules.

  15. 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 (K......) 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....

  16. Cationic micellar nanoparticles for DNA and doxorubicin co-delivery.

    Science.gov (United States)

    Lin, Jian-Tao; Zou, Ying; Wang, Chao; Zhong, Yue-Chun; Zhao, Yi; Zhu, Hui-Er; Wang, Guan-Hai; Zhang, Li-Ming; Zheng, Xue-Bao

    2014-11-01

    Cationic micellar nanoparticles for chemotherapeutic drugs and therapeutic gene co-delivery were prepared based on a poly-(N-ε-carbobenzyloxy-l-lysine) (PZLL) and dendritic polyamidoamine (PAMAM) block copolymer (PZLL-D3). PZLL-D3 was synthesized by a copper-catalyzed azide alkyne cyclization (click) reaction between α-alkyne-PZLL and azide focal point PAMAM dendrons. Its structure was characterized by (1)H NMR and FTIR, and its buffering capability was determined by acid-base titration. MTT, agarose gel electrophoresis and flow cytometry studies showed that PZLL-D3 revealed low in vitro cytotoxicity, strong pDNA condensation ability, protection of pDNA against deoxyribonuclease I degradation and high gene transfection efficiency in 293T and HeLa cells. In addition, the micellar nanoparticles delivered pDNA and anticancer drug doxorubicin (DOX) simultaneously and efficiently to tumor cells, and the DOX loaded nanoparticles showed sustained in vitro release at pH=7.4 and 5.8. PMID:25280725

  17. 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.

  18. From structure to function via complex supramolecular dendrimer systems.

    Science.gov (United States)

    Sun, Hao-Jan; Zhang, Shaodong; Percec, Virgil

    2015-06-21

    This tutorial review summarizes strategies elaborated for the discovery and prediction of programmed primary structures derived from quasi-equivalent constitutional isomeric libraries of self-assembling dendrons, dendrimers and dendronized polymers. These libraries demonstrate an 82% predictability, defined as the percentage of similar primary structures resulting in at least one conserved supramolecular shape with internal order. A combination of structural and retrostructural analysis that employs methodologies transplanted from structural biology, adapted to giant supramolecular assemblies was used for this process. A periodic table database of programmed primary structures was elaborated and used to facilitate the emergence of a diversity of functions in complex dendrimer systems via first principles. Assemblies generated by supramolecular and covalent polymer backbones were critically compared. Although by definition complex functional systems cannot be designed, this tutorial hints to a methodology based on database analysis principles to facilitate design principles that may help to mediate an accelerated emergence of chemical, physical and most probably also societal, political and economic complex systems on a shorter time scale and lower cost than by the current methods. This tutorial review is limited to the simplest, synthetically most accessible self-assembling minidendrons, minidendrimers and polymers dendronized with minidendrons that are best analyzed and elucidated at molecular, supramolecular and theoretical levels, and most used in other laboratories. These structures are all interrelated, and their principles expand in a simple way to their higher generations. PMID:25325787

  19. Enzyme-linked DNA dendrimer nanosensors for acetylcholine

    Science.gov (United States)

    Walsh, Ryan; Morales, Jennifer M.; Skipwith, Christopher G.; Ruckh, Timothy T.; Clark, Heather A.

    2015-10-01

    It is currently difficult to measure small dynamics of molecules in the brain with high spatial and temporal resolution while connecting them to the bigger picture of brain function. A step towards understanding the underlying neural networks of the brain is the ability to sense discrete changes of acetylcholine within a synapse. Here we show an efficient method for generating acetylcholine-detecting nanosensors based on DNA dendrimer scaffolds that incorporate butyrylcholinesterase and fluorescein in a nanoscale arrangement. These nanosensors are selective for acetylcholine and reversibly respond to levels of acetylcholine in the neurophysiological range. This DNA dendrimer architecture has the potential to overcome current obstacles to sensing in the synaptic environment, including the nanoscale size constraints of the synapse and the ability to quantify the spatio-temporal fluctuations of neurotransmitter release. By combining the control of nanosensor architecture with the strategic placement of fluorescent reporters and enzymes, this novel nanosensor platform can facilitate the development of new selective imaging tools for neuroscience.

  20. Record Multiphoton Absorption Cross-Sections by Dendrimer Organometalation.

    Science.gov (United States)

    Simpson, Peter V; Watson, Laurance A; Barlow, Adam; Wang, Genmiao; Cifuentes, Marie P; Humphrey, Mark G

    2016-02-12

    Large increases in molecular two-photon absorption, the onset of measurable molecular three-photon absorption, and record molecular four-photon absorption in organic π-delocalizable frameworks are achieved by incorporation of bis(diphosphine)ruthenium units with alkynyl linkages. The resultant ruthenium alkynyl-containing dendrimers exhibit strong multiphoton absorption activity through the biological and telecommunications windows in the near-infrared region. The ligated ruthenium units significantly enhance solubility and introduce fully reversible redox switchability to the optical properties. Increasing the ruthenium content leads to substantial increases in multiphoton absorption properties without any loss of optical transparency. This significant improvement in multiphoton absorption performance by incorporation of the organometallic units into the organic π-framework is maintained when the relevant parameters are scaled by molecular weights or number of delocalizable π-electrons. The four-photon absorption cross-section of the most metal-rich dendrimer is an order of magnitude greater than the previous record value. PMID:26797727

  1. Modular degradable dendrimers enable small RNAs to extend survival in an aggressive liver cancer model

    Science.gov (United States)

    Zhou, Kejin; Nguyen, Liem H.; Miller, Jason B.; Yan, Yunfeng; Kos, Petra; Xiong, Hu; Li, Lin; Hao, Jing; Minnig, Jonathan T.; Siegwart, Daniel J.

    2016-01-01

    RNA-based cancer therapies are hindered by the lack of delivery vehicles that avoid cancer-induced organ dysfunction, which exacerbates carrier toxicity. We address this issue by reporting modular degradable dendrimers that achieve the required combination of high potency to tumors and low hepatotoxicity to provide a pronounced survival benefit in an aggressive genetic cancer model. More than 1,500 dendrimers were synthesized using sequential, orthogonal reactions where ester degradability was systematically integrated with chemically diversified cores, peripheries, and generations. A lead dendrimer, 5A2-SC8, provided a broad therapeutic window: identified as potent [EC50 75 mg/kg dendrimer repeated dosing). Delivery of let-7g microRNA (miRNA) mimic inhibited tumor growth and dramatically extended survival. Efficacy stemmed from a combination of a small RNA with the dendrimer’s own negligible toxicity, therefore illuminating an underappreciated complication in treating cancer with RNA-based drugs. PMID:26729861

  2. 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

    2015-09-01

    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.

  3. Catalytic Peptide Dendrimers as Artificial Proteins: Functional Selection and Optimization from Combinatorial Libraries

    Institute of Scientific and Technical Information of China (English)

    Jean-Louis Reymond

    2005-01-01

    @@ 1Introduction In de novo protein design one attempts to create artificial proteins with defined structure and function from first principles, usually with the help of trial-and-error procedures that scan a large number of possible amino acid sequences. Our approach to de novo protein design is based on peptide dendrimers. Dendrimers are tree-like structures that adopt a globular or disk-shaped structure as a consequence of topology rather than folding. Our peptide dendrimers are obtained by alternating alpha-aminoacids with branching diaminoacids[1].Dendrimers containing combinations of histidine, serine and aspartate display enzyme-like catalytic properties for the hydrolysis of esters, including enantiomeric discrimination[1d]. The catalytic effect involves cooperative substrate binding and catalysis by a positive dendritic effect[1d].

  4. Theoretical Investigation of Nonlinear Optical Properties of Organic and Transition Metal Hybrid Azobenzene Dendrimers

    Institute of Scientific and Technical Information of China (English)

    LIU Cai-Ping; LIU Ping; WU Ke-Chen

    2008-01-01

    In this work, we report a theoretical exploration of the responses of organic azo-benzene dendrimers. The polarizabilities, the first and second hyperpolarizabilities of the azobenzene monomers (GO), and the first, second and third generation (G1, G2 and G3, respectively) are investigated by semi-empirical methods. The calculated results show that the nonlinear optical (NLO)properties of these organic dendrimers are mainly determined by the azobenzene chromospheres.Additionally, the values of β and γ increase almost in proportion to the number of chromophores. On the other hand, two types of transition metal hybrid azobenzene dendrimers (core-hybrid and branch-end hybrid according to the sites combined with transition metals) are simulated and discussed in detail in the framework of time-dependent density functional theory (TDDFT). The calculated results reveal that the NLO responses of these metal dendrimers distinctly varied as a result of altering the charge transfer transition scale and the excitation energies.

  5. Converting Nonliquid Crystals into Liquid Crystals by N-Methylation in the Central Linker of Triazine-Based Dendrimers.

    Science.gov (United States)

    Tsai, Meng-Jung; Hsieh, Jei-Way; Lai, Long-Li; Cheng, Kung-Lung; Liu, Shih-Hsien; Lee, Jey-Jau; Hsu, Hsiu-Fu

    2016-06-17

    Two triazine-based dendrimers were successfully prepared in 60-75% yields. These newly prepared dendrimers 2a and 2b containing the -NMe(CH2)2NMe- and the -NMe(CH2)4NMe- linkers between two G3 dendrons, respectively, exhibit columnar phases during the thermal process. However, the corresponding dendrimers 1a and 1b containing the -NH(CH2)2NH- and the -NH(CH2)4NH- linkers between two G3 dendrons, respectively, do not show any LC phases on thermal treatment. Computational investigations on molecular conformations reveal that N-methylation of the dendritic central linker leads dendrimers to possess more isomeric conformations and thus successfully converts non-LC dendrimers (1a and 1b) into LC dendrimers (2a and 2b). PMID:27203100

  6. Polycationic triazine-based dendrimers: effect of peripheral groups on transfection efficiency†

    OpenAIRE

    Mintzer, Meredith A.; Merkel, Olivia M; Kissel, Thomas; Simanek, Eric E

    2009-01-01

    A panel of eight, second generation triazine dendrimers differing in the number of amines, guanidines, hydroxyls and aliphatic groups on the periphery was synthesized and assayed for gene transfer in an attempt to correlate the effects of surface functionality on transfection efficiency. The physicochemical and biological properties of the dendrimers and dendriplexes, such as condensation of DNA, size, surface charge and morphology of dendriplexes, toxicity and ultimately transfection efficie...

  7. Multiscale Modeling for Host-Guest Chemistry of Dendrimers in Solution

    OpenAIRE

    Seung Ha Kim; Lamm, Monica H

    2012-01-01

    Dendrimers have been widely used as nanostructured carriers for guest species in a variety of applications in medicine, catalysis, and environmental remediation. Theory and simulation methods are an important complement to experimental approaches that are designed to develop a fundamental understanding about how dendrimers interact with guest molecules. This review focuses on computational studies aimed at providing a better understanding of the relevant physicochemical parameters at play in ...

  8. The key role of the scaffold on the efficiency of dendrimer nanodrugs

    OpenAIRE

    Caminade, Anne-Marie; Fruchon, Séverine; Turrin, Cédric-Olivier; Poupot, Mary; Ouali, Armelle; Maraval, Alexandrine; Garzoni, Matteo; Maly, Marek; Furer, Victor; Kovalenko, Valeri; Majoral, Jean-Pierre; Pavan, Giovanni M.; Poupot, Rémy

    2015-01-01

    Dendrimers are well-defined macromolecules whose highly branched structure is reminiscent of many natural structures, such as trees, dendritic cells, neurons or the networks of kidneys and lungs. Nature has privileged such branched structures for increasing the efficiency of exchanges with the external medium; thus, the whole structure is of pivotal importance for these natural networks. On the contrary, it is generally believed that the properties of dendrimers are essentially related to the...

  9. The Application of Suzuki Coupling Reaction on the Preparation of Carbosilane Dendrimers with 4-(Naphthalen-1-yl)phenyl Core

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Carbosilane dendrimers with p-bromophenyl core were synthesized by alternating Grignard and hydrosilylation reaction. And the α-naphthalenyl was connected to the core by the Suzuki coupling reaction. A new carbosilane dendrimer with big π-conjugated structure[4-(naphthalen-1-yl)phenyl core] was given. It shows Suzuki coupling reaction is an effective and powerful core-functionalization method and the satisfactory result can be obtained through prolonging the reaction time with the increase of the generation of dendrimer.

  10. 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.

  11. 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

    2016-01-01

    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. PMID:27759006

  12. 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.

  13. 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.

  14. Self-organizing properties of dendrimers and potential applications

    OpenAIRE

    Losson, Myriam; Descheneaux, R; Pugin, R

    2006-01-01

    La nanotechnologie est une science fondamentale et appliquée, à la frontière entre la physique, la chimie, l’ingénierie et les sciences de la vie. Basée sur une approche dite “bottom-up” cette thèse a permis, dans un premier temps, d’étudier la possibilité d’utiliser une matrice de dendrimères commerciaux (PAMAM) afin de promouvoir l’auto-organisation de cyanines en agrégats-J. Parallèlement à cette thématique, nous nous sommes aussi intéressés à l’étude des propriétés d’auto-assemblage de de...

  15. Charge Transport in Dendrimer Melt using Multiscale Modeling Simulation

    CERN Document Server

    Bag, Saientan; Maiti, Prabal K

    2016-01-01

    In this paper we present a theoretical calculation of the charge carrier mobility in two different dendrimeric melt system (Dendritic phenyl azomethine with Triphenyl amine core and Dendritic Carbazole with Cyclic Phenylazomethine as core), which have recently been reported1 to increase the efficiency of Dye-Sensitized solar cells (DSSCs) by interface modification. Our mobility calculation, which is a combination of molecular dynamics simulation, first principles calculation and kinetic Monte Carlo simulation, leads to mobilities that are in quantitative agreement with available experimental data. We also show how the mobility depends on the dendrimer generation. Furthermore, we examine the variation of mobility with external electric field and external reorganization energy. Physical mechanisms behind observed electric field and generation dependencies of mobility are also explored.

  16. Dendrimer light-harvesting: intramolecular electrodynamics and mechanisms.

    Science.gov (United States)

    Andrews, David L; Bradshaw, David S; Jenkins, Robert D; Rodríguez, Justo

    2009-12-01

    In the development of highly efficient materials for harvesting solar energy, there is an increasing focus on purpose-built dendrimers and allied multi-chromophore systems. A proliferation of antenna chromophores is not the only factor determining the sought light-harvesting efficiency; the internal geometry and photophysics of these molecules are also crucially important. In particular, the mechanisms by means of which radiant energy is ultimately trapped depends on an intricate interplay of electronic, structural, energetic and symmetry properties. To better understand these processes a sound theoretical representation of the intramolecular electrodynamics is required. A suitable formalism, based on quantum electrodynamics, readily delivers physical insights into the necessary excitation channelling processes, and it affords a rigorous basis for modelling the intramolecular flow of energy.

  17. 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

  18. Use of carbosilane dendrimer to switch macrophage polarization for the acquisition of antitumor functions

    Science.gov (United States)

    Perisé-Barrios, Ana J.; Gómez, Rafael; Corbí, Angel L.; de La Mata, Javier; Domínguez-Soto, Angeles; Muñoz-Fernandez, María A.

    2015-02-01

    Tumor microenvironment favors the escape from immunosurveillance by promoting immunosuppression and blunting pro-inflammatory responses. Since most tumor-associated macrophages (TAM) exhibit an M2-like tumor cell growth promoting polarization, we have studied the role of 2G-03NN24 carbosilane dendrimer in M2 macrophage polarization to evaluate the potential application of dendrimers in tumor immunotherapy. We found that the 2G-03NN24 dendrimer decreases LPS-induced IL-10 production from in vitro generated monocyte-derived M2 macrophages, and also switches their gene expression profile towards the acquisition of M1 polarization markers (INHBA, SERPINE1, FLT1, EGLN3 and ALDH1A2) and the loss of M2 polarization-associated markers (EMR1, IGF1, FOLR2 and SLC40A1). Furthermore, 2G-03NN24 dendrimer decreases STAT3 activation. Our results indicate that the 2G-03NN24 dendrimer can be a useful tool for antitumor therapy by virtue of its potential ability to limit the M2-like polarization of TAM.Tumor microenvironment favors the escape from immunosurveillance by promoting immunosuppression and blunting pro-inflammatory responses. Since most tumor-associated macrophages (TAM) exhibit an M2-like tumor cell growth promoting polarization, we have studied the role of 2G-03NN24 carbosilane dendrimer in M2 macrophage polarization to evaluate the potential application of dendrimers in tumor immunotherapy. We found that the 2G-03NN24 dendrimer decreases LPS-induced IL-10 production from in vitro generated monocyte-derived M2 macrophages, and also switches their gene expression profile towards the acquisition of M1 polarization markers (INHBA, SERPINE1, FLT1, EGLN3 and ALDH1A2) and the loss of M2 polarization-associated markers (EMR1, IGF1, FOLR2 and SLC40A1). Furthermore, 2G-03NN24 dendrimer decreases STAT3 activation. Our results indicate that the 2G-03NN24 dendrimer can be a useful tool for antitumor therapy by virtue of its potential ability to limit the M2-like polarization of TAM

  19. Dendrisomes: vesicular structures derived from a cationic lipidic dendron.

    Science.gov (United States)

    Al-Jamal, Khuloud T; Sakthivel, Thiagarajan; Florence, Alexander T

    2005-01-01

    The behavior of a novel synthetic lipidic cationic lysine-based dendron (partial dendrimer) in aqueous media and its ability, with and without cholesterol, to self-assemble into higher order structures was studied to gain an understanding of these structures as potential drug carriers. The dendron was prepared by solid-phase peptide synthesis. A reverse-phase evaporation (REV) technique was used to prepare cationic vesicular aggregates of the dendron with different molar ratios of cholesterol. The size and zeta potential of these supramolecular aggregates or "dendrisomes" was determined by photon correlation spectroscopy (PCS). Dendrisome morphology and thermotropic properties were studied by transmission electron microscopy (TEM) and differential scanning calorimetry (DSC). Radiolabeled penicillin G was used as a model of a negatively charged water-soluble compound to investigate the encapsulation efficiency of the dendrisomes. In vitro release of the drug was determined using as a comparator a REV liposome formulation. Dendrisomes of all compositions have higher encapsulation efficiencies and slower release rates compared to the comparator. Cholesterol was found both to increase the size of the aggregates from around 310 to 560 nm and to increase shape irregularities, but did not change the positive zeta potential, in the order of +50 mV, of the dendrisomes. Cholesterol decreases penicillin G entrapment efficiency but increases solute leakage at 25 degrees C. PMID:15761934

  20. Synthesis and evaluation in vitro in cancer cells AR42J of the radiopharmaceutical {sup 99m}Tc-Tyr{sup 3}-Octreotide-dendrimer similar of somatostatin; Sintesis y evaluacion in vitro en celulas de cancer AR42J del radiofarmaco {sup 99m}Tc-Tyr{sup 3}-Octreotido-dendrimero analogo de la somatostatina

    Energy Technology Data Exchange (ETDEWEB)

    Orocio R, E.

    2013-07-01

    The objective of this project was preparing a multimeric system through the conjugation of several molecules of the peptide Tyr{sup 3}-Octreotide to a dendrimer molecule based on Poly-amidoamine (PAMAM), as well as radiolabeled with {sup 99m}Tc and evaluating its behavior like new radiopharmaceutical similar of somatostatin. The dendrimer PAMAM generation 3.5 that possesses terminal groups of sodium carboxylate, was functionalized to peptide Tyr{sup 3}-Octreotide through a reaction of peptide coupling with HATU (hexafluorophosphate (V) of 1-oxide-3-(bis(dimethylamino)methylene)-3H-[1,2,3]triazole[4,5-b]pyridine) as activating agent of carboxylate groups using the Size Exclusion Chromatography (Sec) as purification method. The product was characterized by Ultraviolet visible spectrophotometry, Mid-infrared and Far-infrared, Elemental analysis, Energy dispersive X-ray spectroscopy, Scanning electron microscopy, Thermogravimetry and Differential scanning calorimetry. The radiolabeled with {sup 99m}Tc was carried out using a direct method that involves the reduction of the anion TcO{sub 4}{sup -} with stannous chloride, so that the dendrimer is capable of coordinating to the technetium forming a chelate compound. The radiochemical purity of the radiolabeled compound was determined by thin layer chromatography using a sodium chloride solution to 20% (m/v) as mobile phase and was verified by molecular exclusion chromatography. The radiolabeled compound was possible to obtain it with a radiochemical purity superior to 90%. Also, the specific and not specific union was evaluated of the synthesized compound in mouse pancreas cancer cells AR42J, positive to somatostatin receptors, showing specific recognition for this receptors type with high cellular internalization. The biodistribution studies were carried out in BALB/c mice at different post injection times and in nude mice with induced tumors AR42J. The results showed that the {sup 99m}Tc-PAMAM-Tyr{sup 3}-Octreotide is

  1. Selective synthesis of Rh5 carbonyl clusters within a polyamine dendrimer for chemoselective reduction of nitro aromatics.

    Science.gov (United States)

    Maeno, Zen; Mitsudome, Takato; Mizugaki, Tomoo; Jitsukawa, Koichiro; Kaneda, Kiyotomi

    2014-06-21

    The selective synthesis of the [Rh5(CO)15](-) cluster within the PPI dendrimer was successfully demonstrated. The dendrimer-encapsulated [Rh5(CO)15](-) was resistant to decomposition under the catalytic reaction conditions and exhibited extremely high selectivity for the chemoselective reduction of nitro groups of various nitro aromatics with other reducible groups using CO/H2O as a reductant.

  2. Phenylboronic acid-functionalized polyamidoamine-mediated Bcl-2 siRNA delivery for inhibiting the cell proliferation.

    Science.gov (United States)

    Wu, Di; Yang, Jiebing; Xing, Zhen; Han, Haobo; Wang, Tingting; Zhang, Aijun; Yang, Yan; Li, Quanshun

    2016-10-01

    In this study, the conjugation of phenylboronic acid (PBA) to amine-terminated polyamidoamine (PAMAM) was successfully conducted to prepare a tumor-targeted gene carrier PBA-functionalized PAMAM (PPP) for Bcl-2 siRNA delivery, using a heterobifunctional crosslinker NHS-PEG5k-Mal. The carrier possessed favorable capacity for siRNA condensation and could protect siRNA from the degradation against RNase and serum. The introduction of PBA could facilitate the cellular uptake and further transfection of Bcl-2 siRNA demonstrated by confocal laser scanning microscopy and flow cytometry. Meanwhile, PPP-mediated transfection of Bcl-2 siRNA could significantly inhibit the expression of Bcl-2 gene at both mRNA and protein levels. Furthermore, owing to the knock-down of Bcl-2, PPP/siRNA could significantly inhibit the cell proliferation by inducing the cell apoptosis, and also enhance the antitumor efficiency of doxorubicin by suppressing the resistance of tumor cells to chemotherapeutics. In conclusion, the PPP-mediated Bcl-2 siRNA delivery could potentially be an effective platform for solving the drug resistance and further achieving the combined chemotherapy and gene therapy in tumor treatment. PMID:27371891

  3. Anti-angiogenesis effect of generation 4 polyamidoamine/vascular endothelial growth factor antisense oligodeoxynucleotide on breast cancer in vitro

    Institute of Scientific and Technical Information of China (English)

    Shan-zhi GU; Xin-han ZHAO; Ling-xiao ZHANG; Li LI; Zhi-yu WANG; Min MENG; Gai-li AN

    2009-01-01

    Objective: To study the effects of the generation 4 polyamidoamine/vascular endothelial growth factor antisense oligodeoxynucleotide (G4PAMAMNEGFASODN) compound on the expressions of vascular endothelial growth factor (VEGF) and its mRNA of breast cancer cells and on the inhibition of vascular endothelial cells. Methods: We examined the morphology of G4PAMAM/VEGFASODN compound and its pH stability, in vitro transfection efficiency and toxicity, and the expressions of VEGF and its mRNA. Methyl thiazolyl tetrazolium assay was used to detect the inhibitory function of the compound on vascular endothelial cells. Results: The compound was about 10 nm in diameter and was homogeneously netlike. From pH 5 to 10, it showed quite a buffered ability. The 48-h transfection rate in the charge ratio of 1:40 was 98.76%, significantly higher than that of the liposome group (P<0.05). None of the transfection products showed obvious toxicity on the cells. The expressions of both VEGF protein and its mRNA after G4PAMAM/VEGFASODN transfection decreased markedly. Conclusion: With a low toxicity, high safety, and high transfection rate, G4PAMAMNEGFASODN could be a promising gene vector. Specifically, it inhibits VEGF gene expression efficiently, laying a basis for further in vivo animal studies.

  4. Methotrexate Nanoparticles Prepared with Codendrimer from Polyamidoamine (PAMAM) and Oligoethylene Glycols (OEG) Dendrons: Antitumor Efficacy in Vitro and in Vivo.

    Science.gov (United States)

    Zhao, Yanna; Guo, Yifei; Li, Ran; Wang, Ting; Han, Meihua; Zhu, Chunyan; Wang, Xiangtao

    2016-01-01

    The novel methotrexate-loaded nanoparticles (MTX/PGD NPs) prepared with amphiphilic codendrimer PGD from polyamidoamine and oligothylene glycol dendrons were obtained via antisolvent precipitation method augmented by ultrasonication. Based on the excellent hydrophility of PGD, the drug-loaded nanoparticles could be investigated easily with the high drug-loading content (~85.2%, w/w). The MTX/PGD NPs possessed spherical morphology, nanoscaled particle size (approximately 182.4 nm), and narrow particle size distribution. Release of MTX from MTX/PGD NPs showed a sustained release manner and completed within 48 h. Hemolytic evaluation indicated MTX/PGD NPs presented good blood compatibility, and the cytotoxicity of nanoparticles against breast cancer cells in vitro, biodistribution in tumor tissue, and antitumor efficacy in vivo were enhanced significantly compared to MTX injection. According to the higher drug-loading content, enhanced antitumor efficacy, and appropriate particle size, MTX/PGD NPs as the drug delivery systems could have potential application for cancer chemotherapy in clinic. PMID:27388443

  5. Methotrexate Nanoparticles Prepared with Codendrimer from Polyamidoamine (PAMAM) and Oligoethylene Glycols (OEG) Dendrons: Antitumor Efficacy in Vitro and in Vivo

    Science.gov (United States)

    Zhao, Yanna; Guo, Yifei; Li, Ran; Wang, Ting; Han, Meihua; Zhu, Chunyan; Wang, Xiangtao

    2016-07-01

    The novel methotrexate-loaded nanoparticles (MTX/PGD NPs) prepared with amphiphilic codendrimer PGD from polyamidoamine and oligothylene glycol dendrons were obtained via antisolvent precipitation method augmented by ultrasonication. Based on the excellent hydrophility of PGD, the drug-loaded nanoparticles could be investigated easily with the high drug-loading content (~85.2%, w/w). The MTX/PGD NPs possessed spherical morphology, nanoscaled particle size (approximately 182.4 nm), and narrow particle size distribution. Release of MTX from MTX/PGD NPs showed a sustained release manner and completed within 48 h. Hemolytic evaluation indicated MTX/PGD NPs presented good blood compatibility, and the cytotoxicity of nanoparticles against breast cancer cells in vitro, biodistribution in tumor tissue, and antitumor efficacy in vivo were enhanced significantly compared to MTX injection. According to the higher drug-loading content, enhanced antitumor efficacy, and appropriate particle size, MTX/PGD NPs as the drug delivery systems could have potential application for cancer chemotherapy in clinic.

  6. 羧基封端的树枝状聚酰胺-胺的制备及其与铬盐的配位作用%Preparation of Polyamidoamine Dendrimers End Capped with Carboxyl and Coordination with Chrome Salt

    Institute of Scientific and Technical Information of China (English)

    范贵洋; 靳丽强; 李彦春; 于永昌; 梁志新

    2008-01-01

    以乙二胺和丙烯酸甲酯为原料,通过反复进行迈克尔加成反应和酰胺化反应,得到0.5~3.5代树枝状PAM.AM.利用红外光谱和核磁共振对其结构进行了确认和表征.在酸性条件下,将半代PAMAM水解得到端基为羧基的PAMAM-COOH.胶体电荷滴定表明:PAMAM-COOH具有两性聚合物的特征,其水溶性与溶液的pH值无关.利用紫外可见光谱和浊度法研究了PAMAM-COOH与铬盐的配位作用.结果证实PAMAM-COOH可以与铬盐形成大分子金属配合物;铬盐与PAMAM-COOH配位后,其耐碱能力增加.并对大分子金属配合物的分子构型进行了模拟.

  7. Intracellular trafficking of polyamidoamine-poly(ethylene glycol) block copolymers in DNA delivery.

    Science.gov (United States)

    Bonner, Daniel K; Leung, Cheuk; Chen-Liang, Jane; Chingozha, Loice; Langer, Robert; Hammond, Paula T

    2011-08-17

    The delivery of nucleic acids has the potential to revolutionize medicine by allowing previously untreatable diseases to be clinically addressed. Viral delivery systems have shown immunogenicity and toxicity dangers, but synthetic vectors have lagged in transfection efficiency. Previously, we developed a modular, linear-dendritic block copolymer architecture with high gene transfection efficiency compared to commercial standards. This rationally designed system makes use of a cationic dendritic block to condense the anionic DNA and forms complexes with favorable endosomal escape properties. The linear block provides biocompatibility and protection from serum proteins, and can be functionalized with a targeting ligand. In this work, we quantitate performance of this system with respect to intracellular barriers to gene delivery using both high-throughput and traditional approaches. An image-based, high-throughput assay for endosomal escape is described and applied to the block copolymer system. Nuclear entry is demonstrated to be the most significant barrier to more efficient delivery and will be addressed in future versions of the system.

  8. Dendrimer-Encapsulated Ruthenium Nanoparticles as Catalysts for Lithium-O2 Batteries

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharya, Priyanka; Nasybulin, Eduard N.; Engelhard, Mark H.; Kovarik, Libor; Bowden, Mark E.; Li, Shari; Gaspar, Daniel J.; Xu, Wu; Zhang, Jiguang

    2014-12-01

    Dendrimer-encapsulated ruthenium nanoparticles (DEN-Ru) have been used as catalysts in lithium-O2 batteries for the first time. Results obtained from UV-vis spectroscopy, electron microscopy and X-ray photoelectron spectroscopy show that the nanoparticles synthesized by the dendrimer template method are ruthenium oxide instead of metallic ruthenium reported earlier by other groups. The DEN-Ru significantly improve the cycling stability of lithium (Li)-O2 batteries with carbon black electrodes and decrease the charging potential even at low catalyst loading. The monodispersity, porosity and large number of surface functionalities of the dendrimer template prevent the aggregation of the ruthenium nanoparticles making their entire surface area available for catalysis. The potential of using DEN-Ru as stand-alone cathode materials for Li-O2 batteries is also explored.

  9. Elucidation of the interaction mechanism with liposomes of gH625-peptide functionalized dendrimers.

    Directory of Open Access Journals (Sweden)

    Annarita Falanga

    Full Text Available 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.

  10. 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.

  11. Thermal stability of second generation carbosilane dendrimers with peripheral ammonia groups

    Energy Technology Data Exchange (ETDEWEB)

    Popescu, Maria-Cristina, E-mail: cpopescu@icmpp.ro [' Petru Poni' Institute of Macromolecular Chemistry of Romanian Academy (Romania); Gomez, Rafael; Mata, Fco Javier de la; Rasines, Beatriz [Campus Universitario, Universidad de Alcala, Dpto. de Quimica Inorganica (Spain); Simionescu, Bogdan C. [' Petru Poni' Institute of Macromolecular Chemistry of Romanian Academy (Romania)

    2013-10-15

    Thermal analysis has a wide range of applications in pharmaceutical industry, in designing new molecules, control of raw materials, stability, compatibility studies, and development of new formulations. This paper evaluates the thermodynamic properties of two second generation G2 carbosilane dendrimers with peripheral ammonia groups by differential scanning calorimetry and TG/FTIR coupled techniques. The physical transformations have been detected and their thermodynamic characteristics have been estimated and analyzed. Both dendrimers are stable up to 150 Degree-Sign C, have the Tg at 75 and 59 Degree-Sign C and melting temperatures at 113 and 128 Degree-Sign C, respectively. The decomposition process proved to be very complex and takes place in three steps in nitrogen atmosphere and four steps in air, for both types of dendrimers. IR spectroscopic analysis was used to observe the evolution of the gaseous products versus temperature.

  12. Synthesis of an amphiphilic dendrimer-like block copolymer and its application on drug delivery

    KAUST Repository

    Wang, Shuaipeng

    2014-10-27

    Dendrimer-like amphiphilic copolymer is a kind of three-dimensional spherical structure polymer. An amphiphilic dendrimer-like diblock copolymer, PEEGE-G2-b-PEO(OH)12, constituted of a hydrophobic poly(ethoxyethyl glycidol ether) inner core and a hydrophilic poly(ethylene oxide) outer layer, has been successfully synthesized by the living anionic ring-opening polymerization method. The intermediates and targeted products were characterized with 1H NMR spectroscopy and gel permeation chromatography. The application on drug delivery of dendrimer-like diblock copolymer PEEGE-G2-b-PEO(OH)12 using DOX as a model drug was also studied. The drug loading content and encapsulation efficiency were found at 13.07% and 45.75%, respectively. In vitro release experiment results indicated that the drug-loaded micelles exhibited a sustained release behavior under acidic media.

  13. The key role of the scaffold on the efficiency of dendrimer nanodrugs.

    Science.gov (United States)

    Caminade, Anne-Marie; Fruchon, Séverine; Turrin, Cédric-Olivier; Poupot, Mary; Ouali, Armelle; Maraval, Alexandrine; Garzoni, Matteo; Maly, Marek; Furer, Victor; Kovalenko, Valeri; Majoral, Jean-Pierre; Pavan, Giovanni M; Poupot, Rémy

    2015-01-01

    Dendrimers are well-defined macromolecules whose highly branched structure is reminiscent of many natural structures, such as trees, dendritic cells, neurons or the networks of kidneys and lungs. Nature has privileged such branched structures for increasing the efficiency of exchanges with the external medium; thus, the whole structure is of pivotal importance for these natural networks. On the contrary, it is generally believed that the properties of dendrimers are essentially related to their terminal groups, and that the internal structure plays the minor role of an 'innocent' scaffold. Here we show that such an assertion is misleading, using convergent information from biological data (human monocytes activation) and all-atom molecular dynamics simulations on seven families of dendrimers (13 compounds) that we have synthesized, possessing identical terminal groups, but different internal structures. This work demonstrates that the scaffold of nanodrugs strongly influences their properties, somewhat reminiscent of the backbone of proteins. PMID:26169490

  14. Visualizing the Needle in the Haystack: In Situ Hybridization With Fluorescent Dendrimers

    Directory of Open Access Journals (Sweden)

    Gerhart Jacquelyn

    2004-01-01

    Full Text Available In situ hybridization with 3DNA™ dendrimers is a novel tool for detecting low levels of mRNA in tissue sections and whole embryos. Fluorescently labeled dendrimers were used to identify cells that express mRNA for the skeletal muscle transcription factor MyoD in the early chick embryo. A small population of MyoD mRNA positive cells was found in the epiblast prior to the initiation of gastrulation, two days earlier than previously detected using enzymatic or radiolabeled probes for mRNA. When isolated from the epiblast and placed in culture, the MyoD mRNA positive cells were able to differentiate into skeletal muscle cells. These results demonstrate that DNA dendrimers are sensitive and precise tools for identifying low levels of mRNA in single cells and tissues.

  15. Dendrimer-like hybrid particles with tunable hierarchical pores

    Science.gov (United States)

    Du, Xin; Li, Xiaoyu; Huang, Hongwei; He, Junhui; Zhang, Xueji

    2015-03-01

    Dendrimer-like silica particles with a center-radial dendritic framework and a synergistic hierarchical porosity have attracted much attention due to their unique open three-dimensional superstructures with high accessibility to the internal surface areas; however, the delicate regulation of the hierarchical porosity has been difficult to achieve up to now. Herein, a series of dendrimer-like amino-functionalized silica particles with tunable hierarchical pores (HPSNs-NH2) were successfully fabricated by carefully regulating and optimizing the various experimental parameters in the ethyl ether emulsion systems via a one-pot sol-gel reaction. Interestingly, the simple adjustment of the stirring rate or reaction temperature was found to be an easy and effective route to achieve the controllable regulation towards center-radial large pore sizes from ca. 37-267 (148 +/- 45) nm to ca. 8-119 (36 +/- 21) nm for HPSNs-NH2 with particle sizes of 300-700 nm and from ca. 9-157 (52 +/- 28) nm to ca. 8-105 (30 +/- 16) nm for HPSNs-NH2 with particle sizes of 100-320 nm. To the best of our knowledge, this is the first successful regulation towards center-radial large pore sizes in such large ranges. The formation of HPSNs-NH2 may be attributed to the complex cross-coupling of two processes: the dynamic diffusion of ethyl ether molecules and the self-assembly of partially hydrolyzed TEOS species and CTAB molecules at the dynamic ethyl ether-water interface of uniform small quasi-emulsion droplets. Thus, these results regarding the elaborate regulation of center-radial large pores and particle sizes not only help us better understand the complicated self-assembly at the dynamic oil-water interface, but also provide a unique and ideal platform as carriers or supports for adsorption, separation, catalysis, biomedicine, and sensor.Dendrimer-like silica particles with a center-radial dendritic framework and a synergistic hierarchical porosity have attracted much attention due to their

  16. Structure activity relationship of dendrimer microbicides with dual action antiviral activity.

    Directory of Open Access Journals (Sweden)

    David Tyssen

    Full Text Available BACKGROUND: Topical microbicides, used by women to prevent the transmission of HIV and other sexually transmitted infections are urgently required. Dendrimers are highly branched nanoparticles being developed as microbicides. However, the anti-HIV and HSV structure-activity relationship of dendrimers comprising benzyhydryl amide cores and lysine branches, and a comprehensive analysis of their broad-spectrum anti-HIV activity and mechanism of action have not been published. METHODS AND FINDINGS: Dendrimers with optimized activity against HIV-1 and HSV-2 were identified with respect to the number of lysine branches (generations and surface groups. Antiviral activity was determined in cell culture assays. Time-of-addition assays were performed to determine dendrimer mechanism of action. In vivo toxicity and HSV-2 inhibitory activity were evaluated in the mouse HSV-2 susceptibility model. Surface groups imparting the most potent inhibitory activity against HIV-1 and HSV-2 were naphthalene disulfonic acid (DNAA and 3,5-disulfobenzoic acid exhibiting the greatest anionic charge and hydrophobicity of the seven surface groups tested. Their anti-HIV-1 activity did not appreciably increase beyond a second-generation dendrimer while dendrimers larger than two generations were required for potent anti-HSV-2 activity. Second (SPL7115 and fourth generation (SPL7013 DNAA dendrimers demonstrated broad-spectrum anti-HIV activity. However, SPL7013 was more active against HSV and blocking HIV-1 envelope mediated cell-to-cell fusion. SPL7013 and SPL7115 inhibited viral entry with similar potency against CXCR4-(X4 and CCR5-using (R5 HIV-1 strains. SPL7013 was not toxic and provided at least 12 h protection against HSV-2 in the mouse vagina. CONCLUSIONS: Dendrimers can be engineered with optimized potency against HIV and HSV representing a unique platform for the controlled synthesis of chemically defined multivalent agents as viral entry inhibitors. SPL7013 is

  17. History, Classification, Molecular Structure and Properties of Dendrimers which are a New Concept in Textile

    Directory of Open Access Journals (Sweden)

    Osman NAMIRTI

    2011-02-01

    Full Text Available Over the last 20 years polymer chemistry has created a number of non-lineer structures and introduction of a large number of branches during the polymer synthesis leads to obtain molecules with many end groups. Two types of these polymers are regularly branched "dendrimers" and "hyperbranched polymers" where branching is formed randomly. In this article knowledge about history, classification, molecular structure and properties of dendrimers which have found various application areas also in textile due to their special structures is given.

  18. Dendrimers destabilize proteins in a generation-dependent manner involving electrostatic interactions

    DEFF Research Database (Denmark)

    Gichm, Lise; Christensen, Casper; Boas, Ulrik;

    2008-01-01

    . Destabilization is markedly generation-dependent and is most pronounced for generation 3, which is also the most efficient at precipitating insulin. This suggests that proteins can interact with both dendrimer sui-face and interior. The pH-dependence reveals that interactions are mainly mediated by electrostatics......, but their mode of action is unclear. We show that poly(propylene imine) dendrimers based on di-aminobutane (DAB) and modified with guanidinium surface groups reduce insulin thermostability and solubility considerably at microgram per microliter concentrations, while urea-modified groups have hardly any effect...

  19. Gadolinium MRI Contrast Agents Based on Triazine Dendrimers: Relaxivity and In Vivo Pharmacokinetics

    OpenAIRE

    Lim, Jongdoo; Turkbey, Baris; Bernardo, Marcelino; Bryant, L. Henry; Garzoni, Matteo; Pavan, Giovanni M.; Nakajima, Takahito; Choyke, Peter L; Simanek, Eric E; Kobayashi, Hisataka

    2012-01-01

    Four gadolinium (Gd)-based macromolecular contrast agents, G3-(Gd-DOTA)24, G5-(Gd-DOTA)96, G3-(Gd-DTPA)24, and G5-(Gd-DTPA)96, were prepared that varied in the size of dendrimer (generation three and five), the type of chelate group (DTPA or DOTA), and the theoretical number of metallated chelates (24 and 96). Synthesis relied on a dichlorotriazine derivatized with a DOTA or DTPA ligand that was incorporated into the dendrimer and ultimately metallated with Gd ions. Paramagnetic characteristi...

  20. Facile preparation of highly luminescent CdTe quantum dots within hyperbranched poly(amidoamine)s and their application in bio-imaging

    OpenAIRE

    Shi, Yunfeng; Liu, Lin; Pang, Huan; Zhou, Hongli; Zhang, Guanqing; Ou, Yangyan; Zhang, Xiaoyin; Du, Jimin; Xiao, Wangchuan

    2014-01-01

    A new strategy for facile preparation of highly luminescent CdTe quantum dots (QDs) within amine-terminated hyperbranched poly(amidoamine)s (HPAMAM) was proposed in this paper. CdTe precursors were first prepared by adding NaHTe to aqueous Cd2+ chelated by 3-mercaptopropionic sodium (MPA-Na), and then HPAMAM was introduced to stabilize the CdTe precursors. After microwave irradiation, highly fluorescent and stable CdTe QDs stabilized by MPA-Na and HPAMAM were obtained. The CdTe QDs showed a h...

  1. X-ray computed tomography contrast agents prepared by seeded growth of gold nanoparticles in PEGylated dendrimer

    Energy Technology Data Exchange (ETDEWEB)

    Kojima, Chie [Nanoscience and Nanotechnology Research Center, Research Organization for the 21st Century, Osaka Prefecture University, 1-2 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8570 (Japan); Umeda, Yasuhito; Harada, Atsushi; Kono, Kenji [Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531 (Japan); Ogawa, Mikako; Magata, Yasuhiro, E-mail: c-kojima@21c.osakafu-u.ac.jp [Photon Medical Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192 (Japan)

    2010-06-18

    Gold nanoparticles (Au NPs) are a potential x-ray computed tomography (CT) contrast agent. A biocompatible and bioinactive surface is necessary for application of gold nanoparticle to CT imaging. Polyethylene glycol (PEG)-attached dendrimers have been used as a drug carrier with long blood circulation. In this study, the Au NPs were grown in the PEGylated dendrimer to produce a CT contrast agent. The Au NPs were grown by adding gold ions and ascorbic acid at various equivalents to the Au NP-encapsulated dendrimer solution. Both size and surface plasmon absorption of the grown Au NPs increased with adding a large number of gold ions. The x-ray attenuation of the Au NPs also increased after the seeded growth. The Au NPs grown in the PEG-attached dendrimer at the maximum under our conditions exhibited a similar CT value to a commercial iodine agent, iopamidol, in vitro. The Au NP-loaded PEGylated dendrimer and iopamidol were injected into mice and CT images were obtained at different times. The Au NP-loaded PEGylated dendrimer achieved a blood pool imaging, which was greater than a commercial iodine agent. Even though iopamidol was excreted rapidly, the PEGylated dendrimer loading the grown Au NP was accumulated in the liver.

  2. X-ray computed tomography contrast agents prepared by seeded growth of gold nanoparticles in PEGylated dendrimer

    Science.gov (United States)

    Kojima, Chie; Umeda, Yasuhito; Ogawa, Mikako; Harada, Atsushi; Magata, Yasuhiro; Kono, Kenji

    2010-06-01

    Gold nanoparticles (Au NPs) are a potential x-ray computed tomography (CT) contrast agent. A biocompatible and bioinactive surface is necessary for application of gold nanoparticle to CT imaging. Polyethylene glycol (PEG)-attached dendrimers have been used as a drug carrier with long blood circulation. In this study, the Au NPs were grown in the PEGylated dendrimer to produce a CT contrast agent. The Au NPs were grown by adding gold ions and ascorbic acid at various equivalents to the Au NP-encapsulated dendrimer solution. Both size and surface plasmon absorption of the grown Au NPs increased with adding a large number of gold ions. The x-ray attenuation of the Au NPs also increased after the seeded growth. The Au NPs grown in the PEG-attached dendrimer at the maximum under our conditions exhibited a similar CT value to a commercial iodine agent, iopamidol, in vitro. The Au NP-loaded PEGylated dendrimer and iopamidol were injected into mice and CT images were obtained at different times. The Au NP-loaded PEGylated dendrimer achieved a blood pool imaging, which was greater than a commercial iodine agent. Even though iopamidol was excreted rapidly, the PEGylated dendrimer loading the grown Au NP was accumulated in the liver.

  3. Multivalency effects on Pseudomonas aeruginosa biofilm inhibition and dispersal by glycopeptide dendrimers targeting lectin LecA.

    Science.gov (United States)

    Bergmann, Myriam; Michaud, Gaëlle; Visini, Ricardo; Jin, Xian; Gillon, Emilie; Stocker, Achim; Imberty, Anne; Darbre, Tamis; Reymond, Jean-Louis

    2016-01-01

    The galactose specific lectin LecA partly mediates the formation of antibiotic resistant biofilms by Pseudomonas aeruginosa, an opportunistic pathogen causing lethal airways infections in immunocompromised and cystic fibrosis patients, suggesting that preventing LecA binding to natural saccharides might provide new opportunities for treatment. Here 8-fold (G3) and 16-fold (G4) galactosylated analogs of GalAG2, a tetravalent G2 glycopeptide dendrimer LecA ligand and P. aeruginosa biofilm inhibitor, were obtained by convergent chloroacetyl thioether (ClAc) ligation between 4-fold or 8-fold chloroacetylated dendrimer cores and digalactosylated dendritic arms. Hemagglutination inhibition, isothermal titration calorimetry and biofilm inhibition assays showed that G3 dendrimers bind LecA slightly better than their parent G2 dendrimers and induce complete biofilm inhibition and dispersal of P. aeruginosa biofilms, while G4 dendrimers show reduced binding and no biofilm inhibition. A binding model accounting for the observed saturation of glycopeptide dendrimer galactosyl groups and LecA binding sites is proposed based on the crystal structure of a G3 dendrimer LecA complex.

  4. Expanding the structural diversity of self-assembling dendrons and supramolecular dendrimers via complex building blocks.

    Science.gov (United States)

    Percec, Virgil; Won, Betty C; Peterca, Mihai; Heiney, Paul A

    2007-09-12

    The design and synthesis of the first examples of AB4 and AB5 dendritic building blocks with complex architecture are reported. Structural and retrostructural analysis of supramolecular dendrimers self-assembled from hybrid dendrons based on different combinations of AB4 and AB5 building blocks with AB2 and AB3 benzyl ether dendrons demonstrated that none of these new hybrid dendrons exhibit the previously encountered conformations of libraries of benzyl ether dendrons. These hybrid dendrons enabled the discovery of some highly unusual tapered and conical dendrons generated by the intramolecular back-folding of their repeat units and of their apex. The new back-folded tapered dendrons have double thickness and self-assemble into pine-tree-like columns exhibiting a long-range 7/2 helical order. The back-folded conical dendrons self-assemble into spherical dendrimers. Non-back-folded truncated conical dendrons were also discovered. They self-assemble into spherical dendrimers with a less densely packed center. The discovery of dendrons displaying a novel crown-like conformation is also reported. Crown-like dendrons self-assemble into long-range 5/1 helical pyramidal columns. The long-range 7/2 and 5/1 helical structures were established by applying, for the first time, the helical diffraction theory to the analysis of X-ray patterns obtained from oriented fibers of supramolecular dendrimers. PMID:17705390

  5. Optimization and in vivo toxicity evaluation of G4.5 PAMAM dendrimer-risperidone complexes.

    Directory of Open Access Journals (Sweden)

    Maria Jimena Prieto

    Full Text Available Risperidone is an approved antipsychotic drug belonging to the chemical class of benzisoxazole. This drug has low solubility in aqueous medium and poor bioavailability due to extensive first-pass metabolism and high protein binding (>90%. Since new strategies to improve efficient treatments are needed, we studied the efficiency of anionic G4.5 PAMAM dendrimers as nanocarriers for this therapeutic drug. To this end, we explored dendrimer-risperidone complexation dependence on solvent concentration, pH and molar relationship. The best dendrimer-risperidone incorporation (46 risperidone molecules per dendrimer was achieved with a mixture of chloroform:methanol 50∶50 v/v solution pH 3. In addition, to explore the possible effects of this complex, in vivo studies were carried out in the zebrafish model. Changes in the development of dopaminergic neurons and motoneurons were studied using tyrosine hydroxylase and calretinin, respectively. Physiological changes were studied through histological sections stained with hematoxylin-eosin to observe possible morphological brain changes. The most significant changes were observed when larvae were treated with free risperidone, and no changes were observed when larvae were treated with the complex.

  6. Optimization and in vivo toxicity evaluation of G4.5 PAMAM dendrimer-risperidone complexes.

    Science.gov (United States)

    Prieto, Maria Jimena; del Rio Zabala, Nahuel Eduardo; Marotta, Cristian Hernán; Carreño Gutierrez, Hector; Arévalo Arévalo, Rosario; Chiaramoni, Nadia Silvia; del Valle Alonso, Silvia

    2014-01-01

    Risperidone is an approved antipsychotic drug belonging to the chemical class of benzisoxazole. This drug has low solubility in aqueous medium and poor bioavailability due to extensive first-pass metabolism and high protein binding (>90%). Since new strategies to improve efficient treatments are needed, we studied the efficiency of anionic G4.5 PAMAM dendrimers as nanocarriers for this therapeutic drug. To this end, we explored dendrimer-risperidone complexation dependence on solvent concentration, pH and molar relationship. The best dendrimer-risperidone incorporation (46 risperidone molecules per dendrimer) was achieved with a mixture of chloroform:methanol 50∶50 v/v solution pH 3. In addition, to explore the possible effects of this complex, in vivo studies were carried out in the zebrafish model. Changes in the development of dopaminergic neurons and motoneurons were studied using tyrosine hydroxylase and calretinin, respectively. Physiological changes were studied through histological sections stained with hematoxylin-eosin to observe possible morphological brain changes. The most significant changes were observed when larvae were treated with free risperidone, and no changes were observed when larvae were treated with the complex.

  7. UV-Photodimerization in Uracil-substituted dendrimers for high density data storage

    DEFF Research Database (Denmark)

    Lohse, Brian; Vestberg, Robert; Ivanov, Mario Tonev;

    2007-01-01

    Two series of uracil-functionalized dendritic macromolecules based on poly (amidoamine) PAMAM and 2,2-bis(hydroxymethylpropionic acid) bis-MPA backbones were prepared and their photoinduced (2 pi+2 pi) cycloaddition reactions upon exposure to UV light at 257 nm examined. Dendrimers up to 4th...

  8. Generation dependent singlet–singlet annihilation within multichromophoric dendrimers studied by polychromatic transient absorption

    NARCIS (Netherlands)

    Jordens, Sven; Belder, Gino De; Lor, Marc; Schweitzer, Gerd; Auweraer, Mark Van der; Weil, Tanja; Herrmann, Andreas; Wiesler, Uwe-M.; Müllen, Klaus; Schryver, Frans C. De

    2003-01-01

    Intramolecular kinetic processes in a series of shape-persistent meta- and para-substituted polyphenylene dendrimers bearing different peryleneimide chromophores at the rim have been investigated using time-resolved polychromatic transient absorption measurements. The influence of the generation num

  9. Dendrimer-curcumin conjugate: a water soluble and effective cytotoxic agent against breast cancer cell lines.

    Science.gov (United States)

    Debnath, Shawon; Saloum, Darin; Dolai, Sukanta; Sun, Chong; Averick, Saadyah; Raja, Krishnaswami; Fata, Jimmie E

    2013-12-01

    Curcumin, which is derived from the plant Curcuma longa, has received considerable attention as a possible anti-cancer agent. In cell culture, curcumin is capable of inducing apoptosis in cancer cells at concentrations that do not affect normal cells. One draw-back holding curcumin back from being an effective anti-cancer agent in humans is that it is almost completely insoluble in water and therefore has poor absorption and subsequently poor bioavailability. Here we have generated a number of curcumin derivatives (tetrahydro-curcumin, curcumin mono-carboxylic acid, curcumin mono-galactose, curcumin mono-alkyne and dendrimer-curcumin conjugate) to test whether any of them display both cytotoxicity and water solubility. Of those tested only dendrimer-curcumin conjugate exhibited both water solubility and cytotoxicity against SKBr3 and BT549 breast cancer cells. When compared to curcumin dissolved in DMSO, dendrimer-curcumin conjugate dissolved in water was significantly more effective in inducing cytotoxicity, as measured by the MTT assay and effectively induced cellular apoptosis measured by caspase-3 activation. Since dendrimer-curcumin conjugate is water soluble and capable of inducing potent cytotoxic effects on breast cancer cell lines, it may prove to be an effective anti-cancer therapy to be used in humans. PMID:23387971

  10. APPLICABILITY OF DENDRIMERS IN REAL LIFE PRACTICES: AN INTERFACE BETWEEN CHEMISTRY & BIOLOGY

    OpenAIRE

    Bina Rani; Raaz Maheshwari; Upma Singh; Magan Prasad; Chauhan, A K

    2012-01-01

    It is very tough to achieve 100 per cent branching in monodispersed samples and macromolecules. The profound branching makes the material unique for specialized applications. The objective of the article is to highlight the different dendritic morphologies in different kind of materials. Also, this article delineates the chemistry and numerous applications of dendrimers in day-to-day life.

  11. Preparation of metal-SAM-dendrimer-SAM-metal junctions by supramolecular metal transfer printing

    NARCIS (Netherlands)

    Nijhuis, Christian A.; ter Maat, Jurjen; Bisri, Satria Z.; Weusthof, Marcel H. H.; Salm, Cora; Schmitz, Jurriaan; Ravoo, Bart Jan; Huskensa, Jurriaan; Reinhoudt, David N.

    2008-01-01

    Metal-self-assembled monolayer (SAM)-dendrimer-SAM-metal junctions were prepared by a new type of metal transfer printing (mTP) that uses multiple beta-cyclodextrin (beta CD) host-guest interactions between a metal-coated stamp decorated with a monolayer of host molecules and a substrate which is fu

  12. Preparation of metal-SAM-dendrimer-SAM-metal junctions by supramolecular metal transfer printing

    NARCIS (Netherlands)

    Nijhuis, Christian A.; Maat, ter Jurjen; Bisri, Satria Z.; Weusthof, Marcel H.H.; Salm, Cora; Schmitz, Jurriaan; Ravoo, Bart Jan; Huskens, Jurriaan; Reinhoudt, David N.

    2008-01-01

    Metal-self-assembled monolayer (SAM)-dendrimer-SAM-metal junctions were prepared by a new type of metal transfer printing (mTP) that uses multiple ß-cyclodextrin (ßCD) host-guest interactions between a metal-coated stamp decorated with a monolayer of host molecules and a substrate which is functiona

  13. A simple new competition assay for heparin binding in serum applied to multivalent PAMAM dendrimers.

    Science.gov (United States)

    Bromfield, Stephen M; Posocco, Paola; Fermeglia, Maurizio; Pricl, Sabrina; Rodríguez-López, Julián; Smith, David K

    2013-05-25

    We report a competition assay using our recently reported dye Mallard Blue, which allows us to identify synthetic heparin binders in competitive media, including human serum - using this we gain insight into the ability of PAMAM dendrimers to bind heparin, with the interesting result that low-generation G2-PAMAM is the preferred heparin binder.

  14. 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.

  15. Investigation of drug loading behavior of dendrimers nano-vectors with synchrotron radiation hard X-ray fluorescence analysis

    International Nuclear Information System (INIS)

    Background: Synchrotron Radiation X-ray fluorescence analysis is an advanced method of quantitative elemental analysis. It is a scientific platform for life science, material science, and environmental science. Purpose: In this present study, the drug loading behavior of dendrimers nano-vectors was investigated by using the method of Synchrotron Radiation X-ray fluorescence analysis. Methods: The copper (Ⅱ) ions were loaded into acetyl-modified generation 5(G5) PAMAM dendrimers. We monitored and imaged the distribution of copper in A549 cell by Shanghai Synchrotron Radiation Facility (SSRF) to observe the cellular uptake of copper-dendrimers conjugates. Results: The results of hard X-ray fluorescence mapping showed a stronger fluorescence of Cu in the cells treated with G5-Ac-Cu than that of control. Conclusions: This investigation provided a method of using synchrotron radiation X-ray fluorescence analysis to study the drug loading behavior of dendrimers. (authors)

  16. Small Angle Neutron Scattering Study on Structure of PAMAM Dendrimer Encapsulation With Small Molecules in Aqueous Solution

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Dendrimers have very unique structural and physicochemical properties and many potential important applications, such as drug delivery, and therefore have been attracting research interests. It is interesting and important to investigate the interaction of

  17. Urea and thiourea modified polypropyleneimine dendrimers clear intracellular α-synuclein aggregates in a human cell line

    DEFF Research Database (Denmark)

    Laumann, Kristoffer; Boas, Ulrik; Larsen, Hjalte Martin;

    2015-01-01

    Synucleinopathies are neurodegenerative pathologies in which disease progression is closely correlated to brain accumulation of insoluble α-synuclein, a small protein abundantly expressed in neural tissue. Here, two types of modified polypropyleneimine (PPI) dendrimers having either urea or methy......Synucleinopathies are neurodegenerative pathologies in which disease progression is closely correlated to brain accumulation of insoluble α-synuclein, a small protein abundantly expressed in neural tissue. Here, two types of modified polypropyleneimine (PPI) dendrimers having either urea...

  18. Supramolecular coordination polymer formed from artificial light-harvesting dendrimer.

    Science.gov (United States)

    Lee, Hosoowi; Jeong, Young-Hwan; Kim, Joo-Ho; Kim, Inhye; Lee, Eunji; Jang, Woo-Dong

    2015-09-30

    We report the formation of supramolecular coordination polymers formed from multiporphyrin dendrimers (PZnPM; M = FB or Cu), composed of the focal freebase porphyrin (PFB) or cupper porphyrin (PCu) with eight zinc porphyrin (PZn) wings, and multipyridyl porphyrins (PyPM; M = FB or Cu), PFB or PCu with eight pyridyl groups, through multiple axial coordination interactions of pyridyl groups to PZns. UV-vis absorption spectra were recorded upon titration of PyPFB to PZnPFB. Differential spectra, obtained by subtracting the absorption of PZnPFB without guest addition as well as the absorption of PyPFB, exhibited clear isosbestic points with saturation binding at 1 equiv addition of PyPFB to PZnPFB. Job's plot analysis also indicated 1:1 stoichiometry for the saturation binding. The apparent association constant between PZnPFB and PyPFB (2.91 × 10(6) M(-1)), estimated by isothermal titration calorimetry, was high enough for fibrous assemblies to form at micromolar concentrations. The formation of a fibrous assembly from PZnPFB and PyPFB was visualized by atomic force microscopy and transmission electron microscopy (TEM). When a 1:1 mixture solution of PZnPFB and PyPFB (20 μM) in toluene was cast onto mica, fibrous assemblies with regular height (ca. 2 nm) were observed. TEM images obtained from 1:1 mixture solution of PZnPFB and PyPFB (0.1 wt %) in toluene clearly showed the formation of nanofibers with a regular diameter of ca. 6 nm. Fluorescence emission measurement of PZnPM indicated efficient intramolecular energy transfer from PZn to the focal PFB or PCu. By the formation of supramolecular coordination polymers, the intramolecular energy transfer changed to intermolecular energy transfer from PZnPM to PyPM. When the nonfluorescent PyPCu was titrated to fluorescent PZnPFB, fluorescence emission from the focal PFB was gradually decreased. By the titration of fluorescent PyPFB to nonfluorescent PZnPCu, fluorescence emission from PFB in PyPFB was gradually increased

  19. 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.

  20. Ion exchange behaviour of polymeric zirconium cations

    International Nuclear Information System (INIS)

    Polymeric zirconium cations formed in weakly acid solutions (pH2) are taken up strongly into macroporous cation exchange resins, while uptake into normal cation exchange resins (pore diameter about 1 nm) is low. Macroporous cation exchange resins loaded with polymeric Zr cations are shown to function as ligand exchange sorbents. (Authors)

  1. Divergent dendrimer synthesis via the Passerini three-component reaction and olefin cross-metathesis.

    Science.gov (United States)

    Kreye, Oliver; Kugele, Dennis; Faust, Lorenz; Meier, Michael A R

    2014-02-01

    The combination of the Passerini reaction and olefin cross-metathesis is shown to be a very useful approach for the divergent synthesis of dendrimers. Castor oil-derived platform chemicals, such as 10-undecenoic acid and 10-undecenal, are reacted in a Passerini reaction with an unsaturated isocyanide to obtain a core unit having three terminal double bonds. Subsequent olefin cross-metathesis with tert-butyl acrylate, followed by hydrogenation of the double bonds and hydrolysis of the tert-butyl ester, leads to an active core unit bearing three carboxylic acid groups as reactive sites. Iterative steps of the Passerini reaction with 10-undecenal and 10-isocyanodec-1-ene for branching, and olefin cross-metathesis with tert-butyl acrylate, followed by hydrogenation and hydrolysis allow the synthesis of a third-generation dendrimer. All steps of the synthesis are carefully characterized by NMR, GPC, MS, and IR.

  2. Dendrimer-Templated Ultrasmall and Multifunctional Photothermal Agents for Efficient Tumor Ablation.

    Science.gov (United States)

    Zhou, Zhengjie; Wang, Yitong; Yan, Yang; Zhang, Qiang; Cheng, Yiyun

    2016-04-26

    Ultrasmall and multifunctional nanoparticles are highly desirable for photothermal cancer therapy, but the synthesis of these nanoparticles remains a huge challenge. Here, we used a dendrimer as a template to synthesize ultrasmall photothermal agents and further modified them with multifunctional groups. Dendrimer-encapsulated nanoparticles (DENPs) including copper sulfide, platinum, and palladium nanoparticles possessed a sub-5 nm size and exhibited an excellent photothermal effect. DENPs were further modified with TAT or RGD peptides to facilitate their cellular uptake and targeting delivery to tumors. They were also decorated with fluorescent probes for real-time imaging and tracking of the particles' distribution. The in vivo study revealed RGD-modified DENPs efficiently reduced the tumor growth upon near-infrared irradiation. In all, our study provides a facile and flexible scaffold to prepare ultrasmall and multifunctional photothermal agents. PMID:27054555

  3. Metal dendrimers: synthesis of hierarchically stellated nanocrystals by sequential seed-directed overgrowth.

    Science.gov (United States)

    Weiner, Rebecca G; Skrabalak, Sara E

    2015-01-19

    Hierarchically organized structures are prevalent in nature, where such features account for the adhesion properties of gecko feet and the brilliant color variation of butterfly wings. Achieving artificial structures with multiscale features is of interest for metamaterials and biomimetic applications. However, the fabrication of such structures relies heavily on lithographic approaches, although self-assembly routes to superstructures are promising. Sequential seed-directed overgrowth is now demonstrated as a route to metal dendrimers, which are hierarchically branched nanocrystals (NCs) with a three-dimensional order analogous to that of molecular dendrimers. This method was applied to a model Au/Pd NC system; in general, the principle of sequential seed-directed overgrowth should enable the synthesis of new hierarchical inorganic structures with high symmetry.

  4. Low cytotoxicity fluorescent PAMAM dendrimer as gene carriers for monitoring the delivery of siRNA

    Energy Technology Data Exchange (ETDEWEB)

    Guan, Lingmei [Sichuan University, State Key Laboratory of Bio-resources and Eco-environment, The Ministry of Education, College of Life Sciences (China); Huang, Saipeng [Chinese Academy of Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Center for Molecular Sciences, Institute of Chemistry (China); Chen, Zhao [Xi’an Jiaotong University, School of Science (China); Li, Yanchao [Chinese Academy of Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Center for Molecular Sciences, Institute of Chemistry (China); Liu, Ke [Sichuan University, State Key Laboratory of Bio-resources and Eco-environment, The Ministry of Education, College of Life Sciences (China); Liu, Yang, E-mail: yliu@iccas.ac.cn; Du, Libo, E-mail: dulibo@iccas.ac.cn [Chinese Academy of Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Center for Molecular Sciences, Institute of Chemistry (China)

    2015-09-15

    Visual detection of gene vectors has attracted a great deal of attention due to the application of these vectors in monitoring and evaluating the effect of gene carriers in living cells. A non-viral vector, the fluorescent PAMAM dendrimer (F-PAMAM), was synthesized through conjugation of PAMAM dendrimers and fluorescein. In vitro and ex vivo experiments show that F-PAMAM exhibits superphotostability, low cytotoxicity and facilitates endocytosis by A549 cells. The vector has a high siRNA binding affinity and it increases the efficiency of cy5-siRNA delivery in A549 cells, in comparison with a cy5-siRNA monomer. Our results provide a new method for simultaneously monitoring the delivery of siRNA and its non-viral carriers in living cells.

  5. Nanosilver based anionic linear globular dendrimer with a special significant antiretroviral activity.

    Science.gov (United States)

    Ardestani, Mehdi Shafiee; Fordoei, Alireza Salehi; Abdoli, Asghar; Ahangari Cohan, Reza; Bahramali, Golnaz; Sadat, Seyed Mehdi; Siadat, Seyed Davar; Moloudian, Hamid; Nassiri Koopaei, Nasser; Bolhasani, Azam; Rahimi, Pooneh; Hekmat, Soheila; Davari, Mehdi; Aghasadeghi, Mohammad Reza

    2015-05-01

    HIV is commonly caused to a very complicated disease which has not any recognized vaccine, so designing and development of novel antiretroviral agents with specific application of nanomedicine is a globally interested research subject worldwide. In the current study, a novel structure of silver complexes with anionic linear globular dendrimer was synthesized, characterized and then assessed against HIV replication pathway in vitro as well. The results showed a very good yield of synthesis (up to 70%) for the nano-complex as well as a very potent significant (P < 0.05) antiretroviral activity with non-severe toxic effects in comparison with the Nevirapine as standard drug in positive control group. According to the present data, silver anionic linear globular dendrimers complex may have a promising future to inhibit replication of HIV viruse in clinical practice.

  6. Enhancement of cytotoxicity by combining pyrenyl-dendrimers and arene ruthenium metallacages.

    Science.gov (United States)

    Pitto-Barry, Anaïs; Zava, Olivier; Dyson, Paul J; Deschenaux, Robert; Therrien, Bruno

    2012-07-01

    Three generations of pyrenyl bis-MPA dendrimers with two different end-groups, acetonide (pyr(Gn)) or alcohol (pyr(Gn-OH)) (n = 1-3), were synthesized, and the pyrenyl group of the dendritic molecules was encapsulated in the arene ruthenium metallacages, [Ru(6)(p-cymene)(6)(OO∩OO)(3)(tpt)(2)](6+) (OO∩OO = 5,8-dioxydo-1,4-naphtaquinonato (donq) [1](6+) and 6,11-dioxydo-5,12-naphtacenedionato (dotq) [2](6+); tpt =2,4,6-tri(pyridin-4-yl)-1,3,5-triazine). The host-guest properties of [guest⊂1](6+) and [guest⊂2](6+) were studied in solution by NMR and UV-vis spectroscopic methods, thus allowing the determination of the affinity constants. Moreover, the cytotoxicity of these water-soluble host-guest systems and the pyrenyl-dendrimers was evaluated on human ovarian cancer cells. PMID:22716166

  7. Divergent dendrimer synthesis via the Passerini three-component reaction and olefin cross-metathesis.

    Science.gov (United States)

    Kreye, Oliver; Kugele, Dennis; Faust, Lorenz; Meier, Michael A R

    2014-02-01

    The combination of the Passerini reaction and olefin cross-metathesis is shown to be a very useful approach for the divergent synthesis of dendrimers. Castor oil-derived platform chemicals, such as 10-undecenoic acid and 10-undecenal, are reacted in a Passerini reaction with an unsaturated isocyanide to obtain a core unit having three terminal double bonds. Subsequent olefin cross-metathesis with tert-butyl acrylate, followed by hydrogenation of the double bonds and hydrolysis of the tert-butyl ester, leads to an active core unit bearing three carboxylic acid groups as reactive sites. Iterative steps of the Passerini reaction with 10-undecenal and 10-isocyanodec-1-ene for branching, and olefin cross-metathesis with tert-butyl acrylate, followed by hydrogenation and hydrolysis allow the synthesis of a third-generation dendrimer. All steps of the synthesis are carefully characterized by NMR, GPC, MS, and IR. PMID:24356926

  8. Vibrational spectra study of phosphorus dendrimer containing azobenzene, ammonium and carbamate groups

    Science.gov (United States)

    Furer, V. L.; Vandyukov, A. E.; Majoral, J. P.; Caminade, A. M.; Kovalenko, V. I.

    2013-06-01

    The FTIR and FT Raman spectra of the first generation dendrimers, possessing carbamate (G1) or ammonium (G2) terminal groups were studied. The structural optimization and normal mode analysis were performed for dendrimers on the basis of the density functional theory (DFT). These calculations of G2 gave the frequencies of vibrations, infrared intensities and Raman scattering activities for the E- and Z-forms of azobenzene unit. The energy difference between the E- and Z-forms of G2 is 27.36 kcal/mol. The calculated geometrical parameters and harmonic vibrational frequencies are predicted in a good agreement with the experimental data. It was found that dendrimers molecules have a concave lens structure with planar -O-C6H4-CHdbnd N-N(CH3)Pdbnd S, and -O-C6H4-Ndbnd N-C6H4-CHdbnd N-NH-Cdbnd O-CH2-N fragments and slightly non-planar cyclotriphosphazene core. The experimental IR and Raman spectra of dendrimers G1 and G2 were interpreted by means of potential energy distributions. Relying on DFT calculations a complete vibrational assignment is proposed. The strong band 1605 cm-1 in the IR spectra show marked changes of the optical density in dependence of substituents in the aromatic ring. The differences in the IR and Raman spectra of G2 for the E- and Z-forms of azobenzene units were cleared up. During structural isomerization of azobenzene units, redistribution of band intensities appears to a much higher extent than frequency shifts.

  9. Investigation of Dendrimer-based nanoparticles cellular uptake and cell tracking in a semiautomated microfluidic platform

    OpenAIRE

    Carvalho, Mariana Rodrigues; Maia, Fátima Raquel; Reis, R. L.; Oliveira, J. M.

    2016-01-01

    A microfluidic device such as Kima Pump and Vena8 biochip is able to realize functions that are not easily imaginable in conventional biological analysis, such as highly parallel, sophisticated high-throughput analysis and single-cell analysis in a well-defined manner [1]. Cancer cell tracking within the microfluidic model will be achieved by grafting fluorescent label probe Fluorescein-5(6)-isothiocyanate (FITC) to dendrimer nanoparticles allowing cell visualization by immunofluorescen...

  10. Generation dependent singlet–singlet annihilation within multichromophoric dendrimers studied by polychromatic transient absorption

    OpenAIRE

    Jordens, Sven; Belder, Gino De; Lor, Marc; Schweitzer, Gerd; Van der Auweraer, Mark; Weil, Tanja; Herrmann, Andreas; Wiesler, Uwe-M.; Müllen, Klaus; de Schryver, Frans C.

    2003-01-01

    Intramolecular kinetic processes in a series of shape-persistent meta- and para-substituted polyphenylene dendrimers bearing different peryleneimide chromophores at the rim have been investigated using time-resolved polychromatic transient absorption measurements. The influence of the generation number and different substitution patterns upon these processes was revealed by comparing different compounds. In particular, in multichromophoric systems a singlet–singlet annihilation process was de...

  11. Design of dendrimer-based drug delivery nanodevices with enhanced therapeutic efficacies

    Science.gov (United States)

    Kannan, Rangaramanujam

    2007-03-01

    Dendrimers and hyperbranched polymers possess highly branched architectures, with a large number of controllable, tailorable, `peripheral' functionalities. Since the surface chemistry of these materials can be modified with relative ease, these materials have tremendous potential in targeted drug delivery. They have significant potential compared to liposomes and nanoparticles, because of the reduced macrophage update, increased cellular transport, and the ability to modulate the local environment through functional groups. We are developing nanodevices based on dendritic systems for drug delivery, that contain a high drug payload, ligands, and imaging agents, resulting in `smart' drug delivery devices that can target, deliver, and signal. In collaboration with the Children's Hospital of Michigan, Karmanos Cancer Institute, and College of Pharmacy, we are testing the in vitro and in vivo response of these nanodevices, by adapting the chemistry for specific clinical applications such as asthma and cancer. These materials are characterized by UV/Vis spectroscopy, flow cytometry, fluorescence/confocal microscopy, and appropriate animal models. Our results suggest that: (1) We can prepare drug-dendrimer conjugates with drug payloads of greater than 50%, for a variety of drugs; (2) The dendritic polymers are capable of transporting and delivering drugs into cells faster than free drugs, with superior therapeutic efficiency. This can be modulated by the surface functionality of the dendrimer; (3) For chemotherapy drugs, the conjugates are a factor of 6-20 times more effective even in drug-resistant cell lines; (4) For corticosteroidal drugs, the dendritic polymers provide higher drug residence times in the lung, allowing for passive targeting. The ability of the drug-dendrimer-ligand conjugates to target specific asthma and cancer cells is currently being explored using in vitro and in vivo animal models.

  12. Dendrimer-Based Selective Proteostasis-Inhibition Strategy to Control NSCLC Growth and Progression.

    Science.gov (United States)

    Walworth, Kyla; Bodas, Manish; Campbell, Ryan John; Swanson, Doug; Sharma, Ajit; Vij, Neeraj

    2016-01-01

    Elevated valosin containing protein (VCP/p97) levels promote the progression of non-small cell lung carcinoma (NSCLC). Although many VCP inhibitors are available, most of these therapeutic compounds have low specificity for targeted tumor cell delivery. Hence, the primary aim of this study was to evaluate the in vitro efficacy of dendrimer-encapsulated potent VCP-inhibitor drug in controlling non-small cell lung carcinoma (NSCLC) progression. The VCP inhibitor(s) (either in their pure form or encapsulated in generation-4 PAMAM-dendrimer with hydroxyl surface) were tested for their in vitro efficacy in modulating H1299 (NSCLC cells) proliferation, migration, invasion, apoptosis and cell cycle progression. Our results show that VCP inhibition by DBeQ was significantly more potent than NMS-873 as evident by decreased cell proliferation (passay) and migration (passay), and increased apoptosis (passay) as compared to untreated control cells. Next, we found that dendrimer-encapsulated DBeQ (DDNDBeQ) treatment increased ubiquitinated-protein accumulation in soluble protein-fraction (immunoblotting) of H1299 cells as compared to DDN-control, implying the effectiveness of DBeQ in proteostasis-inhibition. We verified by immunostaining that DDNDBeQ treatment increases accumulation of ubiquitinated-proteins that co-localizes with an ER-marker, KDEL. We observed that proteostasis-inhibition with DDNDBeQ, significantly decreased cell migration rate (scratch-assay and transwell-invasion) as compared to the control-DDN treatment (passay) and increased caspase-3/7 mediated apoptotic cell death (pclonogenic-assay that DDNDBeQ treatment significantly (p<0.001) inhibits H1299 colony-formation as compared to control/DDN. Overall, encapsulation of potent VCP-inhibitor DBeQ into a dendrimer allows selective VCP-mediated proteostasis-inhibition for controlling NSCLC-tumor growth and progression to allow tumor-targeted sustained drug delivery. PMID:27434122

  13. Multiple antigen peptide dendrimer elicits antibodies for detecting rat and mouse growth hormone binding proteins

    OpenAIRE

    Aguilar, Roberto M.; Talamantes, Frank J.; Bustamante, Juan J.; Muñoz, Jesus; Treviño, Lisa R.; Martinez, Andrew O.; Haro, Luis S.

    2009-01-01

    The membrane-bound rat growth hormone receptor (GH-R) and an alternatively spliced isoform, the soluble rat GH binding protein (GH-BP), are comprised of identical N-terminal GH binding domains, however, their C-terminal sequences differ. Immunological reagents are needed to distinguish between the two isoforms in order to understand their respective roles in mediating the actions of GH. Accordingly, a tetravalent multiple antigen peptide (MAP) dendrimer with four identical branches of a C-ter...

  14. Vibrational spectra study of phosphorus dendrimer containing azobenzene units on the surface

    Science.gov (United States)

    Furer, V. L.; Vandyukov, A. E.; Majoral, J. P.; Caminade, A. M.; Kovalenko, V. I.

    2013-08-01

    The FTIR and FT Raman spectra of the first generation dendrimers, possessing oxybenzaldehyde (G1) or oxyphenylazobenzaldehyde (G2) terminal groups and sodium 4-[4-oxyphenyl)azo]-benzaldehyde (SOAB) were studied. The structural optimization and normal mode analysis were performed for dendrimer G2 on the basis of the density functional theory (DFT). These calculations gave the frequencies of vibrations, infrared intensities and Raman scattering activities for the E- and Z-forms of azobenzene unit. The energy differences between the E- and Z-forms are 12.62 and 25.16 kcal/mol for SOAB and G2. The calculated in gas phase dipole moments for the E- and Z-forms are equal to 20.86, 18.28 D (SOAB) and 7.56, 8.88 D (G2). The calculated geometrical parameters and harmonic vibrational frequencies are predicted in a good agreement with the experimental data. It was found that dendrimer G2 molecule has a concave lens structure with planar sbnd Osbnd C6H4sbnd CHdbnd Nsbnd N(CH3)Pdbnd S and sbnd Osbnd C6H4sbnd Ndbnd Nsbnd C6H4sbnd CHdbnd O fragments and slightly non-planar cyclotriphosphazene core. The experimental IR and Raman spectra of dendrimer G2 were interpreted by means of potential energy distributions. Relying on DFT calculations a complete vibrational assignment is proposed. The strong band 1598 cm-1 in the IR spectra show marked changes of the optical density in dependence of substituents in the aromatic ring. The differences in the IR and Raman spectra of SOAB and G2 for the E- and Z-forms of azobenzene units were cleared up. During structural isomerization of azobenzene units, redistribution of band intensities appears to a much higher extent than frequency shifts.

  15. Docosahexaenoic acid triglyceride-based microemulsions with an added dendrimer - Structural considerations.

    Science.gov (United States)

    Lidich, Nina; Francesca Ottaviani, M; Hoffman, Roy E; Aserin, Abraham; Garti, Nissim

    2016-12-01

    Omega fatty acids, mainly the triglyceride of docosahexaenoic acid (TG-DHA), are considered important nutraceuticals. These compounds are water-insoluble and their transport across membranes depends on their carriers. Dendrimers are known as drug carriers across cell membranes and also as permeation enhancers. The solubilization of TG-DHA and dendrimer into a microemulsion (ME) system serving as a carrier could be used for a targeted delivery in the future. The interactions between TG-DHA and second generation poly(propyleneimine) dendrimers (PPI-G2) and their effect on structural transitions of ME were explored along the water dilution line using electron paramagnetic resonance and pulsed-gradient spin-echo NMR along with other analytical techniques. The microviscosity, order parameter, and micropolarity of all studied systems decrease upon water dilution. Incorporation of TG-DHA reduces the microviscosity, order, and micropolarity, whereas PPI-G2 leads to an increase in these parameters. The effect of PPI-G2 is more pronounced at relative high contents (1 and 5wt%) where PPI-G2 interacts with the hydrophilic headgroups of the surfactants. In the macroscale, the effects of TG-DHA and PPI-G2 differ mostly in the bicontinuous region, where macroviscosity increases upon TG-DHA incorporation and decreases upon solubilization of 5wt% PPI-G2. From DSC measurements it was concluded that in the presence of TG-DHA the PPI-G2 is intercalated easily at the interface. PMID:27571688

  16. 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. PMID:26278524

  17. Dendrimer-magnetic nanoparticles as multiple stimuli responsive and enzymatic drug delivery vehicle

    Energy Technology Data Exchange (ETDEWEB)

    Chandra, Sudeshna; Noronha, Glen [Metallurgical and Materials Science Department, Indian Institute of Technology Bombay, Powai, Mumbai, 400076 (India); Dietrich, Sascha; Lang, Heinrich [Technische Universität Chemnitz, Institute of Chemistry, Straße der Nationen 62, d-09111 Chemnitz (Germany); Bahadur, Dhirendra, E-mail: dhirenb@iitb.ac.in [Metallurgical and Materials Science Department, Indian Institute of Technology Bombay, Powai, Mumbai, 400076 (India)

    2015-04-15

    Two different chain lengths of (poly)ethylene glycol-PAMAM dendrimers namely, L6-PEG-PAMAM and S6-PEG-PAMAM with six end-grafted ethylene glycol ether-tentacles of type CH{sub 2}CH{sub 2}C(O)O(CH{sub 2}CH{sub 2}O){sub 9}CH{sub 3} and CH{sub 2}CH{sub 2}C(O)O(CH{sub 2}CH{sub 2}O){sub 2}C{sub 2}H{sub 5}, respectively, were synthesized. These dendrimers have multiple σ-donor capabilities and therefore, were used for stabilizing the magnetite (Fe{sub 3}O{sub 4}) nanoparticles. Both the dendrimer-magnetic nanoparticles (L6-PEG-PAMAM-MNPs and S6-PEG-PAMAM-MNPs) were characterized by different spectroscopic and microstructural techniques. The nanoparticles were mesoporous and superparamagnetic and therefore, explored for their possible use in delivery of cancer drug, doxorubicin (DOX). In the developed drug delivery system, achieving high drug-loading efficiency with controllable release were the main challenges. The change in zeta potential and quenching of fluorescence intensity suggests chemical interaction between DOX and the nanoparticles. The loading efficiency was calculated to be over 95% with a sustained pH and temperature sensitive release. Further, enzyme cathepsin B has also been used to degrade the dendritic shell to trigger sustained drug release in the vicinity of tumor cells.

  18. 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.

  19. An amperometric chloramphenicol immunosensor based on cadmium sulfide nanoparticles modified-dendrimer bonded conducting polymer.

    Science.gov (United States)

    Kim, Dong-Min; Rahman, Md Aminur; Do, Minh Hien; Ban, Changill; Shim, Yoon-Bo

    2010-03-15

    An amperometric chloramphenicol (CAP) immunosensor was fabricated by covalently immobilizing anti-chloramphenicol acetyl transferase (anti-CAT) antibody on cadmium sulfide nanoparticles (CdS) modified-dendrimer that was bonded to the conducting polymer (poly 5, 2': 5', 2''-terthiophene-3'-carboxyl acid (poly-TTCA)) layer. The AuNPs, dendrimers, and CdS nanoparticles were deposited onto the polymer layer in order to enhance the sensitivity of the sensor probes. The particle sizes were determined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The immobilization of dendrimers, CdS, and anti-CAT were confirmed using energy disruptive spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), and quartz crystal microbalance (QCM) techniques. The detection of CAP was based on the competitive immuno-interaction between the free- and labeled-CAP for active sites of the anti-CAT. Hydrazine was used as the label for CAP, and it electrochemically catalyzed the reduction of H(2)O(2) at -0.35 V vs. Ag/AgCl. Under optimized conditions, the proposed immunosensor exhibited a linear range of CAP detection between 50 pg/mL and 950 pg/mL, and the detection limit was 45 pg/mL. The immunosensor was examined in real meat samples for the analysis of CAP.

  20. Piezoelectric sensor for sensitive determination of metal ions based on the phosphate-modified dendrimer

    Science.gov (United States)

    Wang, S. H.; Shen, C. Y.; Lin, Y. M.; Du, J. C.

    2016-08-01

    Heavy metal ions arising from human activities are retained strongly in water; therefore public water supplies must be monitored regularly to ensure the timely detection of potential problems. A phosphate-modified dendrimer film was investigated on a quartz crystal microbalance (QCM) for sensing metal ions in water at room temperature in this study. The chemical structures and sensing properties were characterized by Fourier transform infrared spectroscopy and QCM measurement, respectively. This phosphate-modified dendrimer sensor can directly detect metal ions in aqueous solutions. This novel sensor was evaluated for its capacity to sense various metal ions. The sensor exhibited a higher sensitivity level and shorter response time to copper(II) ions than other sensors. The linear detection range of the prepared QCM based on the phosphate-modified dendrimer was 0.0001 ∼ 1 μM Cu(II) ions (R2 = 0.98). The detection properties, including sensitivity, response time, selectivity, reusability, maximum adsorption capacity, and adsorption equilibrium constants, were also investigated.

  1. 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.

  2. Dynamical Interactions of 5-Fluorouracil Drug with Dendritic Peptide Vectors: The Impact of Dendrimer Generation, Charge, Counterions, and Structured Water.

    Science.gov (United States)

    De Luca, Sergio; Seal, Prasenjit; Ouyang, Defang; Parekh, Harendra S; Kannam, Sridhar Kumar; Smith, Sean C

    2016-06-30

    Molecular dynamics simulations are utilized to investigate the interactions between the skin cancer drug 5-fluorouracil (5FU) and peptide-based dendritic carrier systems. We find that these drug-carrier interactions do not conform to the traditional picture of long-time retention of the drug within a hydrophobic core of the dendrimer carrier. Rather, 5FU, which is moderately soluble in its own right, experiences weak, transient chattering interactions all over the dendrimer, mediated through multiple short-lived hydrogen bonding and close contact events. We find that charge on the periphery of the dendrimer actually has a negative effect on the frequency of drug-carrier interactions due to a counterion screening effect that has not previously been observed. However, charge is nevertheless an important feature since neutral dendrimers are shown to have a significant mutual attraction that can lead to clustering or agglomeration. This clustering is prevented due to charge repulsion for the titrated dendrimers, such that they remain independent in solution. PMID:27267604

  3. Tweaking Dendrimers and Dendritic Nanoparticles for Controlled Nano-bio Interactions: Potential Nanocarriers for Improved Cancer Targeting

    Science.gov (United States)

    Bugno, Jason; Hsu, Hao-Jui; Hong, Seungpyo

    2016-01-01

    Nanoparticles have shown great promise in the treatment of cancer, with a demonstrated potential in targeted drug delivery. Among a myriad of nanocarriers that have been recently developed, dendrimers have attracted a great deal of scientific interests due to their unique chemical and structural properties that allow for precise engineering of their characteristics. Despite this, the clinical translation of dendrimers has been hindered due to their drawbacks, such as scale-up issues, rapid systemic elimination, inefficient tumor accumulation, and limited drug loading. In order to overcome these limitations, a series of reengineered dendrimers have been recently introduced using various approaches, including: i) modifications of structure and surfaces; ii) integration with linear polymers; and iii) hybridization with other types of nanocarriers. Chemical modifications and surface engineering have tailored dendrimers to improve their pharmacokinetics and tissue permeation. Copolymerization of dendritic polymers with linear polymers has resulted in various amphiphilic copolymers with self-assembly capabilities and improved drug loading efficiencies. Hybridization with other nanocarriers integrates advantageous characteristics of both systems, which includes prolonged plasma circulation times and enhanced tumor targeting. This review provides a comprehensive summary of the newly emerging drug delivery systems that involve reengineering of dendrimers in an effort to precisely control their nano-bio interactions, mitigating their inherent weaknesses. PMID:26453160

  4. Anionic sulfonated and carboxylated PPI dendrimers with the EDA core: synthesis and characterization of selective metal complexing agents.

    Science.gov (United States)

    García-Gallego, Sandra; Cangiotti, Michela; Fiorani, Luigi; Fattori, Alberto; Muñoz-Fernández, Ma Ángeles; Gomez, Rafael; Ottaviani, M Francesca; de la Mata, F Javier

    2013-04-28

    Herein we describe the synthesis and characterization of new sulfonated and carboxylated poly(propyleneimino) (PPI) dendrimers with the ethylenediamino (EDA) core, at generations 1, 2 and 3. By means of UV-Vis and EPR spectroscopy, using Cu(2+) as a probe, we concluded that these dendrimers show a specific pattern in the coordination of metal ions. In agreement with the UV-Vis studies, EPR spectra of carboxylated compounds are constituted by 3 different signals which appear and then disappear with increasing copper concentration, corresponding to the saturation of different copper complexation sites. At the lowest copper concentration up to a 1:1 molar ratio between Cu(II) and the dendrimer, the spectrum is characteristic of a CuN2O2 coordination at the core of the dendrimer. The spectrum appearing at higher Cu(II) concentrations indicates a peripheral location of the ions coordinating one nitrogen and 3 oxygen atoms in a square planar geometry in restricted mobility conditions. For the highest concentrations tested, copper ions are confined at the external dendrimer surface with CuO4 coordination. For sulfonate systems, the EPR results are in line with a weaker interaction of Cu(II) with the nitrogen sites and a stronger interaction with the oxygen (SO3(-)) groups with respect to the interactions measured by EPR for carboxylate systems. PMID:23462972

  5. Preparation of poly(ethylene glycol)-modified poly(amido amine) dendrimers encapsulating gold nanoparticles and their heat-generating ability.

    Science.gov (United States)

    Haba, Yasuhiro; Kojima, Chie; Harada, Atsushi; Ura, Tomoaki; Horinaka, Hiromichi; Kono, Kenji

    2007-05-01

    Loading of HAuCl4 in poly(amido amine) G4 dendrimers having poly(ethylene glycol) (PEG) grafts at all chain ends and subsequent reduction with NaBH4 yielded PEG-modified dendrimers encapsulating gold nanoparticles (Au NPs) of ca. 2 nm diameter. The Au NPs held in the dendrimers were stable in aqueous solutions and dissolved readily, even after freeze-drying. Despite their small particle size, the heat-generating ability of Au NPs held in the dendrimer was comparable to that of widely used Au NPs with ca. 11 nm diameter under visible light irradiation. The observed excellent colloidal stability, high heat-generating ability and their biocompatible surface confirm that the PEG-modified dendrimers encapsulating Au NPs are a promising tool for photothermal therapy and imaging.

  6. p-Hydroxy benzoic acid-conjugated dendrimer nanotherapeutics as potential carriers for targeted drug delivery to brain: an in vitro and in vivo evaluation

    International Nuclear Information System (INIS)

    Dendrimers which are discrete nanostructures/nanoparticles are emerging as promising candidates for many nanomedicine applications. Ligand-conjugated dendrimer facilitate the delivery of therapeutics in a targeted manner. Small molecules such as p-hydroxyl benzoic acid (pHBA) were found to have high affinity for sigma receptors which are prominent in most parts of central nervous system and tumors. The aim of this study was to synthesize pHBA-dendrimer conjugates as colloidal carrier for site-specific delivery of practically water insoluble drug, docetaxel (DTX) to brain tumors and to determine its targeting efficiency. pHBA, a small molecule ligand was coupled to the surface amine groups of generation 4-PAMAM dendrimer via a carbodiimide reaction and loaded with DTX. The conjugation was confirmed by 1HNMR and FT-IR spectroscopy. In vitro release of drug from DTX-loaded pHBA-conjugated dendrimer was found to be less as compared to unconjugated dendrimers. The prepared drug delivery system exhibited good physico-chemical stability and decrease in hemolytic toxicity. Cell viability and cell uptake studies were performed against U87MG human glioblastoma cells and formulations exerted considerable anticancer effect than plain drug. Conjugation of dendrimer with pHBA significantly enhanced the brain uptake of DTX which was shown by the recovery of a higher percentage of the dose from the brain following administration of pHBA-conjugated dendrimers compared with unconjugated dendrimer or formulation in clinical use (Taxotere®). Therefore, pHBA conjugated dendrimers could be an efficient delivery vehicle for the targeting of anticancer drugs to brain tumors

  7. p-Hydroxy benzoic acid-conjugated dendrimer nanotherapeutics as potential carriers for targeted drug delivery to brain: an in vitro and in vivo evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Swami, Rajan; Singh, Indu [National Institute of Pharmaceutical Education & Research (NIPER), Department of Pharmaceutics (India); Kulhari, Hitesh [CSIR-Indian Institute of Chemical Technology, Medicinal Chemistry & Pharmacology Division (India); Jeengar, Manish Kumar [National Institute of Pharmaceutical Education & Research (NIPER), Departmentof Pharmacology (India); Khan, Wahid, E-mail: wahid@niperhyd.ac.in; Sistla, Ramakrishna, E-mail: sistla@iict.res.in, E-mail: rksistla@yahoo.com [National Institute of Pharmaceutical Education & Research (NIPER), Department of Pharmaceutics (India)

    2015-06-15

    Dendrimers which are discrete nanostructures/nanoparticles are emerging as promising candidates for many nanomedicine applications. Ligand-conjugated dendrimer facilitate the delivery of therapeutics in a targeted manner. Small molecules such as p-hydroxyl benzoic acid (pHBA) were found to have high affinity for sigma receptors which are prominent in most parts of central nervous system and tumors. The aim of this study was to synthesize pHBA-dendrimer conjugates as colloidal carrier for site-specific delivery of practically water insoluble drug, docetaxel (DTX) to brain tumors and to determine its targeting efficiency. pHBA, a small molecule ligand was coupled to the surface amine groups of generation 4-PAMAM dendrimer via a carbodiimide reaction and loaded with DTX. The conjugation was confirmed by {sup 1}HNMR and FT-IR spectroscopy. In vitro release of drug from DTX-loaded pHBA-conjugated dendrimer was found to be less as compared to unconjugated dendrimers. The prepared drug delivery system exhibited good physico-chemical stability and decrease in hemolytic toxicity. Cell viability and cell uptake studies were performed against U87MG human glioblastoma cells and formulations exerted considerable anticancer effect than plain drug. Conjugation of dendrimer with pHBA significantly enhanced the brain uptake of DTX which was shown by the recovery of a higher percentage of the dose from the brain following administration of pHBA-conjugated dendrimers compared with unconjugated dendrimer or formulation in clinical use (Taxotere{sup ®}). Therefore, pHBA conjugated dendrimers could be an efficient delivery vehicle for the targeting of anticancer drugs to brain tumors.

  8. Liquid-solid extraction of cationic metals by cationic amphiphiles

    International Nuclear Information System (INIS)

    In the field of selective separation for recycling of spent nuclear fuel, liquid-liquid extraction processes are widely used (PUREX, DIAMEX..) in industrial scale. In order to guarantee a sustainable nuclear energy for the forthcoming generations, alternative reprocessing techniques are under development. One of them bases on the studies from Heckmann et al in the 80's and consists in selectively precipitating actinides from aqueous waste solutions by cationic surfactants (liquid-solid extraction). This technique has some interesting advantages over liquid-liquid extraction techniques, because several steps are omitted like stripping or solvent washing. Moreover, the amount of waste is decreased considerably, since no contaminated organic solvent is produced. In this thesis, we have carried out a physico-chemical study to understand the specific interactions between the metallic cations with the cationic surfactant. First, we have analysed the specific effect of the different counter-ions (Cl-, NO3-, C2O42-) and then the effect of alkaline cations on the structural properties of the surfactant aggregation in varying thermodynamical conditions. Finally, different multivalent cations (Cu2+, Zn2+, UO22+, Fe3+, Nd3+, Eu3+, Th4+) were considered; we have concluded that depending on the anionic complex of these metals formed in acidic media, we can observe either an adsorption at the micellar interface or not. This adsorption has a large influence of the surfactant aggregation properties and determines the limits of the application in term of ionic strength, temperature and surfactant concentration. (author)

  9. The SPL7013 dendrimer destabilizes the HIV-1 gp120-CD4 complex

    Science.gov (United States)

    Nandy, Bidisha; Saurabh, Suman; Sahoo, Anil Kumar; Dixit, Narendra M.; Maiti, Prabal K.

    2015-11-01

    The poly (l-lysine)-based SPL7013 dendrimer with naphthalene disulphonate surface groups blocks the entry of HIV-1 into target cells and is in clinical trials for development as a topical microbicide. Its mechanism of action against R5 HIV-1, the HIV-1 variant implicated in transmission across individuals, remains poorly understood. Using docking and fully atomistic MD simulations, we find that SPL7013 binds tightly to R5 gp120 in the gp120-CD4 complex but weakly to gp120 alone. Further, the binding, although to multiple regions of gp120, does not occlude the CD4 binding site on gp120, suggesting that SPL7013 does not prevent the binding of R5 gp120 to CD4. Using MD simulations to compute binding energies of several docked structures, we find that SPL7013 binding to gp120 significantly weakens the gp120-CD4 complex. Finally, we use steered molecular dynamics (SMD) to study the kinetics of the dissociation of the gp120-CD4 complex in the absence of the dendrimer and with the dendrimer bound in each of the several stable configurations to gp120. We find that SPL7013 significantly lowers the force required to rupture the gp120-CD4 complex and accelerates its dissociation. Taken together, our findings suggest that SPL7013 compromises the stability of the R5 gp120-CD4 complex, potentially preventing the accrual of the requisite number of gp120-CD4 complexes across the virus-cell interface, thereby blocking virus entry.The poly (l-lysine)-based SPL7013 dendrimer with naphthalene disulphonate surface groups blocks the entry of HIV-1 into target cells and is in clinical trials for development as a topical microbicide. Its mechanism of action against R5 HIV-1, the HIV-1 variant implicated in transmission across individuals, remains poorly understood. Using docking and fully atomistic MD simulations, we find that SPL7013 binds tightly to R5 gp120 in the gp120-CD4 complex but weakly to gp120 alone. Further, the binding, although to multiple regions of gp120, does not occlude

  10. Cationic speciation in nonaqueous media

    International Nuclear Information System (INIS)

    Electronic spectra of solutions of d transition elements in the superacids HF, H2SO4, HSO3F, and CF3SO3H and in chloroaluminate melts indicate that in acidic monaqueous media the elements are present as solvated cations, whereas in basic media the speciation is anionic, the same situation as in aqueous solutions. Further, in very highly acidic media, cations in very low oxidation states are stable (e.g., Ti2+), but these disproportionate on addition of base to the system. In this paper spectra, where available, of U, Np, and Pu in oxidation states III and IV in aqueous media, in protonic superacids, and in chloroaluminates are presented to postulate cationic speciation of these early actinides in highly acidic media

  11. Constitutional Isomers of Dendrimer-like Star Polymers: Design, Synthesis and Conformational and Structural Properties; TOPICAL

    International Nuclear Information System (INIS)

    The design, synthesis and solution properties of six constitutional isomers of dendrimer-like star polymers is described. Each of the polymers have comparable molecular weights ((approx) 80,000 g/mol), narrow polydispersities ( and lt; 1.19) and an identical number of branching junctures (45) and surface hydroxyl functionalities (48). The only difference in the six isomers is the placement of the branching junctures. The polymers are constructed from high molecular weight poly(e-caprolactone) with branching junctures derived from 2,2'-bis(hydroxylmethyl) propionic acid (bis-MPA) emanating from a central core. The use of various generations of dendritic initiators and dendrons coupled with the ring opening polymerization of e-caprolactones allowed a modular approach to the dendrimer-like star polymer isomers. The most pronounced effects on the physical properties/morphology and hydrodynamic volume was for those polymers in which the branching was distributed throughout the sample in a dendrimer-like fashion. The versatility of this approach has provided the possibility of understanding the relationship between architecture and physical properties. Dynamic light scattering and small angle X-ray scattering techniques were used to determine the hydrodynamic radius Rh and radius of gyration Rg respectively. The relationship between Rg and molecular weight was indicative of a compact star-like structure, and did not show advanced bias towards either the dense core or dense shell models. The radial density distribution of the isomers was therefore modeled according to a many arm star polymer, and good agreement was found with experimental measures of Rh/Rg

  12. Electrogenerated chemiluminescence reactions between the [Ru(bpy)3](2+) complex and PAMAM GX.0 dendrimers in an aqueous medium.

    Science.gov (United States)

    Jimenez-Ruiz, A; Grueso, E; Perez-Tejeda, P

    2015-10-01

    Electrogenerated chemiluminescence, ECL, reactions between tris(2,2'-bipyridine)ruthenium(II), [Ru(bpy)3](2+), and PAMAM GX.0 (X=1 and 2) dendrimers in an aqueous medium were carried out at pH10 (fully deprotonated dendrimer surface). ECL was detected in the presence of GX.0 dendrimers without addition of any known coreactant. Atomic force microscopy, AFM, measurements for GX.0 dendrimers in the presence of the [Ru(bpy)3](2+) complex were also done. AFM images showed the existence of aggregates (pillars) of globular shape, as well as interdendrimer networks forming fibers in the x-y direction for dendrimer aqueous solutions. ECL and AFM results in cooperation suggest that the coreactant effect of the end amine groups is improved by both the dendritic branched shells and the globular z-type aggregates. The ECL efficiency trends as a function of [GX.0] (whole range) can be interpreted taking into account the coreactant effect modulated by the presence of the z and x-y type aggregates. Importantly, ECL efficiency values can be taken as a measure of the change induced on the dendrimer aggregation in aqueous solutions when their concentrations rise. Redox potentials of the [Ru(bpy)3](3+/2+) couple in the presence of the G1.0 and G2.0 dendrimers were also determined. PMID:26190671

  13. Enzyme-responsive doxorubicin release from dendrimer nanoparticles for anticancer drug delivery

    Directory of Open Access Journals (Sweden)

    Lee SJ

    2015-08-01

    Full Text Available Sang Joon Lee,1,* Young-Il Jeong,2,* Hyung-Kyu Park,3 Dae Hwan Kang,2,4 Jong-Suk Oh,3 Sam-Gyu Lee,5 Hyun Chul Lee31Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, 2Biomedical Research Institute, Pusan National University Hospital, Busan, 3Department of Microbiology, Chonnam National University Medical School, Gwangju, 4Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Gyeongnam, 5Department of Physical and Rehabilitation Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea*These authors contributed equally to this workBackground: Since cancer cells are normally over-expressed cathepsin B, we synthesized dendrimer-methoxy poly(ethylene glycol (MPEG-doxorubicin (DOX conjugates using a cathepsin B-cleavable peptide for anticancer drug targeting.Methods: Gly-Phe-Leu-Gly peptide was conjugated with the carboxylic acid end groups of a dendrimer, which was then conjugated with MPEG amine and doxorubicin by aid of carbodiimide chemistry (abbreviated as DendGDP. Dendrimer-MPEG-DOX conjugates without Gly-Phe-Leu-Gly peptide linkage was also synthesized for comparison (DendDP. Nanoparticles were then prepared using a dialysis procedure.Results: The synthesized DendGDP was confirmed with 1H nuclear magnetic resonance spectroscopy. The DendDP and DendGDP nanoparticles had a small particle size of less than 200 nm and had a spherical morphology. DendGDP had cathepsin B-sensitive drug release properties while DendDP did not show cathepsin B sensitivity. Further, DendGDP had improved anticancer activity when compared with doxorubicin or DendDP in an in vivo CT26 tumor xenograft model, ie, the volume of the CT26 tumor xenograft was significantly inhibited when compared with xenografts treated with doxorubicin or DendDP nanoparticles. The DendGDP nanoparticles were found to be relatively concentrated in the tumor tissue and

  14. Dendrimer-Based Selective Proteostasis-Inhibition Strategy to Control NSCLC Growth and Progression

    Science.gov (United States)

    Walworth, Kyla; Bodas, Manish; Campbell, Ryan John; Swanson, Doug; Sharma, Ajit; Vij, Neeraj

    2016-01-01

    Elevated valosin containing protein (VCP/p97) levels promote the progression of non-small cell lung carcinoma (NSCLC). Although many VCP inhibitors are available, most of these therapeutic compounds have low specificity for targeted tumor cell delivery. Hence, the primary aim of this study was to evaluate the in vitro efficacy of dendrimer-encapsulated potent VCP-inhibitor drug in controlling non-small cell lung carcinoma (NSCLC) progression. The VCP inhibitor(s) (either in their pure form or encapsulated in generation-4 PAMAM-dendrimer with hydroxyl surface) were tested for their in vitro efficacy in modulating H1299 (NSCLC cells) proliferation, migration, invasion, apoptosis and cell cycle progression. Our results show that VCP inhibition by DBeQ was significantly more potent than NMS-873 as evident by decreased cell proliferation (p<0.0001, MTT-assay) and migration (p<0.05; scratch-assay), and increased apoptosis (p<0.05; caspase-3/7-assay) as compared to untreated control cells. Next, we found that dendrimer-encapsulated DBeQ (DDNDBeQ) treatment increased ubiquitinated-protein accumulation in soluble protein-fraction (immunoblotting) of H1299 cells as compared to DDN-control, implying the effectiveness of DBeQ in proteostasis-inhibition. We verified by immunostaining that DDNDBeQ treatment increases accumulation of ubiquitinated-proteins that co-localizes with an ER-marker, KDEL. We observed that proteostasis-inhibition with DDNDBeQ, significantly decreased cell migration rate (scratch-assay and transwell-invasion) as compared to the control-DDN treatment (p<0.05). Moreover, DDNDBeQ treatment showed a significant decrease in cell proliferation (p<0.01, MTT-assay) and increased caspase-3/7 mediated apoptotic cell death (p<0.05) as compared to DDN-control. This was further verified by cell cycle analysis (propidium-iodide-staining) that demonstrated significant cell cycle arrest in the G2/M-phase (p<0.001) by DDNDBeQ treatment as compared to control-DDN. Moreover

  15. Dendrimer-Based Selective Proteostasis-Inhibition Strategy to Control NSCLC Growth and Progression.

    Directory of Open Access Journals (Sweden)

    Kyla Walworth

    Full Text Available Elevated valosin containing protein (VCP/p97 levels promote the progression of non-small cell lung carcinoma (NSCLC. Although many VCP inhibitors are available, most of these therapeutic compounds have low specificity for targeted tumor cell delivery. Hence, the primary aim of this study was to evaluate the in vitro efficacy of dendrimer-encapsulated potent VCP-inhibitor drug in controlling non-small cell lung carcinoma (NSCLC progression. The VCP inhibitor(s (either in their pure form or encapsulated in generation-4 PAMAM-dendrimer with hydroxyl surface were tested for their in vitro efficacy in modulating H1299 (NSCLC cells proliferation, migration, invasion, apoptosis and cell cycle progression. Our results show that VCP inhibition by DBeQ was significantly more potent than NMS-873 as evident by decreased cell proliferation (p<0.0001, MTT-assay and migration (p<0.05; scratch-assay, and increased apoptosis (p<0.05; caspase-3/7-assay as compared to untreated control cells. Next, we found that dendrimer-encapsulated DBeQ (DDNDBeQ treatment increased ubiquitinated-protein accumulation in soluble protein-fraction (immunoblotting of H1299 cells as compared to DDN-control, implying the effectiveness of DBeQ in proteostasis-inhibition. We verified by immunostaining that DDNDBeQ treatment increases accumulation of ubiquitinated-proteins that co-localizes with an ER-marker, KDEL. We observed that proteostasis-inhibition with DDNDBeQ, significantly decreased cell migration rate (scratch-assay and transwell-invasion as compared to the control-DDN treatment (p<0.05. Moreover, DDNDBeQ treatment showed a significant decrease in cell proliferation (p<0.01, MTT-assay and increased caspase-3/7 mediated apoptotic cell death (p<0.05 as compared to DDN-control. This was further verified by cell cycle analysis (propidium-iodide-staining that demonstrated significant cell cycle arrest in the G2/M-phase (p<0.001 by DDNDBeQ treatment as compared to control

  16. Investigation on Aqueous Solution Properties of Dendrimer PPI%树状高分子PPI水溶液性质的研究

    Institute of Scientific and Technical Information of China (English)

    徐敏; 严晓虎; 余学海

    2001-01-01

    Aqueous solution properties of dendrimer PPI[Poly(propylene imine)] were studied by measuring viscosity parameters. Particularly on the extremely dilute concentration region were focused on. The adsorption constant k, critical concentration ca, intrinsic viscosity[η], intermolecular association constant Km and hydrodynamic contact concentration cs were calculated. And the generation number dependence of these parameters were also studied. From the results, the unique behavior of dendrimer solution was explained preliminary. The adsorption phenomenon of polymer solution is general, and the adsorption theory is also fit for dendrimers. Furthermore, the dynamic contact concentration cs was determined by a simple viscosity method for the first time.

  17. Synthesis of Non-Cytotoxic Poly(Ester-Amine Dendrimers as Potential Solubility Enhancers for Drugs: Methotrexate as a Case Study

    Directory of Open Access Journals (Sweden)

    Patricia Guadarrama

    2010-11-01

    Full Text Available This study describes the synthesis of two new families of dendrimers based on the esterification of N-alkylated 3-amine-1-propanol with two different cores, adipic acid (1st and 2nd generations and ethylenediamine (generation 1.5, both with carboxylic acid end groups, offering a wide variety of further modifications at the periphery. According to the cytotoxic evaluation of the dendrimers and their possible degradation products within cell lines, these materials could be considered as innocuous. In preliminary studies, the synthesized dendrimers proved to be potential enhancers of solubility of highly hydrophobic drugs, like methotrexate, widely used in chemotherapy.

  18. Research progress in cation-π interactions

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Cation-π interaction is a potent intermolecular interaction between a cation and an aromatic system,which has been viewed as a new kind of binding force,as being compared with the classical interactions(e.g. hydrogen bonding,electrostatic and hydrophobic interactions). Cation-π interactions have been observed in a wide range of biological contexts. In this paper,we present an overview of the typical cation-π interactions in biological systems,the experimental and theoretical investigations on cation-π interactions,as well as the research results on cation-π interactions in our group.

  19. Research progress in cation-π interactions

    Institute of Scientific and Technical Information of China (English)

    CHENG JiaGao; LUO XiaoMin; YAN XiuHua; LI Zhong; TANG Yun; JIANG HuaLiang; ZHU WeiLiang

    2008-01-01

    Cation-π interaction is a potent intermolecular interaction between a cation and an aromatic system, which has been viewed as a new kind of binding force, as being compared with the classical interac-tions (e.g. hydrogen bonding, electrostatic and hydrophobic interactions). Cation-π interactions have been observed in a wide range of biological contexts. In this paper, we present an overview of the typi-cal cation-π interactions in biological systems, the experimental and theoretical investigations on cation-π interactions, as well as the research results on cation-π interactions in our group.

  20. Translational and rotational diffusion of flexible PEG and rigid dendrimer probes in sodium caseinate dispersions and acid gels

    NARCIS (Netherlands)

    Salami, S.; Rondeau-Mouro, C.; Barhoum, M.; Duynhoven, van J.P.M.; Mariette, F.

    2014-01-01

    The dynamics of rigid dendrimer and flexible PEG probes in sodium caseinate dispersions and acid gels, including both translational diffusion and rotational diffusion, were studied by NMR. Above the onset of the close-packing limit (C ~ 10 g/100 g H2O), translational diffusion of the probe depended

  1. Enhanced activity of carbosilane dendrimers against HIV when combined with reverse transcriptase inhibitor drugs: searching for more potent microbicides

    Science.gov (United States)

    Vacas-Córdoba, Enrique; Galán, Marta; de la Mata, Francisco J; Gómez, Rafael; Pion, Marjorie; Muñoz-Fernández, M Ángeles

    2014-01-01

    Self-administered topical microbicides or oral preexposure prophylaxis could be very helpful tools for all risk groups to decrease the human immunodeficiency virus (HIV)-1 infection rates. Up until now, antiretrovirals (ARVs) have been the most advanced microbicide candidates. Nevertheless, the majority of clinical trials has failed in HIV-1 patients. Nanotechnology offers suitable approaches to develop novel antiviral agents. Thereby, new nanosystems, such as carbosilane dendrimers, have been shown to be safe and effective compounds against HIV with great potential as topical microbicides. In addition, because most of the attempts to develop effective topical microbicides were unsuccessful, combinatorial strategies could be a valid approach when designing new microbicides. We evaluated various combinations of anionic carbosilane dendrimers with sulfated (G3-S16) and naphthyl sulfonated (G2-NF16) ended groups with different ARVs against HIV-1 infection. The G3-S16 and G2-NF16 dendrimers showed a synergistic or additive activity profile with zidovudine, efavirenz, and tenofovir in the majority of the combinations tested against the X4 and R5 tropic HIV-1 in cell lines, as well as in human primary cells. Therefore, the combination of ARVs and polyanionic carbosilane dendrimers enhances the antiviral potency of the individual compounds, and our findings support further clinical research on combinational approaches as potential microbicides to block the sexual transmission of HIV-1. PMID:25114528

  2. Synthesis and In Vitro Cancer Cell Targeting of Folate-Functionalized Biodegradable Amphiphilic Dendrimer-Like Star Polymers

    NARCIS (Netherlands)

    Cao, Weiqiang; Zhou, Jing; Wang, Yong; Zhu, Lei

    2010-01-01

    By coupling a well-defined PLLA star polymer with six carboxylic acid-terminated polyester dendrons based on 2,2-bis(hydroxymethyl)propionic acid, a biodegradable dendrimer-like star polymer (DLSP) with multiple carboxylic acid groups at the outer surface was successfully synthesized. Conjugation of

  3. Self-assembled films of dendrimers and metallophthalocyanines as FET-based glucose biosensors.

    Science.gov (United States)

    Vieira, Nirton C S; Figueiredo, Alessandra; de Queiroz, Alvaro A A; Zucolotto, Valtencir; Guimarães, Francisco E G

    2011-01-01

    Separative extended gate field effect transistor (SEGFET) type devices have been used as an ion sensor or biosensor as an alternative to traditional ion sensitive field effect transistors (ISFETs) due to their robustness, ease of fabrication, low cost and possibility of FET isolation from the chemical environment. The layer-by-layer technique allows the combination of different materials with suitable properties for enzyme immobilization on simple platforms such as the extended gate of SEGFET devices enabling the fabrication of biosensors. Here, glucose biosensors based on dendrimers and metallophthalocyanines (MPcs) in the form of layer-by-layer (LbL) films, assembled on indium tin oxide (ITO) as separative extended gate material, has been produced. NH(3)(+) groups in the dendrimer allow electrostatic interactions or covalent bonds with the enzyme (glucose oxidase). Relevant parameters such as optimum pH, buffer concentration and presence of serum bovine albumin (BSA) in the immobilization process were analyzed. The relationship between the output voltage and glucose concentration shows that upon detection of a specific analyte, the sub-products of the enzymatic reaction change the pH locally, affecting the output signal of the FET transducer. In addition, dendritic layers offer a nanoporous environment, which may be permeable to H(+) ions, improving the sensibility as modified electrodes for glucose biosensing. PMID:22163704

  4. Self-Assembled Films of Dendrimers and Metallophthalocyanines as FET-Based Glucose Biosensors

    Directory of Open Access Journals (Sweden)

    Alessandra Figueiredo

    2011-10-01

    Full Text Available Separative extended gate field effect transistor (SEGFET type devices have been used as an ion sensor or biosensor as an alternative to traditional ion sensitive field effect transistors (ISFETs due to their robustness, ease of fabrication, low cost and possibility of FET isolation from the chemical environment. The layer-by-layer technique allows the combination of different materials with suitable properties for enzyme immobilization on simple platforms such as the extended gate of SEGFET devices enabling the fabrication of biosensors. Here, glucose biosensors based on dendrimers and metallophthalocyanines (MPcs in the form of layer-by-layer (LbL films, assembled on indium tin oxide (ITO as separative extended gate material, has been produced. NH3+ groups in the dendrimer allow electrostatic interactions or covalent bonds with the enzyme (glucose oxidase. Relevant parameters such as optimum pH, buffer concentration and presence of serum bovine albumin (BSA in the immobilization process were analyzed. The relationship between the output voltage and glucose concentration shows that upon detection of a specific analyte, the sub-products of the enzymatic reaction change the pH locally, affecting the output signal of the FET transducer. In addition, dendritic layers offer a nanoporous environment, which may be permeable to H+ ions, improving the sensibility as modified electrodes for glucose biosensing.

  5. 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.

  6. An Alkane-Soluble Dendrimer as Electron-Transport Layer in Polymer Light-Emitting Diodes.

    Science.gov (United States)

    Zhong, Zhiming; Zhao, Sen; Pei, Jian; Wang, Jian; Ying, Lei; Peng, Junbiao; Cao, Yong

    2016-08-10

    Polymer light-emitting diodes (PLEDs) have attracted broad interest due to their solution-processable properties. It is well-known that to achieve better performance, organic light-emitting diodes require multilayer device structures. However, it is difficult to realize multilayer device structures by solution processing for PLEDs. Because most semiconducting polymers have similar solubility in common organic solvents, such as toluene, xylene, chloroform, and chlorobenzene, the deposition of multilayers can cause layers to mix together and damage each layer. Herein, a novel semiorthogonal solubility relationship was developed and demonstrated. For the first time, an alkane-soluble dendrimer is utilized as the electron-transport layer (ETL) in PLEDs via a solution-based process. With the dendrimer ETL, the external quantum efficiency increases more than threefold. This improvement in the device performance is attributed to better exciton confinement, improved exciton energy transfer, and better charge carrier balance. The semiorthogonal solubility provided by alkane offers another process dimension in PLEDs. By combining them with water/alcohol-soluble polyelectrolytes, more exquisite multilayer devices can be fabricated to achieve high device performance, and new device structures can be designed and realized.

  7. Efficacy of HIV antiviral polyanionic carbosilane dendrimer G2-S16 in the presence of semen

    Science.gov (United States)

    Ceña-Diez, Rafael; García-Broncano, Pilar; de la Mata, Francisco Javier; Gómez, Rafael; Muñoz-Fernández, Mª Ángeles

    2016-01-01

    The development of a safe and effective microbicide to prevent the sexual transmission of human immunodeficiency virus (HIV)-1 is urgently needed. Unfortunately, the majority of microbicides, such as poly(L-lysine)-dendrimers, anionic polymers, or antiretrovirals, have proved inactive or even increased the risk of HIV infection in clinical trials, most probably due to the fact that these compounds failed to prevent semen-exposed HIV infection. We showed that G2-S16 dendrimer exerts anti-HIV-1 activity at an early stage of viral replication, blocking the gp120/CD4/CCR5 interaction and providing a barrier to infection for long periods, confirming its multifactorial and nonspecific ability. Previously, we demonstrated that topical administration of G2-S16 prevents HIV transmission in humanized BLT mice without irritation or vaginal lesions. Here, we demonstrated that G2-S16 is active against mock- and semen-exposed HIV-1 and could be a promising microbicide against HIV infection. PMID:27313457

  8. Thermodynamic stability and structural properties of cluster crystals formed by amphiphilic dendrimers

    Science.gov (United States)

    Lenz, Dominic A.; Mladek, Bianca M.; Likos, Christos N.; Blaak, Ronald

    2016-05-01

    We pursue the goal of finding real-world examples of macromolecular aggregates that form cluster crystals, which have been predicted on the basis of coarse-grained, ultrasoft pair potentials belonging to a particular mathematical class [B. M. Mladek et al., Phys. Rev. Lett. 46, 045701 (2006)]. For this purpose, we examine in detail the phase behavior and structural properties of model amphiphilic dendrimers of the second generation by means of monomer-resolved computer simulations. On augmenting the density of these systems, a fluid comprised of clusters that contain several overlapping and penetrating macromolecules is spontaneously formed. Upon further compression of the system, a transition to multi-occupancy crystals takes place, the thermodynamic stability of which is demonstrated by means of free-energy calculations, and where the FCC is preferred over the BCC-phase. Contrary to predictions for coarse-grained theoretical models in which the particles interact exclusively by effective pair potentials, the internal degrees of freedom of these molecules cause the lattice constant to be density-dependent. Furthermore, the mechanical stability of monodisperse BCC and FCC cluster crystals is restricted to a bounded region in the plane of cluster occupation number versus density. The structural properties of the dendrimers in the dense crystals, including their overall sizes and the distribution of monomers are also thoroughly analyzed.

  9. Homogeneous alignment of liquid crystalline dendrimers confined in a slit-pore. A simulation study

    International Nuclear Information System (INIS)

    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)

  10. Ligand anchored poly(propyleneimine) dendrimers for brain targeting: Comparative in vitro and in vivo assessment.

    Science.gov (United States)

    Patel, Hemant K; Gajbhiye, Virendra; Kesharwani, Prashant; Jain, Narendra K

    2016-11-15

    The present investigation was aimed at developing various ligands-anchored dendrimers and comparing their brain targeting potential at one platform. Sialic acid (S), glucosamine (G) and concanavalin A (C) anchored poly(propyleneimine) (PPI) dendritic nanoconjugates were developed and evaluated for delivery of anti-cancer drug, paclitaxel (PTX) to the brain. MTT assay on U373MG human astrocytoma cells indicated IC50 values of 0.40, 0.65, 0.95, 2.00 and 3.50μM for PTX loaded SPPI, GPPI, CPPI, PPI formulations, and free PTX, respectively. The invivo pharmacokinetics and biodistribution studies in rats showed significantly higher accumulation of PTX in brain as compared to free PTX. The order of targeting potential of various ligands under investigation was found as sialic acid>glucosamine>concanavalin A. Thus, it can be concluded that sialic acid, glucosamine and Con A can be used as potential ligands to append PPI dendrimers for enhanced delivery of anticancer drugs to the brain for higher therapeutic outcome. PMID:27501037

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

    Science.gov (United States)

    Malý, J.; Lampová, H.; Semerádtová, A.; Štofik, M.; Kováčik, L.

    2009-09-01

    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 NaBH4 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.

  12. An Alkane-Soluble Dendrimer as Electron-Transport Layer in Polymer Light-Emitting Diodes.

    Science.gov (United States)

    Zhong, Zhiming; Zhao, Sen; Pei, Jian; Wang, Jian; Ying, Lei; Peng, Junbiao; Cao, Yong

    2016-08-10

    Polymer light-emitting diodes (PLEDs) have attracted broad interest due to their solution-processable properties. It is well-known that to achieve better performance, organic light-emitting diodes require multilayer device structures. However, it is difficult to realize multilayer device structures by solution processing for PLEDs. Because most semiconducting polymers have similar solubility in common organic solvents, such as toluene, xylene, chloroform, and chlorobenzene, the deposition of multilayers can cause layers to mix together and damage each layer. Herein, a novel semiorthogonal solubility relationship was developed and demonstrated. For the first time, an alkane-soluble dendrimer is utilized as the electron-transport layer (ETL) in PLEDs via a solution-based process. With the dendrimer ETL, the external quantum efficiency increases more than threefold. This improvement in the device performance is attributed to better exciton confinement, improved exciton energy transfer, and better charge carrier balance. The semiorthogonal solubility provided by alkane offers another process dimension in PLEDs. By combining them with water/alcohol-soluble polyelectrolytes, more exquisite multilayer devices can be fabricated to achieve high device performance, and new device structures can be designed and realized. PMID:27435357

  13. 177Lu-Dendrimer Conjugated to Folate and Bombesin with Gold Nanoparticles in the Dendritic Cavity: A Potential Theranostic Radiopharmaceutical

    Directory of Open Access Journals (Sweden)

    Héctor Mendoza-Nava

    2016-01-01

    Full Text Available 177Lu-labeled nanoparticles conjugated to biomolecules have been proposed as a new class of theranostic radiopharmaceuticals. The aim of this research was to synthesize 177Lu-dendrimer(PAMAM-G4-folate-bombesin with gold nanoparticles (AuNPs in the dendritic cavity and to evaluate the radiopharmaceutical potential for targeted radiotherapy and the simultaneous detection of folate receptors (FRs and gastrin-releasing peptide receptors (GRPRs overexpressed in breast cancer cells. p-SCN-Benzyl-DOTA was conjugated in aqueous-basic medium to the dendrimer. The carboxylate groups of Lys1Lys3(DOTA-bombesin and folic acid were activated with HATU and also conjugated to the dendrimer. The conjugate was mixed with 1% HAuCl4 followed by the addition of NaBH4 and purified by ultrafiltration. Elemental analysis (EDS, particle size distribution (DLS, TEM analysis, UV-Vis, and infrared and fluorescence spectroscopies were performed. The conjugate was radiolabeled using 177LuCl3 or 68GaCl3 and analyzed by radio-HPLC. Studies confirmed the dendrimer functionalization with high radiochemical purity (>95%. Fluorescence results demonstrated that the presence of AuNPs in the dendritic cavity confers useful photophysical properties to the radiopharmaceutical for optical imaging. Preliminary binding studies in T47D breast cancer cells showed a specific cell uptake (41.15±2.72%. 177Lu-dendrimer(AuNP-folate-bombesin may be useful as an optical and nuclear imaging agent for breast tumors overexpressing GRPR and FRs, as well as for targeted radiotherapy.

  14. Tripodal Receptors for Cation and Anion Sensors

    NARCIS (Netherlands)

    Kuswandi, Bambang; Nuriman,; Verboom, Willem; Reinhoudt, David N.

    2006-01-01

    This review discusses different types of artificial tripodal receptors for the selectiverecognition and sensing of cations and anions. Examples on the relationship between structure andselectivity towards cations and anions are described. Furthermore, their applications as potentiometricion sensing

  15. Features definition exchange cations in sedimentary rocks.

    OpenAIRE

    Bilec'ka V.A.

    2008-01-01

    The research method of determination of exchange cations in calcareous sedimentary rocks of different extractants, the influence of the ratio between the solid and liquid phases on extrusion exchange cations.

  16. Features definition exchange cations in sedimentary rocks.

    Directory of Open Access Journals (Sweden)

    Bilec'ka V.A.

    2008-05-01

    Full Text Available The research method of determination of exchange cations in calcareous sedimentary rocks of different extractants, the influence of the ratio between the solid and liquid phases on extrusion exchange cations.

  17. Preparation of unconventional dendrimers that contain rigid NH-triazine linkages and peripheral tert-butyl moieties for CO2 -selective adsorption.

    Science.gov (United States)

    Lee, Cheng-Hua; Tsai, Meng-Rong; Chang, Yen-Tzu; Lai, Long-Li; Lu, Kuang-Lieh; Cheng, Kung-Lung

    2013-08-01

    Three unconventional dendrimers that contained rigid NH-triazine linkages and peripheral tert-butyl moieties were prepared by using a convergent approach and characterized by (1)H and (13)C NMR spectroscopy, mass spectrometry, and elemental analysis. Based on a thermogravimetric analysis study, these dendrimers were observed to display thermal stability at about 300 °C. The NH-triazine moiety, which possessed protonated and proton-free nitrogen sites (like the imidazole unit), displayed the capture of polarizable CO2 molecules through hydrogen-bond and/or dipole-quadrupole interactions. In addition, the adsorption of various amounts of CO2 and N2 at different pressures suggests that the dendritic pores, which arise from the stacking of the middle co-planar and rim protuberant dendrimers, Gn -N∼N-Gn (n=1-3), either swell or shrink at high pressure, thus indicating that these dendrimers may have a breathing ability. PMID:23794529

  18. Conception de dendrimères liquides-cristallins pour la fonctionnalisation de nanoparticules d'or et de composés inorganiques et organiques

    OpenAIRE

    Frein, Stéphane; Deschenaux, Robert

    2009-01-01

    Ce travail de thèse a pour sujet principal la synthèse et la caractérisation de dendrimères liquides-cristallins. Trois dendrimères ont été synthétisés. Le premier est un dendrimère poly(aryl ester) fonctionnalisé par des unités mésogènes cyanobiphényles et qui développe des phases lamellaires ou nématique. Il a été synthétisé jusqu’à la troisième génération, avec différents groupes fonctionnels sur son coeur (thiol, disulfure, alcool, acide, alcyne). Le deuxième dendrimère synthétisé est de ...

  19. Cationic electrodepositable coating composition comprising lignin

    Science.gov (United States)

    Fenn, David; Bowman, Mark P; Zawacky, Steven R; Van Buskirk, Ellor J; Kamarchik, Peter

    2013-07-30

    A cationic electrodepositable coating composition is disclosed. The present invention in directed to a cationic electrodepositable coating composition comprising a lignin-containing cationic salt resin, that comprises (A) the reaction product of: lignin, an amine, and a carbonyl compound; (B) the reaction product of lignin, epichlorohydrin, and an amine; or (C) combinations thereof.

  20. Organometallic cation-exchanged phyllosilicates

    OpenAIRE

    Fleming, Shay

    1991-01-01

    Organotin (IV) complexes formed between 0 01 M dimethyltin dichloride solutions prepared at pH 2 6 and 4 0, and trimethyltin chloride prepared at pH 3 4, with Na- 119 montmori 1lonite clay have been characterised using Sn Mflssbauer spectroscopy, X-ray diffraction, thermogravimetric analysis and water sorption isotherms Following cation exchange, Mttssbauer spectroscopy identified two tin species in the dimethyltin (IV)-exchanged clay prepared at pH 2 6 A cis specie...

  1. PAMAM Nanoparticles Promote Acute Lung Injury by Inducing Autophagic Cell Death through the Akt-TSC2-mTOR Signaling Pathway

    Institute of Scientific and Technical Information of China (English)

    Chenggang Li; Haolin Liu; Yang Sun; Hongliang Wang; Feng Guo; Shuan Rao; Jiejie Deng; Yanli Zhang; Yufa Miao; Chenying Guo; Jie Meng; Xiping Chen; Limin Li; Dangsheng Li; Haiyan Xu; Heng Wang; Bo Li; Chengyu Jiang

    2009-01-01

    Nanotechnology is an important and emerging industry with a projected annual market of around one trillion US dollars by 2011–2015. Concerns about the toxicity of nanomaterials in humans, however, have recently been raised. Although studies of nanoparticle toxicity have focused on lung disease the molecular link between nanoparticle exposure and lung injury remained unclear. In this report, we show that cationic Starburst polyamidoamine dendrimer (PAMAM), a class of nanomaterials that are being widely developed for clinical applications can induce acute lung injury in vivo. PAMAM triggers autophagic cell death by deregulating the Akt-TSC2-mTOR signaling pathway. The autophagy inhibitor 3-methyladenine rescued PAMAM dendrimer-induced cell death and ameliorated acute lung injury caused by PAMAM in mice. Our data provide a molecular explanation for nanoparticle-induced lung injury, and suggest potential remedies to address the growing concerns of nanotechnology safety.

  2. Synthesis of Non-Cytotoxic Poly(Ester-Amine) Dendrimers as Potential Solubility Enhancers for Drugs: Methotrexate as a Case Study

    OpenAIRE

    Patricia Guadarrama; María Teresa Ramírez Apan; Jorge A. Cruz-Morales; Delia Soto-Castro

    2010-01-01

    This study describes the synthesis of two new families of dendrimers based on the esterification of N-alkylated 3-amine-1-propanol with two different cores, adipic acid (1st and 2nd generations) and ethylenediamine (generation 1.5), both with carboxylic acid end groups, offering a wide variety of further modifications at the periphery. According to the cytotoxic evaluation of the dendrimers and their possible degradation products within cell lines, these materials could be considered as innoc...

  3. Pharmacokinetics of Chiral Dendrimer-Triamine-Coordinated Gd-MRI Contrast Agents Evaluated by in Vivo MRI and Estimated by in Vitro QCM

    Directory of Open Access Journals (Sweden)

    Yuka Miyake

    2015-12-01

    Full Text Available Recently, we developed novel chiral dendrimer-triamine-coordinated Gd-MRI contrast agents (Gd-MRI CAs, which showed longitudinal relaxivity (r1 values about four times higher than that of clinically used Gd-DTPA (Magnevist®, Bayer. In our continuing study of pharmacokinetic differences derived from both the chirality and generation of Gd-MRI CAs, we found that the ability of chiral dendrimer Gd-MRI CAs to circulate within the body can be directly evaluated by in vitro MRI (7 T. In this study, the association constants (Ka of chiral dendrimer Gd-MRI CAs to bovine serum albumin (BSA, measured and calculated with a quartz crystal microbalance (QCM in vitro, were found to be an extremely easy means for evaluating the body-circulation ability of chiral dendrimer Gd-MRI CAs. The Ka values of S-isomeric dendrimer Gd-MRI CAs were generally greater than those of R-isomeric dendrimer Gd-MRI CAs, which is consistent with the results of our previous MRI study in vivo.

  4. Formation of complexes between PAMAM-NH2 G4 dendrimer and L-α-tryptophan and L-α-tyrosine in water

    Science.gov (United States)

    Buczkowski, Adam; Urbaniak, Pawel; Belica, Sylwia; Sekowski, Szymon; Bryszewska, Maria; Palecz, Bartlomiej

    2014-07-01

    Interactions between electromagnetic radiation and the side substituents of aromatic amino acids are widely used in the biochemical studies on proteins and their interactions with ligand molecules. That is why the aim of our study was to characterize the formation of complexes between PAMAM-NH2 G4 dendrimer and L-α-tryptophan and L-α-tyrosine in water. The number of L-α-tryptophan and L-α-tyrosine molecules attached to the macromolecule of PAMAM-NH2 G4 dendrimer and the formation constants of the supramolecular complexes formed have been determined. The macromolecule of PAMAM-NH2 G4 can reversibly attach about 25 L-α-tryptophan molecules with equilibrium constant K equal to 130 ± 30 and 24 ± 6 L-α-tyrosine molecules. This characterization was deduced on the basis of the solubility measurements of the amino acids in aqueous dendrimer solutions, the 1H NMR and 2D-NOESY measurements of the dendrimer solutions with the amino acids, the equilibrium dialysis and the circular dichroism measurements of the dendrimer aqueous solutions with L-α-tryptophan. Our date confirmed the interactions of L-α-tryptophan and L-α-tyrosine with the dendrimer in aqueous solution and indicated a reversible character of the formed complexes.

  5. Enhanced activity of carbosilane dendrimers against HIV when combined with reverse transcriptase inhibitor drugs: searching for more potent microbicides

    Directory of Open Access Journals (Sweden)

    Vacas-Córdoba E

    2014-07-01

    Full Text Available Enrique Vacas-Córdoba,1–3 Marta Galán,3,4 Francisco J de la Mata,3,4 Rafael Gómez,3,4 Marjorie Pion,1–3 M Ángeles Muñoz-Fernández1–3 1Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain; 2Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain; 3Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, (CIBER-BBN, Madrid, Spain; 4Dendrimers for Biomedical Applications Group (BioInDen, University of Alcalá, Madrid, Spain Abstract: Self-administered topical microbicides or oral preexposure prophylaxis could be very helpful tools for all risk groups to decrease the human immunodeficiency virus (HIV-1 infection rates. Up until now, antiretrovirals (ARVs have been the most advanced microbicide candidates. Nevertheless, the majority of clinical trials has failed in HIV-1 patients. Nanotechnology offers suitable approaches to develop novel antiviral agents. Thereby, new nanosystems, such as carbosilane dendrimers, have been shown to be safe and effective compounds against HIV with great potential as topical microbicides. In addition, because most of the attempts to develop effective topical microbicides were unsuccessful, combinatorial strategies could be a valid approach when designing new microbicides. We evaluated various combinations of anionic carbosilane dendrimers with sulfated (G3-S16 and naphthyl sulfonated (G2-NF16 ended groups with different ARVs against HIV-1 infection. The G3-S16 and G2-NF16 dendrimers showed a synergistic or additive activity profile with zidovudine, efavirenz, and tenofovir in the majority of the combinations tested against the X4 and R5 tropic HIV-1 in cell lines, as well as in human primary cells. Therefore, the combination of ARVs and polyanionic carbosilane dendrimers enhances the antiviral potency of the individual compounds, and our findings support further clinical research on combinational approaches as

  6. Targeted Theranostic Approach for Glioma Using Dendrimer-Based Curcumin Nanoparticle

    Science.gov (United States)

    Gamage, NH; Jing, Li; Worsham, MJ; Ali, MM

    2016-01-01

    The delivery of anti-cancer agents to brain tumors represent a challenge because the blood-brain tumor barrier (BBTB) effectively limits the delivery of many agents. A new generation 3 (G3) dendrimer-based curcumin (Curc) conjugate was synthesized. The synthesized G3-Curc conjugate demonstrated full solubility in aqueous media. The in vitro study revealed that G3-Curc nanoparticles were internalized into glioma U-251 cells. Systemic delivery of G3-Curc conjugate led to preferentially accumulation in an orthotopic preclinical glioma model minimizing systemic toxic effect. Multicolor microscopy images of the tumor tissue showed that G3-Curc particles were internalized inside tumor cells selectively and further localized within nuclei. Enhanced bioavailability of G3-Curc conjugate was also observed with improved therapeutic efficacy against different cancers cells. PMID:27699139

  7. Covalent immobilization of lipases on monodisperse magnetic microspheres modified with PAMAM-dendrimer

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Weiwei [Lanzhou University, State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Institute of Biochemical Engineering and Environmental Technology (China); Zhang, Yimei [Suzhou Research Academy of North China Electric Power University (China); Hou, Chen; Pan, Duo; He, Jianjun; Zhu, Hao, E-mail: zhuhao07@lzu.edu.cn [Lanzhou University, State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Institute of Biochemical Engineering and Environmental Technology (China)

    2016-02-15

    This paper reported an immobilization of Candida rugosa lipase (CRL) onto PAMAM-dendrimer-grafted magnetic nanoparticles synthesized by a modified solvothermal reduction method. The dendritic magnetic nanoparticles were amply characterized by several instrumental measurements, and the CRL was covalently anchored on the three generation supports with glutaraldehyde as coupling reagent. The amount of immobilized enzyme was up to 150 mg/g support and the factors related with the enzyme activity were investigated. The immobilization of lipase improved their performance in wider ranges of pH and temperature. The immobilized lipase exhibited excellent thermal stability and reusability in comparison with free enzyme and can be reused 10 cycles with the enzymatic activity remained above 90 %. The properties of lipase improved obviously after being immobilized on the dendritic supports. The inactive immobilized lipase could be regenerated with glutaraldehyde and Cu{sup 2+}, respectively. This synthetic strategy was facile and eco-friendly for applications in lipase immobilization.

  8. Supramolecular Assemblies of Poly(propyleneimine) Dendrimers Driven by Simple Monovalent Counterions

    Science.gov (United States)

    Eghtesadi, Seyed Ali; Haso, Fadi; Kashfipour, Marjan Alsadat; Lillard, Robert, , Dr.; Liu, Tianbo, , Dr.; Tianbo Liu's group Team, Dr.; Lillard's group Collaboration, Dr.

    Polyelectrolytes (PE) are fascinating class of polymers carrying dissociative ionic groups which give them unique properties in solutions and at charged surfaces. The properties of these polymers in solution are mainly depending on the fraction of dissociated ionic groups, the quality of solvent and salt concentration. Describing the solution properties of polyelectrolytes have always been an obstacle for polymer scientists due to their different behavior as a result of their dual character of being highly charged electrolytes and at macromolecular size. The question we tried to address was what happens to solution behavior of charged polyelectrolytes when they reach to the nano-scale size which can neither be considered as point charges nor colloids. Second generation of poly(propyleneimine) dendrimer in different solvent qualities, salt concentrations, pH and temperatures were studied using techniques such as LLS, TEM, AFM and zeta-potential, and dominant controlling factors over their self-assembly into hollow spherical ``Blackberry'' like nanoparticles was investigated.

  9. Non-adiabatic excited state molecular dynamics of phenylene ethynylene dendrimer using a multiconfigurational Ehrenfest approach.

    Science.gov (United States)

    Fernandez-Alberti, Sebastian; Makhov, Dmitry V; Tretiak, Sergei; Shalashilin, Dmitrii V

    2016-04-21

    Photoinduced dynamics of electronic and vibrational unidirectional energy transfer between meta-linked building blocks in a phenylene ethynylene dendrimer is simulated using a multiconfigurational Ehrenfest in time-dependent diabatic basis (MCE-TDDB) method, a new variant of the MCE approach developed by us for dynamics involving multiple electronic states with numerous abrupt crossings. Excited-state energies, gradients and non-adiabatic coupling terms needed for dynamics simulation are calculated on-the-fly using the Collective Electron Oscillator (CEO) approach. A comparative analysis of our results obtained using MCE-TDDB, the conventional Ehrenfest method and the surface-hopping approach with and without decoherence corrections is presented. PMID:27004611

  10. Nanoparticle corona for proteins: mechanisms of interaction between dendrimers and proteins.

    Science.gov (United States)

    Shcharbin, Dzmitry; Ionov, Maksim; Abashkin, Viktar; Loznikova, Svetlana; Dzmitruk, Volha; Shcharbina, Natallia; Matusevich, Ludmila; Milowska, Katarzyna; Gałęcki, Krystian; Wysocki, Stanisław; Bryszewska, Maria

    2015-10-01

    Protein absorption at the surface of big nanoparticles and formation of 'protein corona' can completely change their biological properties. In contrast, we have studied the binding of small nanoparticles - dendrimers - to proteins and the formation of their 'nanoparticle corona'. Three different types of interactions were observed. (1) If proteins have rigid structure and active site buried deeply inside, the 'nanoparticle corona' is unaffected. (2) If proteins have a flexible structure and their active site is also buried deeply inside, the 'nanoparticle corona' affects protein structure, but not enzymatic activity. (3) The 'nanoparticle corona' changes both the structure and enzymatic activity of flexible proteins that have surface-based active centers. These differences are important in understanding interactions taking place at a bio-nanointerface.

  11. 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.

  12. The synthesis and adsorption properties of some carbohydrate-terminated dendrimer wedges

    CERN Document Server

    Ainsworth, R L

    1997-01-01

    A range of dendritic molecules that are designed to bind to a cotton surface has been synthesised. The architecture of the molecules allows the location of various functional, property modifying units at the focus and the attachment of recognition groups at the periphery of a dendritic molecule with wedge topology. The synthesis and characterisation of dendrimer wedges up to the second generation using a divergent approach has been performed. These wedges are readily built up using a simple and efficient stepwise pathway from the central core, and surface recognising species are subsequently attached to the molecule utilising procedures developed in conjunction with Unilever Research Laboratories. Work has been carried out to assess their adsorption onto a cotton surface and the postulated adsorption mechanism is discussed.

  13. HIV-1 antiviral behavior of anionic PPI metallo-dendrimers with EDA core.

    Science.gov (United States)

    García-Gallego, Sandra; Díaz, Laura; Jiménez, José Luis; Gómez, Rafael; de la Mata, F Javier; Muñoz-Fernández, M Ángeles

    2015-06-15

    The development of novel strategies to prevent HIV-1 infection is of outstanding relevance. Metal complexes of Cu(2+), Ni(2+), Co(2+) and Zn(2+) derived from sulfonated and carboxylated poly(propylene imine) dendrimers with ethylenediamine core were evaluated as tunable antiviral agents against HIV-1. After demonstrating their biocompatibility, specific trends in the antiviral properties were found, related to both the dendritic scaffold (peripheral group, generation) and the bound metal ions (sort, amount). In HEC-1A and VK-2 cell lines, as model of the first barrier against HIV-1 infection, a high preventive inhibitory action was found, which also avoided virus internalization inside cells and inhibited both CCR5 and CXCR4 HIV-1 strains. In peripheral blood mononuclear cells (PBMC), as model of the second barrier, a dual preventive and therapeutic behavior was observed. A rational design of such metallodendrimers opens new avenues for the production of versatile and efficient treatments against HIV-1 infection. PMID:26005027

  14. Folate Receptor-Targeted Dendrimer-Methotrexate Conjugate for Inflammatory Arthritis.

    Science.gov (United States)

    Qi, Rong; Majoros, Istvan; Misra, Asish C; Koch, Alisa E; Campbell, Phil; Marotte, Hubert; Bergin, Ingrid L; Cao, Zhengyi; Goonewardena, Sascha; Morry, Jingga; Zhang, Shuai; Beer, Michael; Makidon, Paul; Kotlyar, Alina; Thomas, Thommey P; Baker, James R

    2015-08-01

    Generation 5 (G5) poly(amidoamide) (PAMAM) dendrimers are synthetic polymers that have been broadly applied as drug delivery carriers. Methotrexate (MTX), an anti-folate metabolite, has been successfully used as an anti-inflammatory drug to treat rheumatoid arthritis (RA) in the clinic. In this study, we examine the therapeutic efficacy of G5 PAMAM dendrimer methotrexate conjugates (G5-MTX) that also have folic acid (FA) conjugated to the G5-MTX (G5-FA-MTX) to target inflammation-activated folate receptors overexpressing macrophages. These cells are thought to play an important role in the development of RA. With G5 serving as a control, the in vitro binding affinities of G5-FA-MTX and G5-MTX to activated macrophages were assessed in RAW264.7, NR8383 and primary rat peritoneal macrophages. The results indicated that the binding of either conjugate to macrophages was concentration- and temperature-dependent and could be blocked by the presence of 6.25 mM free FA (p < 0.005). The preventive effects of G5-MTX and G5-FA-MTX conjugates on the development of arthritis were explored on an adjuvant-induced inflammatory arthritis model and had similar preventive effects in inflammatory arthritis at a MTX equivalent dose of 4.95 μmol/kg. These studies indicated that when multiples of MTX are conjugated on dendritic polymers, they specifically bind to folate receptor overexpressing macrophages and have comparable anti-inflammatory effects to folate targeted MTX conjugated polymers.

  15. Low generation polyamine dendrimers bearing flexible tetraethylene glycol as nanocarriers for plasmids and siRNA

    Science.gov (United States)

    Sharma, Rishi; Zhang, Issan; Shiao, Tze Chieh; Pavan, Giovanni M.; Maysinger, Dusica; Roy, René

    2016-02-01

    Low G1 generation polyamine dendrimers built around programmable, flexible, and short tetraethyleneglycol branches were readily prepared in a divergent manner using a combination of orthogonal AB3 or AB5 units and highly efficient chemical transformations based on Cu(i) catalyzed alkyne-azide cycloaddition (CUAAC) and thiol-ene click reactions. The constructs showed that the G1 polyamines with only twelve and eighteen amine surface groups can successfully deliver siRNA in human cells, with transfection efficiency comparable to that of Lipofectamine 2000®. Measurements of cell viability following transfection of plasmid DNA and siRNA showed that the dendritic polyamines are less cytotoxic than Lipofectamine 2000® and are thus preferable for biological applications.Low G1 generation polyamine dendrimers built around programmable, flexible, and short tetraethyleneglycol branches were readily prepared in a divergent manner using a combination of orthogonal AB3 or AB5 units and highly efficient chemical transformations based on Cu(i) catalyzed alkyne-azide cycloaddition (CUAAC) and thiol-ene click reactions. The constructs showed that the G1 polyamines with only twelve and eighteen amine surface groups can successfully deliver siRNA in human cells, with transfection efficiency comparable to that of Lipofectamine 2000®. Measurements of cell viability following transfection of plasmid DNA and siRNA showed that the dendritic polyamines are less cytotoxic than Lipofectamine 2000® and are thus preferable for biological applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06757j

  16. Regulatory activity of azabisphosphonate-capped dendrimers on human CD4+ T cell proliferation enhances ex-vivo expansion of NK cells from PBMCs for immunotherapy

    Directory of Open Access Journals (Sweden)

    Caminade Anne-Marie

    2009-09-01

    Full Text Available Abstract Background Adoptive cell therapy with allogenic NK cells constitutes a promising approach for the treatment of certain malignancies. Such strategies are currently limited by the requirement of an efficient protocol for NK cell expansion. We have developed a method using synthetic nanosized phosphonate-capped dendrimers allowing such expansion. We are showing here that this is due to a specific inhibitory activity towards CD4+ T cell which could lead to further medical applications of this dendrimer. Methods Mononuclear cells from human peripheral blood were used to investigate the immunomodulatory effects of nanosized phosphonate-capped dendrimers on interleukin-2 driven CD4+T cell expansion. Proliferation status was investigated using flow cytometry analysis of CFSE dilution and PI incorporation experiments. Magnetic bead cell sorting was used to address activity towards individual or mixed cell sub-populations. We performed equilibrium binding assay to assess the interaction of fluorescent dendrimers with pure CD4+ T cells. Results Phosphonate-capped dendrimers are inhibiting the activation, and therefore the proliferation; of CD4+ T cells in IL-2 stimulated PBMCs, without affecting their viability. This allows a rapid enrichment of NK cells and further expansion. We found that dendrimer acts directly on T cells, as their regulatory property is maintained when stimulating purified CD4+ T cells with anti-CD3/CD28 microbeads. Performing equilibrium binding assays using a fluorescent analogue, we show that the phosphonate capped-dendrimers are specifically interacting with purified CD4+ T cells. Ultimately, we found that our protocol prevents the IL-2 related expansion of regulatory T cells that would be deleterious for the activity of infused NK cells. Conclusion High yield expansion of NK cells from human PBMCs by phosphonate-capped dendrimers and IL-2 occurs through the specific inhibition of the CD4+ lymphocyte compartment. Given the

  17. Use of laser induced photoacoustic spectroscopy (LIPAS) to determine equilibrium constants of cation-cation complexes

    International Nuclear Information System (INIS)

    Laser Induced PhotoAcoustic Spectroscopy (LIPAS) is a relatively new, photothermal technique to examine solutions. Studies in the past have shown it to be more sensitive than conventional absorption spectroscopy, while, yielding the same information thus allowing lower concentrations to be used. This study is using LIPAS to examine solutions to determine the equilibrium constants of cation-cation complexes. It has been found that actinyl(V) cations form cation-cation complexes with a variety of cations, including actinyl(VI) cations. The radioactive nature of the actinide elements requires special handling techniques and also require limits be placed on the amount of material that can be used. The sensitivity of some oxidation states of the actinides to oxygen also presents a problem. Preliminary results will be presented for actinyl(V)-actinyl(VI) cation-cation complexes that were studied using a remote LIPAS system incorporating fiber optics for transmission of laser signals

  18. The Free Tricoordinated Silyl Cation Problem

    Directory of Open Access Journals (Sweden)

    Čičak, H.

    2010-03-01

    Full Text Available As the importance and abundance of silicon in our environment is large, it has been thought that silicon might take the place of carbon in forming a host of similar compounds and silicon-based life. However, until today there is no experimental evidence for such a hypothesis and carbon is still unique among the elements in the vast number and variety of compounds it can form. Also, the corresponding derivatives of the two elements show considerable differences in their chemical properties.The essential debate concerning organosilicon chemistry relates to the existence of the free planar tricoordinated silyl cations in condensed phase (R3Si+, in analogy to carbocations (R3C+ which have been known and characterized as free species. Although silyl cations are thermodynamically more stable than their carbon analogs, they are very reactive due to their high inherent electrophilicity and the ability of hypervalent coordination. On the other hand, stabilization by inductive and hyperconjugative effects and larger steric effects of carbocations make them less sensitive to solvation or other environmental effects than silyl cations. Hence, observation of free silyl cations in the condensed phase proved extremely difficult and the actual problem is the question of the degree of the (remaining silyl cation character.The first free silyl cation, trimesitylsilyl cation, and in analogy with it tridurylsilyl cation, were synthesized by Lambert et al. Free silyl cations based on analogy to aromatic ions (homocyclopropenylium and tropylium have also been prepared. However, in these silyl cations the cationic character is reduced by internal π -conjugation. Čičak et al. prepared some silyl-cationic intermediates (Me3Si--CH≡CR+in solid state. With the help of quantum-mechanical calculations it was concluded that these adducts have much more silyl cation than carbocation character.

  19. 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.

  20. A Facile Strategy to Prepare Dendrimer-stabilized Gold Nanorods with Sub-10-nm Size for Efficient Photothermal Cancer Therapy

    Science.gov (United States)

    Wang, Xinyu; Wang, Hanling; Wang, Yitong; Yu, Xiangtong; Zhang, Sanjun; Zhang, Qiang; Cheng, Yiyun

    2016-03-01

    Gold (Au) nanoparticles are promising photothermal agents with the potential of clinical translation. However, the safety concerns of Au photothermal agents including the potential toxic compositions such as silver and copper elements in their structures and the relative large size-caused retention and accumulation in the body post-treatment are still questionable. In this article, we successfully synthesized dendrimer-stabilized Au nanorods (DSAuNRs) with pure Au composition and a sub-10-nm size in length, which represented much higher photothermal effect compared with dendrimer-encapsulated Au nanoparticles due to their significantly enhanced absorption in the near-infrared region. Furthermore, glycidol-modified DSAuNRs exhibited the excellent biocompatibility and further showed the high photothermal efficiency of killing cancer cells in vitro and retarding tumor growth in vivo. The investigation depicted an optimal photothermal agent with the desirable size and safe composition.

  1. The effect of polyethylene glycol spacer chain length on the tumor-targeting potential of folate-modified PPI dendrimers

    Energy Technology Data Exchange (ETDEWEB)

    Thakur, Shrikant [Dr. Hari Singh Gour University, Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences (India); Tekade, Rakesh K., E-mail: rakeshtekade@yahoo.com [University of Hawai' i at Hilo, College of Pharmacy (United States); Kesharwani, Prashant, E-mail: prashant_pharmacy04@rediffmail.com; Jain, Narendra K., E-mail: jnarendr@yahoo.co.in [Dr. Hari Singh Gour University, Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences (India)

    2013-05-15

    The objective of the present investigation was to assess the tumor-targeting potential of ligand-spacer-engineered poly (propylene imine) (PPI) dendrimers as nanoscale drug delivery units for site-specific delivery of a model anticancer agent, docetaxel (DTX). PPI dendrimers were engineered by direct and indirect conjugation of folic acid (FA) via different types of polyethylene glycols (PEGs) [Mw (molecular weight): 1,000, 4,000, 6,000, 7,500] as spacers. The synthesized nanoconjugates (PPIFA, PPIP1FA, PPIP4FA, PPIP6FA, and PPIP7.5FA) were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance ({sup 1}H-NMR) and transmission electron microscopic (TEM) studies. Nanoconjugates were evaluated for entrapment, in vitro drug release (under various pH conditions) and hemolytic studies. Cell uptake and cytotoxicity studies were performed on human malignant cell lines (MCF-7) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide [MTT] assay. This debut study explored the effect of PEG spacer length on the targeting potential of folate-conjugated 5.0 G PPI dendrimer. DTX entrapment and in vitro drug release from nanoconjugates augmented, and hemolytic toxicity of nanoconjugates slashed with the molecular weight of PEGs. Further, nanoconjugates with PEG 4000 displayed highest tumor-targeting potential as compared to other spacer conjugated nanoconjugates due to optimized steric hindrance and receptor mediated endocytosis among other PEGs. This work is expected to shed new light on the role of spacer chain length in targeting potential of folate-anchored dendrimer.Graphical Abstract.

  2. Preparation of dendrimer funcationalized carbon nanotube/Pd nanoparticles composite for nonenzymatic glucose biosensing%树状聚合物功能化碳纳米管/钯纳米复合物的制备及其非酶葡萄糖传感应用

    Institute of Scientific and Technical Information of China (English)

    侯代红; 赖国松; 张海丽

    2014-01-01

    Polyamidoamine (PAMAM) dendrimer was covalently grafted with carboxylated carbon nanotubes (CNTs) for the in situ deposition of palladium nanoparticles (Pd NPs).Based on the electrode modification with the as -prepared CNTs-PAM-AM/Pd NPs nanocomposites and the further coating of chitosan on its surface , a nonenzymatic amperometric glucose biosensor was developed.Electrochemical impedance spectroscopy and cyclic voltammetry were used to characterize and optimize the performance of the sensor.Under the optimal conditions, this sensor exhibited a rapid amperometric response towards glucose (less than 3 s), and a wide linear range from 0.03 to 61.7 m mol・ L-1 was obtained with a detection limit of 11.5μmol・L-1 (S/N=3).This biosensor has low cost , good stability, selectivity and repeatability, thus indicating great potentials for practical applications.%将树状聚合物(PAMAM)通过共价反应嫁接在羧基化碳纳米管(CNTs)表面后用于钯纳米粒子(Pd NPs)的原位沉积,制备成CNTs-PAMAM/Pd NPs复合物。通过壳聚糖包埋将制备的该钯纳米复合物用于玻碳电极的修饰,并通过交流阻抗法和循环伏安法对电极性能进行表征和优化,制备成可用于葡萄糖的安培检测的非酶电化学传感器。实验表明,在最佳实验条件下该传感器可在较短时间内(<3 s)实现对葡萄糖的快速稳态安培响应,并可在从0.03 mmol/L至61.7 mmol/L较宽线性范围内实现对葡萄糖的准确测定,检出限为11.5μmol/L。该传感器成本低廉,性质稳定,且具有较好的选择性和重复性,因而在实际应用中具有较好的发展前景。

  3. Mastering Dendrimer Self-Assembly for Efficient siRNA Delivery: From Conceptual Design to In Vivo Efficient Gene Silencing.

    Science.gov (United States)

    Chen, Chao; Posocco, Paola; Liu, Xiaoxuan; Cheng, Qiang; Laurini, Erik; Zhou, Jiehua; Liu, Cheng; Wang, Yang; Tang, Jingjie; Col, Valentina Dal; Yu, Tianzhu; Giorgio, Suzanne; Fermeglia, Maurizio; Qu, Fanqi; Liang, Zicai; Rossi, John J; Liu, Minghua; Rocchi, Palma; Pricl, Sabrina; Peng, Ling

    2016-07-01

    Self-assembly is a fundamental concept and a powerful approach in molecular science. However, creating functional materials with the desired properties through self-assembly remains challenging. In this work, through a combination of experimental and computational approaches, the self-assembly of small amphiphilic dendrons into nanosized supramolecular dendrimer micelles with a degree of structural definition similar to traditional covalent high-generation dendrimers is reported. It is demonstrated that, with the optimal balance of hydrophobicity and hydrophilicity, one of the self-assembled nanomicellar systems, totally devoid of toxic side effects, is able to deliver small interfering RNA and achieve effective gene silencing both in cells - including the highly refractory human hematopoietic CD34(+) stem cells - and in vivo, thus paving the way for future biomedical implementation. This work presents a case study of the concept of generating functional supramolecular dendrimers via self-assembly. The ability of carefully designed and gauged building blocks to assemble into supramolecular structures opens new perspectives on the design of self-assembling nanosystems for complex and functional applications. PMID:27244195

  4. Synthesis of Dendrimer-supported Chiral Bis(oxazoline) Ligands and Their Applications in Aldol Reaction via Aqueous Media

    Institute of Scientific and Technical Information of China (English)

    CHEN Xiao-min; YANG Bai-yuan; ZHANG Yi-li; QU Xue; FAN Qing-hua

    2004-01-01

    Chiral bis(oxazoline) ligands have been applied in many enatioselective reactions.Recently, studies of the immobilization of bis(oxazoline) on both soluble and insoluble supports have been of great interest. Among the different methods to anchor the homogeneous catadysts, a soluble, polymer-supported catalyst usually achieves higher stereoselectivity and activity because the catalysis can be separated and recycled via simple methods such as solvent precipitation.Dendrimers are highly branched macromolecules having precisely defined molecular structures with nano-scale size. Compared with soluble polymer supports, the dendrimer architecture may offer better control of the deposition of the catalytic species in soluble polymer-based catalysts. Therefore,such catalysts may fill the gap between homogeneous and heterogeneous catalysis and combine the advantages of both.In this paper, we report the synthesis of bis(oxazoline)-centered dendrimers and their application in Mukaiyama aldol reaction in aqueous media. It was found that the dendritic chiral bis(oxazolines)showed the similar reactivities and enantioselectivities in the asymmetric copper-catalyzed aldol reaction in aqueous media in comparison to the corresponding small molecular ligands.

  5. Vibrational spectra study of fluorescent dendrimers built from the cyclotriphosphazene core with terminal dansyl and carbamate groups

    Science.gov (United States)

    Furer, V. L.; Vandyukova, I. I.; Vandyukov, A. E.; Fuchs, S.; Majoral, J. P.; Caminade, A. M.; Kovalenko, V. I.

    2011-08-01

    The FTIR and FT Raman spectra of the "Janus"-type dendrimers, possessing five carbamate groups on one side and five fluorescent dansyl derivatives on the other side, with amide G1 and hydrazone G2 central linkages were studied. These surface-block dendrimers are obtained by the coupling of two different dendrons. The FTIR and FT-Raman spectra of the zero generation dendrons, built from the hexafunctional cyclotriphosphazene core, with five dansyl terminal groups and one carbamate G0 v and one oxybenzaldehyde function G0v have been recorded. The structural optimization and normal mode analysis were performed for dendron G0v on the basis of the density functional theory (DFT). The calculated geometrical parameters and harmonic vibrational frequencies are predicted in a good agreement with the experimental data. It was found that dendron molecule G0v has a concave lens structure with planar -O-C6H4-CHdbnd O fragments and slightly non-planar cyclotriphosphazene core. The experimental IR and Raman spectra of dendron G0v were interpreted by means of potential energy distributions. Relying on DFT calculations a complete vibrational assignment is proposed. The strong band 1597 cm -1 show marked changes of the optical density in dependence of substituents in the aromatic ring. The frequencies of ν(N-H) bands in the IR spectra reveal the presence of the different types of H-bonds in the dendrimers.

  6. Functionalization of a Triazine Dendrimer Presenting Four Maleimides on the Periphery and a DOTA Group at the Core.

    Science.gov (United States)

    Lee, Changsuk; Ji, Kun; Simanek, Eric E

    2016-01-01

    A readily and rapidly accessible triazine dendrimer was manipulated in four steps with 23% overall yield to give a construct displaying four maleimide groups and DOTA. The maleimide groups of the dendrimer are sensitive to hydrolysis under basic conditions. The addition of up to four molecules of water can be observed via mass spectrometry and HPLC. The evolution in the alkene region of the ¹H-NMR--the transformation of the maleimide singlet to the appearance of two doublets--is consistent with imide hydrolysis and not the Michael addition. The hydrolysis events that proceeded over hours are sufficiently slower than the desired thiol addition reactions that occur in minutes. The addition of thiols to maleimides can be accomplished in a variety of solvents. The thiols examined derived from cysteine and include the protected amino acid, a protected dipeptide, and native oligopeptides containing either 9 or 18 amino acids. The addition reactions were monitored with HPLC and mass spectrometry in most cases. Complete substitution was observed for small molecule reactants. The model peptides containing nine or eighteen amino acids provided a mixture of products averaging between 3 and 4 substitutions/dendrimer. The functionalization of the chelate group with gadolinium was also accomplished easily. PMID:26978338

  7. Afrikaans Syllabification Patterns

    Directory of Open Access Journals (Sweden)

    Tilla Fick

    2010-01-01

    Full Text Available In contrast to English, automatic hyphenation by computer of Afrikaans words is a problem that still needs to be addressed, since errors are still often encountered in printed text. An initial step in this task is the ability to automatically syllabify words. Since new words are created continuously by joining words, it is necessary to develop an “intelligent” technique for syllabification. As a first phase of the research, we consider only the orthographic information of words, and disregard both syntactic and morphological information. This approach allows us to use machine-learning techniques such as artificial neural networks and decision trees that are known for their pattern recognition abilities. Both these techniques are trained with isolated patterns consisting of input patterns and corresponding outputs (or targets that indicate whether the input pattern should be split at a certain position, or not. In the process of compiling a list of syllabified words from which to generate training data for the  syllabification problem, irregular patterns were identified. The same letter patterns are split differently in different words and complete words that are spelled identically are split differently due to meaning. We also identified irregularities in and between  the different dictionaries that we used. We examined the influence range of letters that are involved in irregularities. For example, for their in agter-ente and vaste-rente we have to consider three letters to the left of r to be certain where the hyphen should be inserted. The influence range of the k in verstek-waarde and kleinste-kwadrate is four to the left and three to the right. In an analysis of letter patterns in Afrikaans words we found that the letter e has the highest frequency overall (16,2% of all letters in the word list. The frequency of words starting with s is the highest, while the frequency of words ending with e is the highest. It is important to

  8. Localization versus delocalization in diamine radical cations

    DEFF Research Database (Denmark)

    Brouwer, A.M.; Wiering, P.G.; Zwier, J.M.;

    1997-01-01

    The optical absorption spectrum of the radical cation of 1,4-diphenylpiperazine 2a shows a strong transition in the near-IR, and only a weak band at 445 nm, in the region where aniline radical cations normally absorb strongly. This indicates that the charge and spin are delocalized over the two...

  9. Tripodal Receptors for Cation and Anion Sensors

    Directory of Open Access Journals (Sweden)

    David N. Reinhoudt

    2006-08-01

    Full Text Available This review discusses different types of artificial tripodal receptors for the selectiverecognition and sensing of cations and anions. Examples on the relationship between structure andselectivity towards cations and anions are described. Furthermore, their applications as potentiometricion sensing are emphasised, along with their potential applications in optical sensors or optodes.

  10. Cationic Bolaamphiphiles for Gene Delivery

    Science.gov (United States)

    Tan, Amelia Li Min; Lim, Alisa Xue Ling; Zhu, Yiting; Yang, Yi Yan; Khan, Majad

    2014-05-01

    Advances in medical research have shed light on the genetic cause of many human diseases. Gene therapy is a promising approach which can be used to deliver therapeutic genes to treat genetic diseases at its most fundamental level. In general, nonviral vectors are preferred due to reduced risk of immune response, but they are also commonly associated with low transfection efficiency and high cytotoxicity. In contrast to viral vectors, nonviral vectors do not have a natural mechanism to overcome extra- and intracellular barriers when delivering the therapeutic gene into cell. Hence, its design has been increasingly complex to meet challenges faced in targeting of, penetration of and expression in a specific host cell in achieving more satisfactory transfection efficiency. Flexibility in design of the vector is desirable, to enable a careful and controlled manipulation of its properties and functions. This can be met by the use of bolaamphiphile, a special class of lipid. Unlike conventional lipids, bolaamphiphiles can form asymmetric complexes with the therapeutic gene. The advantage of having an asymmetric complex lies in the different purposes served by the interior and exterior of the complex. More effective gene encapsulation within the interior of the complex can be achieved without triggering greater aggregation of serum proteins with the exterior, potentially overcoming one of the great hurdles faced by conventional single-head cationic lipids. In this review, we will look into the physiochemical considerations as well as the biological aspects of a bolaamphiphile-based gene delivery system.

  11. Direct label free ultrasensitive impedimetric DNA biosensor using dendrimer functionalized GaN nanowires.

    Science.gov (United States)

    Sahoo, Prasana; Suresh, Sumathi; Dhara, Sandip; Saini, Garima; Rangarajan, S; Tyagi, A K

    2013-06-15

    We demonstrate a very simple and generic protocol for ultrasensitive in-situ label-free detection of DNA hybridization using third generation poly(amidoamine)dendrimer (G3-PAMAM) functionalized GaN nanowires (NWs). PAMAM modified GaN NWs provides large density of docking site to immobilize significant number of probe (p-) DNA covalently. These p-DNA/PAMAM/GaN NWs sensor probes are employed to achieve an ultra-high detection limit down to attomolar level concentration of complementary target (t-) DNA. Comparative in-situ studies on single/triple base-pair mismatched, γ-irradiated and complementary t-DNA in the hybridization process reveal selectivity and specificity of the p-DNA/PAMAM/GAN NWs sensor probe over a wide range, 10(-8) to 10(-19)M, of analyte concentration. During the hybridization process, there is a substantial change in t-DNA concentration dependent interfacial polarization resistance during electrochemical impedance measurement, which forms the basis of the present DNA biosensor. This novel methodology for specific DNA sequence detection, as compared with the existing methods, is found to be very robust, highly sensitive, and reproducible. PMID:23425555

  12. Detection of TNT using a sensitive two-photon organic dendrimer for remote sensing

    International Nuclear Information System (INIS)

    There is currently a need for superior stand-off detection schemes for protection against explosive weapons of mass destruction. Fluorescence detection at small distances from the target has proven to be attractive. A novel unexplored route in fluorescence chemical sensing that utilizes the exceptional spectroscopic capabilities of nonlinear optical methods is two-photon excited fluorescence. This approach utilizes infra-red light for excitation of remote sensors. Infra-red light suffers less scattering in porous materials which is beneficial for vapor sensing and has greater depth of penetration through the atmosphere, and there are fewer concerns regarding eye safety in remote detection schemes. We demonstrate this method using a novel dendritic system which possesses both excellent fluorescence sensitivity to the presence of TNT with infra-red pulses of light and high two-photon absorption (TPA) response. This illustrates the use of TPA for potential stand-off detection of energetic materials in the infra-red spectral regions in a highly two-photon responsive dendrimer

  13. Dendrimer Molecules:A Short Profile%树形大分子研究进展

    Institute of Scientific and Technical Information of China (English)

    李振江

    2001-01-01

    综述了树形大分子研究进展,介绍了树形大分子的合成及策略,讨论了树形大分子的结构特征,指出了树形大分子的理论及应用前景.对树形大人子的述语规范,树形大分子的结构层次划分的核(core)-本体(mantle)-表层(shell)的概念以及三个结构层次间的关系,和收敛合成法中的"瓣"(lobe)的概念和应用等进行了讨论.%The synthesis,structrue,tbeoretical and practival prospects,as well as the research his-tory of dendrimer molecules(DM)were reviewed briefly.The concepts concerning the bierarchi-cal structure of DM in three lcvels:I)core(C);ii)mantle(M);and iii)ahell(S),the idea of LOBE in convergent synthesis strategy,and the terminology of Dmin literature ware discussed.

  14. Cationic ruthenium alkylidene catalysts bearing phosphine ligands

    OpenAIRE

    Endo, Koji; Grubbs, Robert H.

    2016-01-01

    The discovery of highly active catalysts and the success of ionic liquid immobilized systems have accelerated attention to a new class of cationic metathesis catalysts. We herein report the facile syntheses of cationic ruthenium catalysts bear-ing bulky phosphine ligands. Simple ligand exchange using silver(I) salts of non-coordinating or weakly coordinating anions pro-vided either PPh3 or chelating Ph2P(CH2)nPPh2 (n = 2 or 3) ligated cationic catalysts. The structures of these newly reported...

  15. Composite polyester membranes with embedded dendrimer hosts and bimetallic Fe/Ni nanoparticles: synthesis, characterisation and application to water treatment

    Energy Technology Data Exchange (ETDEWEB)

    Malinga, S. P., E-mail: sitholespr@yahoo.com; Arotiba, O. A. [University of Johannesburg, Department of Applied Chemistry (South Africa); Krause, R. W. M. [Rhodes University, Department of Chemistry (South Africa); Mapolie, S. F. [University of Stellenbosch, Department of Chemistry and Polymer Science (South Africa); Diallo, M. S. [Graduate School of EEWS, Korea Advanced Institute of Science and Technology (KAIST) (Korea, Republic of); Mamba, B. B., E-mail: bmamba@uj.ac.za [University of Johannesburg, Department of Applied Chemistry (South Africa)

    2013-06-15

    This study describes the preparation, characterization and evaluation of new composite membranes with embedded dendrimer hosts and Fe/Ni nanoparticles. These new reactive membranes consist of films of cyclodextrin-poly(propyleneimine) dendrimers ({beta}-CD-PPI) that are deposited onto commercial polysulfone microporous supports and crosslinked with trimesoyl chloride (TMC). The membranes were subsequently loaded with Fe/Ni nanoparticles and evaluated as separation/reactive media in aqueous solutions using 2,4,6-trichlorophenol as model pollutant. The morphology and physicochemical properties of the composite membranes were characterised using high-resolution transmission electron microscopy (HR-TEM), atomic force microscopy and measurements of contact angle, water intake, porosity and water permeability. The sorption capacity and catalytic activity of the membranes were evaluated using ion chromatography, atmospheric pressure chemical ionisation-mass spectrometry and UV-Vis spectroscopy (UV-Vis). The sizes of the embedded Fe/Ni nanoparticles in the membranes ranged from 40 to 66 nm as confirmed by HR-TEM. The reaction rates for the dechlorination of 2,4,6-trichlorophenol ranged from 0.00148 to 0.00250 min{sup -1}. In all cases, we found that the reaction by-products consisted of chloride ions and mixtures of compounds including phenol (m/z = 93), 2,4-dichlorophenol (m/z = 163) and 4-chlorophenol (m/z = 128). The overall results of this study suggest that {beta}-CD-PPI dendrimers are promising building blocks for the synthesis of composite and reactive membranes for the efficient removal of chlorinated organic pollutants from water.

  16. Development of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides

    Science.gov (United States)

    Briz, Verónica; Sepúlveda-Crespo, Daniel; Diniz, Ana Rita; Borrego, Pedro; Rodes, Berta; de La Mata, Francisco Javier; Gómez, Rafael; Taveira, Nuno; Muñoz-Fernández, Mª Ángeles

    2015-08-01

    The development of topical microbicide formulations for vaginal delivery to prevent HIV-2 sexual transmission is urgently needed. Second- and third-generation polyanionic carbosilane dendrimers with a silicon atom core and 16 sulfonate (G2-S16), napthylsulfonate (G2-NS16) and sulphate (G3-Sh16) end-groups have shown potent and broad-spectrum anti-HIV-1 activity. However, their antiviral activity against HIV-2 and mode of action have not been probed. Cytotoxicity, anti-HIV-2, anti-sperm and antimicrobial activities of dendrimers were determined. Analysis of combined effects of triple combinations with tenofovir and raltegravir was performed by using CalcuSyn software. We also assessed the mode of antiviral action on the inhibition of HIV-2 infection through a panel of different in vitro antiviral assays: attachment, internalization in PBMCs, inactivation and cell-based fusion. Vaginal irritation and histological analysis in female BALB/c mice were evaluated. Our results suggest that G2-S16, G2-NS16 and G3-Sh16 exert anti-HIV-2 activity at an early stage of viral replication inactivating the virus, inhibiting cell-to-cell HIV-2 transmission, and blocking the binding of gp120 to CD4, and the HIV-2 entry. Triple combinations with tenofovir and raltegravir increased the anti-HIV-2 activity, consistent with synergistic interactions (CIwt: 0.33-0.66). No vaginal irritation was detected in BALB/c mice after two consecutive applications for 2 days with 3% G2-S16. Our results have clearly shown that G2-S16, G2-NS16 and G3-Sh16 have high potency against HIV-2 infection. The modes of action confirm their multifactorial and non-specific ability, suggesting that these dendrimers deserve further studies as potential candidate microbicides to prevent vaginal/rectal HIV-1/HIV-2 transmission in humans.

  17. VivaGel™ (SPL7013 Gel): A candidate dendrimer – microbicide for the prevention of HIV and HSV infection

    Science.gov (United States)

    Rupp, Richard; Rosenthal, Susan L; Stanberry, Lawrence R

    2007-01-01

    Microbicides are compounds that applied vaginally or rectally, protect the user from sexually transmitted infections. Although no commercial product is yet available, many candidates are under development. A leading candidate, VivaGel™ (SPL7013 Gel) is the product of nanotechnology. The active ingredient is SPL7013, a dendrimer that was designed specifically with HIV and HSV antiviral activity and human safety in mind. SPL7013 has demonstrated efficacy against human immunodeficiency virus and herpes simplex virus in in vitro and animal models. VivaGel™ appears to be well tolerated in both animals and humans. This review summarizes the studies of VivaGel™ and its active ingredient, SPL7013. PMID:18203424

  18. Synthesis, spectral characterization, electron microscopic study and thermogravimetric analysis of a phosphorus containing dendrimer with diphenylsilanediol as core unit

    Directory of Open Access Journals (Sweden)

    E. Dadapeer

    2010-08-01

    Full Text Available A phosphorus containing dendrimer with a diphenylsilanediol core was synthesized using a divergent method. Several types of reactions were performed on dendrons of several sizes, either at the level of the core or the surface. The giant Schiff’s base macro molecule possesses 12 imine bonds and 8 hydroxy groups on the terminal phenyl groups. The structures of the intermediate compounds were confirmed by IR, GCMS and 31P NMR. The final compound was characterized by 1H, 13C, 31P NMR, MALDI-TOF MS and CHN analysis. Scanning electron microscopic and thermogravimetric analysis/differential scanning calorimetric studies were also performed on the final dendritic molecule.

  19. Cation locations and dislocations in zeolites

    Science.gov (United States)

    Smith, Luis James

    The focus of this dissertation is the extra-framework cation sites in a particular structural family of zeolites, chabazite. Cation sites play a particularly important role in the application of these sieves for ion exchange, gas separation, catalysis, and, when the cation is a proton, acid catalysis. Structural characterization is commonly performed through the use of powder diffraction and Rietveld analysis of powder diffraction data. Use of high-resolution nuclear magnetic resonance, in the study of the local order of the various constituent nuclei of zeolites, complements well the long-range order information produced by diffraction. Recent developments in solid state NMR techniques allow for increased study of disorder in zeolites particularly when such phenomena test the detection limits of diffraction. These two powerful characterization techniques, powder diffraction and NMR, offer many insights into the complex interaction of cations with the zeolite framework. The acids site locations in SSZ-13, a high silica chabazite, and SAPO-34, a silicoaluminophosphate with the chabazite structure, were determined. The structure of SAPO-34 upon selective hydration was also determined. The insensitivity of X-rays to hydrogen was avoided through deuteration of the acid zeolites and neutron powder diffraction methods. Protons at inequivalent positions were found to have different acid strengths in both SSZ-13 and SAPO-34. Other light elements are incorporated into zeolites in the form of extra-framework cations, among these are lithium, sodium, and calcium. Not amenable by X-ray powder diffraction methods, the positions of such light cations in fully ion-exchanged versions of synthetic chabazite were determined through neutron powder diffraction methods. The study of more complex binary cation systems were conducted. Powder diffraction and solid state NMR methods (MAS, MQMAS) were used to examine cation site preferences and dislocations in these mixed-akali chabazites

  20. Cycloaliphatic epoxide resins for cationic UV - cure

    International Nuclear Information System (INIS)

    This paper introduces the cyclo - aliphatic epoxide resins used for the various applications of radiation curing and their comparison with acrylate chemistry. Radiation curable coatings and inks are pre - dominantly based on acrylate chemistry but over the last few years, cationic chemistry has emerged successfully with the unique properties inherent with cyclo - aliphatic epoxide ring structures. Wide variety of cationic resins and diluents, the formulation techniques to achieve the desired properties greatly contributes to the advancement of UV - curing technology

  1. Cations and activated sludge floc structure

    OpenAIRE

    Park, Chul

    2002-01-01

    This research was designed to investigate the effect of cations on activated sludge characteristics and also to determine their influence on digestion performance. For this purpose, cations in solution and in floc were evaluated along with various activated sludge characteristics and the collected waste activated sludge underwent both anaerobic and aerobic digestion. It was found that large amounts of biopolymer (protein + polysaccharide) remained in the effluent of WWTP that received high in...

  2. Test procedure for cation exchange chromatography

    International Nuclear Information System (INIS)

    The purpose of this test plan is to demonstrate the synthesis of inorganic antimonate ion exchangers and compare their performance against the standard organic cation exchangers. Of particular interest is the degradation rate of both inorganic and organic cation exchangers. This degradation rate will be tracked by determining the ion exchange capacity and thermal stability as a function of time, radiation dose, and chemical reaction

  3. Silica-based cationic bilayers as immunoadjuvants

    OpenAIRE

    Carmona-Ribeiro Ana M; da Costa Maria; Faquim-Mauro Eliana; Santana Mariana RA; Lincopan Nilton

    2009-01-01

    Abstract Background Silica particles cationized by dioctadecyldimethylammonium bromide (DODAB) bilayer were previously described. This work shows the efficiency of these particulates for antigen adsorption and presentation to the immune system and proves the concept that silica-based cationic bilayers exhibit better performance than alum regarding colloid stability and cellular immune responses for vaccine design. Results Firstly, the silica/DODAB assembly was characterized at 1 mM NaCl, pH 6...

  4. Anti-plasmodial action of de novo-designed, cationic, lysine-branched, amphipathic, helical peptides

    Directory of Open Access Journals (Sweden)

    Kaushik Naveen K

    2012-08-01

    Full Text Available Abstract Background A lack of vaccine and rampant drug resistance demands new anti-malarials. Methods In vitro blood stage anti-plasmodial properties of several de novo-designed, chemically synthesized, cationic, amphipathic, helical, antibiotic peptides were examined against Plasmodium falciparum using SYBR Green assay. Mechanistic details of anti-plasmodial action were examined by optical/fluorescence microscopy and FACS analysis. Results Unlike the monomeric decapeptides {(Ac-GXRKXHKXWA-NH2 (X = F,ΔF (Fm, ΔFm IC50 >100 μM}, the lysine-branched,dimeric versions showed far greater potency {IC50 (μM Fd 1.5 , ΔFd 1.39}. The more helical and proteolytically stable ΔFd was studied for mechanistic details. ΔFq, a K-K2 dendrimer of ΔFm and (ΔFm2 a linear dimer of ΔFm showed IC50 (μM of 0.25 and 2.4 respectively. The healthy/infected red cell selectivity indices were >35 (ΔFd, >20 (ΔFm2 and 10 (ΔFq. FITC-ΔFd showed rapid and selective accumulation in parasitized red cells. Overlaying DAPI and FITC florescence suggested that ΔFd binds DNA. Trophozoites and schizonts incubated with ΔFd (2.5 μM egressed anomalously and Band-3 immunostaining revealed them not to be associated with RBC membrane. Prematurely egressed merozoites from peptide-treated cultures were found to be invasion incompetent. Conclusion Good selectivity (>35, good resistance index (1.1 and low cytotoxicity indicate the promise of ΔFd against malaria.

  5. Polystyrene-divinylbenzene-glycidyl methacrylate stationary phase grafted with poly (amidoamine) dendrimers for ion chromatography.

    Science.gov (United States)

    Guo, Dandan; Lou, Chaoyan; Zhang, Peimin; Zhang, Jiajie; Wang, Nani; Wu, Shuchao; Zhu, Yan

    2016-07-22

    In this work, a novel ion exchange stationary phase based on different generations of poly (amidoamine) dendrimers (PAMAM) was developed for the determination of inorganic anions and carbohydrates. Synthesis of the PAMAM was carried out with the polymerization reaction of ethylenediamine and methyl acrylate. The synthesized PAMAM was then grafted to the polystyrene-divinylbenzene-glycidyl methacrylate (PS-GMA) to form PAMAM-based beads. These beads were finally modified with 1,4-butanediol diglycidyl ether (BDDE) to generate the anion exchanger, which were characterized by scanning electron microscopy (SEM), brunauer-emmett-teller (BET), fourier transform infrared spectroscopy (FTIR), and elemental analysis. Elemental analysis, breakthrough curves and capacity factors showed that more epoxy groups and higher PAMAM generations in stationary phase could result in higher anion exchange capacity. The efficiency, durability and stability of the proposed anion exchanger were investigated by using six inorganic anions (fluoride, chloride, nitrite, bromide, nitrate and sulfate) and four carbohydrates (trehalose, glucose, maltotriose and galacturonic acid) as analytes, respectively. The reliability of the proposed ion chromatographic stationary phase was demonstrated by determining the content of galacturonic acid in polysaccharides from Poria cocos and Atractylodes macrocephala. The relative standard deviations of retention time, peak height, and peak area for galacturonic acid were 0.39%, 1.22%, and 2.02%, respectively. The spiked recoveries were in the range of 88.29%-100.51% for plant polysaccharides. Due to the good structural homogeneity, intense internal porosity, biological compatibility and high density of active groups in PAMAM, this grafted stationary phase showed good ion-exchange characteristics, especially in biological charged molecules.

  6. Effect of mass transfer on the oxygen reduction reaction catalyzed by platinum dendrimer encapsulated nanoparticles.

    Science.gov (United States)

    Dumitrescu, Ioana; Crooks, Richard M

    2012-07-17

    Here we report on the effect of the mass transfer rate (k(t)) on the oxygen reduction reaction (ORR) catalyzed by Pt dendrimer-encapsulated nanoparticles (DENs) comprised of 147 and 55 atoms (Pt(147) and Pt(55)). The experiments were carried out using a dual-electrode microelectrochemical device, which enables the study of the ORR under high k(t) conditions with simultaneous detection of H(2)O(2). At low k(t) (0.02 to 0.12 cm s(-1)) the effective number of electrons involved in ORR, n(eff), is 3.7 for Pt(147) and 3.4 for Pt(55). As k(t) is increased, the mass-transfer-limited current for the ORR becomes significantly lower than the value predicted by the Levich equation for a 4-electron process regardless of catalyst size. However, the percentage of H(2)O(2) detected remains constant, such that n(eff) barely changes over the entire k(t) range explored (0.02 cm s(-1)). This suggests that mass transfer does not affect n(eff), which has implications for the mechanism of the ORR on Pt nanoparticles. Interestingly, there is a significant difference in n(eff) for the two sizes of Pt DENs (n(eff) = 3.7 and 3.5 for Pt(147) and Pt(55), respectively) that cannot be assigned to mass transfer effects and that we therefore attribute to a particle size effect.

  7. Polystyrene-divinylbenzene-glycidyl methacrylate stationary phase grafted with poly (amidoamine) dendrimers for ion chromatography.

    Science.gov (United States)

    Guo, Dandan; Lou, Chaoyan; Zhang, Peimin; Zhang, Jiajie; Wang, Nani; Wu, Shuchao; Zhu, Yan

    2016-07-22

    In this work, a novel ion exchange stationary phase based on different generations of poly (amidoamine) dendrimers (PAMAM) was developed for the determination of inorganic anions and carbohydrates. Synthesis of the PAMAM was carried out with the polymerization reaction of ethylenediamine and methyl acrylate. The synthesized PAMAM was then grafted to the polystyrene-divinylbenzene-glycidyl methacrylate (PS-GMA) to form PAMAM-based beads. These beads were finally modified with 1,4-butanediol diglycidyl ether (BDDE) to generate the anion exchanger, which were characterized by scanning electron microscopy (SEM), brunauer-emmett-teller (BET), fourier transform infrared spectroscopy (FTIR), and elemental analysis. Elemental analysis, breakthrough curves and capacity factors showed that more epoxy groups and higher PAMAM generations in stationary phase could result in higher anion exchange capacity. The efficiency, durability and stability of the proposed anion exchanger were investigated by using six inorganic anions (fluoride, chloride, nitrite, bromide, nitrate and sulfate) and four carbohydrates (trehalose, glucose, maltotriose and galacturonic acid) as analytes, respectively. The reliability of the proposed ion chromatographic stationary phase was demonstrated by determining the content of galacturonic acid in polysaccharides from Poria cocos and Atractylodes macrocephala. The relative standard deviations of retention time, peak height, and peak area for galacturonic acid were 0.39%, 1.22%, and 2.02%, respectively. The spiked recoveries were in the range of 88.29%-100.51% for plant polysaccharides. Due to the good structural homogeneity, intense internal porosity, biological compatibility and high density of active groups in PAMAM, this grafted stationary phase showed good ion-exchange characteristics, especially in biological charged molecules. PMID:27311659

  8. Self-assembly, DNA complexation, and pH response of amphiphilic dendrimers for gene transfection

    NARCIS (Netherlands)

    Guillot-Nieckowski, Marine; Joester, Derk; Stöhr, Meike; Losson, Myriam; Adrian, Marc; Wagner, Bjoern; Kansy, Manfred; Heinzelmann, Harry; Pugin, Raphael; Diederich, Francois; Gallani, Jean-Louis

    2007-01-01

    Cationic lipids and polymers are routinely used for cell transfection, and a variety of structure-activity relation data have been collected. Few studies, however, focus on the structural aspects of self-assembly as a crucial control parameter for gene delivery. We present here the observations coll

  9. Kilogram-scale synthesis of a second-generation dendrimer based on 1,3,5-triazine using green and industrially compatible methods with a single chromatographic step.

    Science.gov (United States)

    Chouai, Abdellatif; Simanek, Eric E

    2008-03-21

    A kilogram scale, divergent and iterative synthesis of a second generation, triazine dendrimer with 12 protected amines on the periphery using common laboratory equipment is reported. The route benefits from common reaction conditions, inexpensive reagents, and aqueous solvents. From the monomers, the desired product dendrimer--the last uncommitted intermediate that leads to a range of committed, generation three targets--can be obtained in 70% overall yield. Of critical importance in the execution of this divergent synthesis is the differential reactivity of chlorine atoms of trichlorotriazine. The stepwise, nucleophilic aromatic substitution of these atoms with amine nucleophiles is both the basis for the dendrimer growth as well as incorporation of solubilizing piperidine groups. Intermediates are obtained and purified through precipitation and/or extraction protocols with the exception of the final product. Isolation of the target dendrimer requires a single silica gel plug filtration. The purity of this material is assessed at >93%, a level consistent with and/or exceeding other commercially available targets.

  10. Sulfur dioxide gas detection by reversible _1-SO2-Pt bond formation as a novel application for functionalised metallo-dendrimers

    NARCIS (Netherlands)

    Koten, G. van; Albrecht, M.A.; Gossage, R.A.; Spek, A.L.

    1998-01-01

    Multimetallics such as dendrimer 3 which are functionalised at their periphery with platinum(II) metal centres reversibly absorb SO2 to yield macromolecules with significantly enhanced solubility characteristics and drastic colour changes; properties which make these compounds highly active sensors

  11. 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

    in association constants are higher when the urea function is added to the guests for the host with the longer spacer, indicating a better fit. Collision-induced dissociation mass spectrometry (CID-MS) is used to study the stability of the six motifs using the corresponding third generation dendrimer. A similar...

  12. Ultrasensitive Lipopolysaccharides Detection Based on Doxorubicin Conjugated N-(Aminobutyl)-N-(ethylisoluminol) as Electrochemiluminescence Indicator and Self-Assembled Tetrahedron DNA Dendrimers as Nanocarriers.

    Science.gov (United States)

    Xie, Shunbi; Dong, Yongwang; Yuan, Yali; Chai, Yaqin; Yuan, Ruo

    2016-05-17

    The preparation of self-assembled DNA nanostructure with different sizes and shapes has been one of the most promising research areas in recent years, while the application of these DNA nanostructures in biosensors is far from fully developed. Here, we presented a novel carrier system to construct an electrochemiluminescence (ECL) aptasensor for ultrasensitive determination of lipopolysaccharides (LPS) on the basis of self-assembled tetrahedron DNA dendrimers. Doxorubicin (Dox), a well-known intercalator of double stranded DNA (dsDNA), was conjugated with the ECL luminophore of N-(aminobutyl)-N-(ethylisoluminol) (ABEI) to form a new type of ECL indicators (Dox-ABEI), which could noncovalently attach to dsDNA through intercalation. Based on this property, self-assembled tetrahedron DNA dendrimers were employed as an efficient nanocarrier to achieve a high loading efficiency for Dox-ABEI with significantly amplified ECL signal output. Streptavidin (SA) and biotin, a typical ligand-receptor pair, has been chosen to anchor the tetrahedron DNA dendrimers on the electrode surface. Moreover, by converting LPS content into DNA output, catalyzed hairpin assembly (CHA) target recycling signal amplification strategy was also adopted to enhance the sensitivity of the ECL aptasensor. With combining the loading power of the tetrahedron DNA dendrimers for ECL indicators, the inherent high sensitivity of ECL technique and target recycling for signal amplification, the proposed strategy showed a detection limit of 0.18 fg/mL for LPS.

  13. Detection of dopamine in non-treated urine samples using glassy carbon electrodes modified with PAMAM dendrimer-Pt composites

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, M.G. [Laboratory of Bioelectrochemistry, Centro de Investigacion y Desarrollo Tecnologico en Electroquimica, S. C., Parque Tecnologico, Queretaro, Sanfandila, Pedro Escobedo 76703, Queretaro (Mexico); Department of Chemistry, Universidad de Guanajuato, Cerro de la Venada S/N Col. Pueblito de Rocha, 36040 Guanajuato, Gto (Mexico); Armendariz, G.M.E.; Godinez, Luis A.; Torres, J. [Laboratory of Bioelectrochemistry, Centro de Investigacion y Desarrollo Tecnologico en Electroquimica, S. C., Parque Tecnologico, Queretaro, Sanfandila, Pedro Escobedo 76703, Queretaro (Mexico); Sepulveda-Guzman, S. [Centro de Innovacion, Investigacion y Desarrollo en Ingenieria y Tecnologia, Facultad de Ingenieria Mecanica y Electrica, Universidad Autonoma de Nuevo Leon, Av. Universidad, San Nicolas de los Garza, Nuevo Leon, 66451 Nuevo Leon (Mexico); Bustos, E., E-mail: ebustos@cideteq.mx [Laboratory of Bioelectrochemistry, Centro de Investigacion y Desarrollo Tecnologico en Electroquimica, S. C., Parque Tecnologico, Queretaro, Sanfandila, Pedro Escobedo 76703, Queretaro (Mexico)

    2011-09-01

    Composites of hydroxyl-terminated PAMAM dendrimers, generation 4.0 (64 peripheral OH groups) containing Pt nanoparticles were synthesized at different reaction times using a microwave reactor. The synthetic procedure resulted in dendrimer encapsulated nanoparticles of Pt (DENs-Pt) of 1.53 {+-} 0.17 nm diameter that was calculated from transmission electron microscopy, and the Pt nanoparticles had single crystal plane in (1 1 1) orientation determinate by selective area diffraction. Each composite was electrochemically immobilized on a pre-functionalized glassy carbon (GC) electrode that was incorporated as a flow injection amperometric (FIA) detector, for the selective detection and quantification of dopamine (DA) in untreated urine samples. Comparison of the analytical performance of the novel electrochemical detector revealed that the DENs-Pt modified GC electrode with the composite synthesized for 30 min in the microwave reactor, showed the best response for the detection of DA in samples of non-treated urine, being the detection and quantification limits smaller (19 and 9 ppb, respectively) than those corresponding to the naked a GC electrode (846 and 423 ppb, respectively) using the FIA detector. In addition, it was found that this electroanalytical approach suffers minimal matrix effects that arise in the analysis of DA in untreated samples of urine.

  14. Synthesis of nanomagnetic fluids and their UV spectrophotometric response with aliphatic organic acids and 1st tier dendrimers

    Science.gov (United States)

    Pandya, Shivani R.; Singh, Man

    2016-04-01

    Synthesis of Magnetic nanoparticles were made using coprecipitation method on mixing Fe+3 and Fe+2 in 2:1 ratio with aqueous 8M NaOH which on heating at 90°C for 2 h has yielded 85% magnetic (Fe3O4) nanoparticles (MNPs), characterized by XRD, VSM, SEM, and HR-TEM. The formic acid (FA), oxalic acid (OA) and citric acid (CA), the series of aliphatic organic acids along with Trimesoyl 1, 3, 5 tridimethyl malonate (TTDMM), trimesoyl 1, 3, 5 tridiethyl malonate (TTDEM), trimesoyl 1, 3, 5 tridipropyl malonate (TTDPM), trimesoyl 1, 3, 5 tridibutyl malonate (TTDBM) and trimesoyl 1, 3, 5 tridihexyl malonate (TTDHM) 1st tier dendrimers were used separately for preparing nanomagnetic fluid. From 25 to 150 µM MNPs at an interval of 25 µM were dispersed in 150 µM of acids and dendrimers separately with DMSO. UV-VIS spectrophotometry showed a maximum MNPs dispersion with TTDMM against others and found to be most stable nanomagnetic fluid on account of capping type mechanism of acids.

  15. Detection of Lymph Node Involvement in Hematologic Malignancies Using Micromagnetic Resonance Lymphangiography with a Gadolinum-Labeled Dendrimer Nanoparticle

    Directory of Open Access Journals (Sweden)

    Hisataka Kobayashi

    2005-11-01

    Full Text Available Animal models of lymphoma should reflect their counterparts in humans; however, it can be difficult to ascertain whether an induced disease is intralymphatic or extralymphatic based on direct visualization. Current imaging methods are insufficient for identifying lymphatic and intralymphatic involvement. To differentiate intralymphatic from extralymphatic involvement, we have developed a magnetic resonance imaging-based lymphangiography method and tested it on two animal models of lymphoma. A gadolinium (Gd-labeled dendrimer nanoparticle (generation-6; ~220 kDa/f10 nm was injected interstitially into mice bearing hematologic malignancies to perform dynamic micromagnetic resonance lymphangiography (micro-MRL. Both a standard T1-weighted 3D fast spoiled gradient echo and a T2/T1-weighted 3D fast imaging employing steady-state acquisition (3D-FIESTA-C were compared in an imaging study to differentiate intralymphatic from extralymphatic involvement of tumors. The lymphatics and lymph nodes were visualized with both methods in all cases. In addition, 3D-FIESTA-C depicted both the lymphatic system and the extralymphatic tumor. In an animal model, 3D-FIESTA-C demonstrated that the bulk of the tumor thought to be intralymphatic was actually extralymphatic. In conclusion, micro-MRL, using Gd-labeled dendrimer nanoparticles with the combined method, can define both the normal and abnormal lymphatics and can distinguish intralymphatic from extralymphatic diseases in mouse models of malignant lymphoma.

  16. Embryonic Stem Cells Maintain an Undifferentiated State on Dendrimer-Immobilized Surface with d-Glucose Display

    Directory of Open Access Journals (Sweden)

    Masahito Taya

    2011-12-01

    Full Text Available In serial passaging cultures of mouse embryonic stem (ES cells, we employed a dendrimer-immobilized substrate that displayed d-glucose as a terminal ligand. The d-glucose-displaying dendrimer (GLU/D surface caused the ES cells to form loosely attached spherical colonies, while those on a gelatin-coated surface formed flatter colonies that were firmly attached to the surface. Despite the morphological similarities between the colonies on the GLU/D surface and aggregates on a conventional bacteriological dish, immunostaining and RT-PCR analyses revealed the maintenance of cells within the spherical colonies on the GLU/D surface in an undifferentiated state with very low expressions of primitive endoderm markers. On the bacteriological dish, however, the cells within the aggregates showed a different cellular state with partial differentiation into the primitive endoderm lineage, and the expression level increased gradually along with the number of passages. These results indicate that the GLU/D surface can be a potential tool for controlling the ES cell morphology and then govern their self-renewal and fate.

  17. Inclusion of thiol DAB dendrimer/CdSe quantum dots based in a membrane structure: Surface and bulk membrane modification

    International Nuclear Information System (INIS)

    Highlights: ► Fluorescent nanocomposite based in CdSe quantum dots (QDs) coated by thiol polypropylenimine (DAB). ► Bulk chemical characterization by TEM and EDAX ► Inclusion of the S-DAB-CdSe QDs in a cellulosic support and its characterization by Fluorescence and XPS. ► Electrical characterization by Impedance Spectroscopy of dry and wet samples containing a heavy metal. -- Abstract: The behavior of a fluorescent nanocomposite, obtained by means of a thiol polypropylenimine dendrimer of third generation coated with CdSe quantum dots, and embedded in a hydrophilic cellulosic membrane as support is electrochemically studied in order to evaluate its applicability as a sensor in liquid media. The characterization of the nanocomposite by TEM and EDAX shows uniform nano morphology (size comprised in the range 60–90 nm) and composition, respectively. The analysis of the engineered hybrid cellulose-dendrimer quantum dots material by confocal fluorescence microscopy indicates almost mono-dispersion distribution of the nanocomposite when irradiated under UV light, while its presence on the film surface was determined by X-ray photoelectron spectroscopy. Impedance spectroscopy measurements performed with dry membrane samples show a decrease in the conductivity and dielectric constant of the modified membrane in comparison with the raw support. Electrical changes in the modified film associated to the presence of Cd(II) uptakes from a Cl2Cd solution were also obtained. These results support the possible application of this nanocomposite material as heavy metal sensor in liquid media

  18. Modification of poly(L-lactic acid) electrospun fibers and films with poly(propylene imine) dendrimer

    Science.gov (United States)

    Khaliliazar, Sh.; Akbari, S.; Kish, M. H.

    2016-02-01

    Poly(L-lactic acid) (PLLA) electrospun fibers and films were modified with the second generation of poly(propylene imine) dendrimer (PPI-G2) by three different approaches, namely, sodium hydroxide hydrolysis, plasma treatment and direct application of PPI-G2. For the first and the second approaches, PLLA was modified by sodium hydroxide hydrolysis or plasma treatment to produce carboxylic acid groups. Then, the carboxylic acid groups were activated by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC) and N,N‧-dicyclohexyl carbodiimide (DCC) as a hetero bi-functional cross-linker. The cross-linkers promoted the grafting of carboxylic acid groups on the modified PLLA with NH2 groups of PPI-G2. In the third approach, the PPI-G2 dendrimer was directly used as an aminolysis agent for the functionalization of PLLA in a one step process. FTIR analysis confirmed the presence of sbnd NH2 groups of PPI-G2 on the modified PLLA samples, resulting from each one of the three modification methods. Studies by SEM shows bead free electrospun fibers. Also, FE-SEM shows nano-cracks on the surface of films after modification. Contact angle, drug release tests, antibacterial effects and the dying results confirmed that these functionalization methods increased hydrophilicity and reactive side-chains of PLLA in the wet chemical process resulted in providing host-guest properties on the PLLA surface for adsorbing various kinds of guest molecules.

  19. Structural characterization and catalytic activity of Pt dendrimer encapsulated nanoparticles supported over Al2O3 for SCR of NOx.

    Science.gov (United States)

    Bae, HyunSook; Rao, Komateedi N; Ha, HeonPhil

    2011-07-01

    Pt/Al2O3 and Pt-Mg/Al2O3 nano composites were successfully prepared by dendrimer templated synthesis route. The obtained dendritic nanoparticles were dispersed in alumina support and they were evaluated for SCR of NOx using methane as reductant. Thermal analysis results of uncalcined samples revealed that the oxygen can accelerate the rate of dendrimer shell decomposition. X-ray diffractograms of 500 degrees C calcined samples disclosed the amorphous nature of materials, whereas 1000 degrees C air calcined samples showed enhanced crystallinity as well as diffraction pattern corresponding to Pt and PtO. HRTEM images of Pt40-G4OH dendritic nanoparticles showed uniform particulate distribution with average particle size of 2.4 nm. The STEM results of 0.5 Pt/Al2O3 sample calcined at 500 degrees C exhibited a wide range of particles between 2 and 20 nm. This indicates the huge segregation of platinum metal particles during impregnation and subsequent calcination. Among the synthesized materials 0.5 wt% Pt/Al2O3 sample showed excellent conversion and selectivity for SCR of NOx.

  20. Innate cation sensitivity in a semiconducting polymer.

    Science.gov (United States)

    Althagafi, Talal M; Algarni, Saud A; Grell, Martin

    2016-09-01

    Water-gated organic thin film transistors (OTFTs) using the hole transporting semiconducting polymer, poly(2,5-bis(3-hexadecylthiophen-2-yl)thieno[3,2-b]thiophene) (PBTTT), show an innate response of their threshold voltage to the addition of divalent metal cations to the gating water, without deliberately introducing an ion-sensitive component. A similar threshold response is shown for several divalent cations, but is absent for monovalent cations. Response is absent for transistors using the inorganic semiconductor ZnO, or the similar organic semiconductor poly(3-hexylthiophene) (rrP3HT), instead of PBTTT. We assign innate cation sensitivity to residues of the organometallic Pd(0) complex used as catalyst in PBTTT synthesis which bears strong resemblance to typical metal chelating agents. Organometallic Pd(0) residues are absent from ZnO, and also from rrP3HT which is polymerised with a different type of catalyst. However, when Pd(0) complex is deliberately added to rrP3HT casting solutions, resulting OTFTs also display threshold response to a divalent cation. PMID:27343580

  1. Forging Colloidal Nanostructures via Cation Exchange Reactions

    Science.gov (United States)

    2016-01-01

    Among the various postsynthesis treatments of colloidal nanocrystals that have been developed to date, transformations by cation exchange have recently emerged as an extremely versatile tool that has given access to a wide variety of materials and nanostructures. One notable example in this direction is represented by partial cation exchange, by which preformed nanocrystals can be either transformed to alloy nanocrystals or to various types of nanoheterostructures possessing core/shell, segmented, or striped architectures. In this review, we provide an up to date overview of the complex colloidal nanostructures that could be prepared so far by cation exchange. At the same time, the review gives an account of the fundamental thermodynamic and kinetic parameters governing these types of reactions, as they are currently understood, and outlines the main open issues and possible future developments in the field. PMID:26891471

  2. Cationically polymerizable monomers derived from renewable sources

    Energy Technology Data Exchange (ETDEWEB)

    Crivello, J.V.

    1992-10-01

    The objectives of this project are to design and synthesize novel monomers which orginate from renewable biological sources and to carry out their rapid, efficient, pollution-free and energy efficient cationic polymerization to useful products under the influence of ultraviolet light or heat. A summary of the results of the past year's research on cationically polymerizable monomers derived from renewable sources is presented. Three major areas of investigation corresponding to the different classes of naturally occurring starting materials were investigated; epoxidized terpenes and natural rubber and vinyl ethers from alcohols and carbohydrates.

  3. Mixed cation effect in sodium aluminosilicate glasses

    DEFF Research Database (Denmark)

    Kjeldsen, Jonas; Smedskjær, Morten Mattrup; Mauro, John C.;

    , network structure, and the resistances associated with the deformation processes in mixed cation glasses by partially substituting magnesium for calcium and calcium for lithium in sodium aluminosilicate glasses. We use Raman and 27Al NMR spectroscopies to obtain insights into the structural...... and topological features of these glasses and we use AFM to quantify the resistances associated with each deformation process under Vickers indentation. We demonstrate that the mixed cation effect manifests itself as a maximum in the amount of bonded tetrahedral units and as a minimum in liquid fragility index...

  4. Cation Effect on Copper Chemical Mechanical Polishing

    Institute of Scientific and Technical Information of China (English)

    WANG Liang-Yong; LIU Bo; SONG Zhi-Tang; FENG Song-Lin

    2009-01-01

    We examine the effect of cations in solutions containing benzotriazole (BTA) and H2O2 on copper chemical mechanical polishing (CMP). On the base of atomic force microscopy (AFM) and material removal rate (MRR) results, it is found that ammonia shows the highest MRR as well as good surface after CMP, while KOH demon-strates the worst performance. These results reveal a mechanism that sma//molecules with lone-pairs rather than molecules with steric effect and common inorganic cations are better for copper CMP process, which is indirectly confirmed by open circuit potential (OCP).

  5. Cation Selectivity in Biological Cation Channels Using Experimental Structural Information and Statistical Mechanical Simulation.

    Directory of Open Access Journals (Sweden)

    Justin John Finnerty

    Full Text Available Cation selective channels constitute the gate for ion currents through the cell membrane. Here we present an improved statistical mechanical model based on atomistic structural information, cation hydration state and without tuned parameters that reproduces the selectivity of biological Na+ and Ca2+ ion channels. The importance of the inclusion of step-wise cation hydration in these results confirms the essential role partial dehydration plays in the bacterial Na+ channels. The model, proven reliable against experimental data, could be straightforwardly used for designing Na+ and Ca2+ selective nanopores.

  6. Water adsorption on free cobalt cluster cations

    NARCIS (Netherlands)

    D.M. Kiawi; J.M. Bakker; J. Oomens; W.J. Buma; Z. Jamshidi; L. Visscher; L.B.F.M. Waters

    2015-01-01

    Cationic cobalt clusters complexed with water Con+-​H2O (n = 6-​20) are produced through laser ablation and investigated via IR multiple photon dissocn. (IR-​MPD) spectroscopy in the 200-​1700 cm-​1 spectral range. All spectra exhibit a resonance close to the 1595 cm-​1 frequency of the free water b

  7. Simultaneous anion and cation mobility in polypyrrole

    DEFF Research Database (Denmark)

    Skaarup, Steen; Bay, Lasse; Vidanapathirana, K.;

    2003-01-01

    Polypyrrole (PPy) polymer films permanently doped with large, immobile anion dodecyl benzene sulfonate (DBS) have been characterized by cyclic voltammetry in order to clarify the roles of cations and anions in the aqueous electrolyte as mobile ions in the film. Aqueous solutions of 0.05-0.1 M alk...

  8. Resonance raman studies of phenylcyclopropane radical cations

    NARCIS (Netherlands)

    Godbout, J.T.; Zuilhof, H.; Heim, G.; Gould, I.R.; Goodman, J.L.; Dinnocenzo, J.P.; Myers Kelley, A.

    2000-01-01

    Resonance Raman spectra of the radical cations of phenylcyclopropane and trans-1-phenyl-2-methylcyclopropane are reported. A near-UV pump pulse excites a photosensitizer which oxidizes the species of interest, and a visible probe pulse delayed by 35 ns obtains the spectrum of the radical ion. The tr

  9. Anionic/cationic complexes in hair care.

    Science.gov (United States)

    O'Lenick, Tony

    2011-01-01

    The formulation of cosmetic products is always more complicated than studying the individual components in aqueous solution. This is because there are numerous interactions between the components, which make the formulation truly more than the sum of the parts. This article will look at interactions between anionic and cationic surfactants and offer insights into how to use these interactions advantageously in making formulations.

  10. Cationic lipids and cationic ligands induce DNA helix denaturation: detection of single stranded regions by KMnO4 probing.

    Science.gov (United States)

    Prasad, T K; Gopal, Vijaya; Rao, N Madhusudhana

    2003-09-25

    Cationic lipids and cationic polymers are widely used in gene delivery. Using 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) as a cationic lipid, we have investigated the stability of the DNA in DOTAP:DNA complexes by probing with potassium permanganate (KMnO4). Interestingly, thymidines followed by a purine showed higher susceptibility to cationic ligand-mediated melting. Similar studies performed with other water-soluble cationic ligands such as polylysine, protamine sulfate and polyethyleneimine also demonstrated melting of the DNA but with variations. Small cations such as spermine and spermidine and a cationic detergent, cetyl trimethylammonium bromide, also rendered the DNA susceptible to modification by KMnO4. The data presented here provide direct proof for melting of DNA upon interaction with cationic lipids. Structural changes subsequent to binding of cationic lipids/ligands to DNA may lead to instability and formation of DNA bubbles in double-stranded DNA.

  11. Dendrimer teknolojisi kullanılarak aromaterapi özelliğine sahip pamuklu fonksiyonel kumaş eldesi

    OpenAIRE

    Barış, Berkay; Atav, Rıza

    2012-01-01

    Günümüzde tekstil terbiyesinde önem kazanmaya başlamış olan kavramlardan biri nano-teknolojidir. Tekstil terbiyesinde nano-teknolojik ürünler kullanılarak konvansiyonel yöntemlere kıyasla birçok avantajlar sağlanabilmektedir. Bu anlamda henüz tekstil terbiyesinde kullanımı oldukça yeni olan bir nano-teknolojik ürün de dendrimerdir. Bu çalışmada dendrimer teknolojisi kullanılarak pamuklu kumaşlara aromaterapi fonksiyonelliği kazandırılması amaçlanmıştır. Yapılan çalışmalar sonucunda dendrimerl...

  12. Amperometric biosensor based on carbon nanotubes coated with polyaniline/dendrimer-encapsulated Pt nanoparticles for glucose detection

    Energy Technology Data Exchange (ETDEWEB)

    Xu Lihuan [Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Zhu Yihua, E-mail: yhzhu@ecust.edu.cn [Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Yang Xiaoling; Li Chunzhong [Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China)

    2009-05-05

    A novel amperometric glucose biosensor based on the nanocomposites of multi-wall carbon nanotubes (CNT) coated with polyaniline (PANI) and dendrimer-encapsulated Pt nanoparticles (Pt-DENs) is prepared. CNT coated with protonated PANI is in situ synthesized and Pt-DENs is absorbed on PANI/CNT composite surface by self-assembly method. Then Glucose oxidase (GOx) is crosslink-immobilizated onto Pt-DENs/PANI/CNT composite film. The results show that the fabricated GOx/Pt-DENs/PANI/CNT electrode exhibits excellent response performance to glucose, such as low detection limit (0.5 {mu}M), wide linear range (1 {mu}M-12 mM), short response time (about 5 s), high sensitivity (42.0 {mu}A mM{sup -1} cm{sup -2}) and stability (83% remains after 3 weeks).

  13. Cation-cation interactions, magnetic communication and reactivity of the pentavalent uraniumion [U(NR)2]+

    Energy Technology Data Exchange (ETDEWEB)

    Spencer, Liam P [Los Alamos National Laboratory; Schelter, Eric J [Los Alamos National Laboratory; Boncella, James M [Los Alamos National Laboratory; Yang, Ping [Los Alamos National Laboratory; Gsula, Robyn L [NON LANL; Scott, Brian L [Los Alamos National Laboratory; Thompson, Joe D [Los Alamos National Laboratory; Kiplinger, Jacqueline L [Los Alamos National Laboratory; Batista, Enrique R [Los Alamos National Laboratory

    2009-01-01

    The dimeric bis(imido) uranium complex [{l_brace}U(NtBu)2(I)(tBu2bpy){r_brace}2] (see picture; U green, N blue, I red) has cation-cation interactions between [U(NR)2]+ ions. This f1-f1 system also displays f orbital communication between uranium(V) centers at low temperatures, and can be oxidized to generate uranium(VI) bis(imido) complexes.

  14. Target-catalyzed autonomous assembly of dendrimer-like DNA nanostructures for enzyme-free and signal amplified colorimetric nucleic acids detection.

    Science.gov (United States)

    He, Hongfei; Dai, Jianyuan; Duan, Zhijuan; Meng, Yan; Zhou, Cuisong; Long, Yuyin; Zheng, Baozhan; Du, Juan; Guo, Yong; Xiao, Dan

    2016-12-15

    Self-assembly of DNA nanostructures is of great importance in nanomedicine, nanotechnology and biosensing. Herein, a novel target-catalyzed autonomous assembly pathway for the formation of dendrimer-like DNA nanostructures that only employing target DNA and three hairpin DNA probes was proposed. We use the sticky-ended Y shape DNA (Y-DNA) as the assembly monomer and it was synthesized by the catalyzed hairpin assembly (CHA) instead of the DNA strand annealing method. The formed Y-DNA was equipped with three ssDNA sticky ends and two of them were predesigned to be complementary to the third one, then the dendrimer-like DNA nanostructures can be obtained via an autonomous assembly among these sticky-ended Y-DNAs. The resulting nanostructure has been successfully applied to develop an enzyme-free and signal amplified gold nanoparticle (AuNP)-based colorimetric nucleic acids assay. PMID:27498325

  15. Avoiding Steric Congestion in Dendrimer Growth through Proportionate Branching. A Twist on da Vinci's Rule of Tree Branching

    Energy Technology Data Exchange (ETDEWEB)

    Yue, Xuyi [Univ. of Maryland, Baltimore, MD (United States); Taraban, Marc B. [Univ. of Maryland, Baltimore, MD (United States); Hyland, Laura L. [Univ. of Maryland, Baltimore, MD (United States); Yu, Yihua Bruce [Univ. of Maryland, Baltimore, MD (United States)

    2012-10-05

    In making defect-free macromolecules, the challenge occurs during chemical synthesis. This challenge is especially pronounced in dendrimer synthesis where exponential growth quickly leads to steric congestion. To overcome this difficulty, proportionate branching in dendrimer growth is proposed. In proportionate branching, both the number and the length of branches increase exponentially but in opposite directions to mimic tree growth. The effectiveness of this strategy is demonstrated through the synthesis of a fluorocarbon dendron containing 243 chemically identical fluorine atoms with a MW of 9082 Da. Monodispersity is confirmed by nuclear magnetic resonance spectroscopy, mass spectrometry, and small-angle X-ray scattering. Moreover, growing different parts proportionately, as nature does, could be a general strategy to achieve defect-free synthesis of macromolecules.

  16. Structurally Distinct Cation Channelrhodopsins from Cryptophyte Algae.

    Science.gov (United States)

    Govorunova, Elena G; Sineshchekov, Oleg A; Spudich, John L

    2016-06-01

    Microbial rhodopsins are remarkable for the diversity of their functional mechanisms based on the same protein scaffold. A class of rhodopsins from cryptophyte algae show close sequence homology with haloarchaeal rhodopsin proton pumps rather than with previously known channelrhodopsins from chlorophyte (green) algae. In particular, both aspartate residues that occupy the positions of the chromophore Schiff base proton acceptor and donor, a hallmark of rhodopsin proton pumps, are conserved in these cryptophyte proteins. We expressed the corresponding polynucleotides in human embryonic kidney (HEK293) cells and studied electrogenic properties of the encoded proteins with whole-cell patch-clamp recording. Despite their lack of residues characteristic of the chlorophyte cation channels, these proteins are cation-conducting channelrhodopsins that carry out light-gated passive transport of Na(+) and H(+). These findings show that channel function in rhodopsins has evolved via multiple routes. PMID:27233115

  17. Radiation chemistry of aromatic dimer radical cations

    International Nuclear Information System (INIS)

    π-π Interactions of aromatic molecules are paid attention much in many fields, especially biology, chemistry, and applied physics, represented as protein, DNA, electron donor-accepter complexes, charge transfers, and self assembly molecules. Aromatic molecules including benzene rings are the simplest case to study the π-π interactions. To interpret the charge resonance (CR) structure in the dimer radical cations, spectroscopic and ESR methods have been carried out. The spectroscopic study on the dimer radical ion of molecules with two chromophores would be profitable to identify the electronic and configurational properties. In this article, dynamics of the dimer radical cation of benzenes, polystyrenes, and resist polymers is described on the basis of direct observation of CR band by the nanosecond pulse radiolysis and low temperature γ-radiolysis methods. (author)

  18. Titanocene Dichloride Complexes Bonded to Carbosilane Dendrimers Via a Spacer of Variable Length – Molecular Dynamics Calculations and Catalysis of Allylic Coupling Reactions

    OpenAIRE

    Strašák, T. (Tomáš); Jaroschik, F.; M. Malý; Čermák, J.; Sýkora, J.; Fajgar, R. (Radek); Karban, J.; Harakat, D.

    2014-01-01

    Carbosilane metallodendrimers of the first and second generation containing 4, 8 or 16 titanocene dichloride endgroups were prepared by the normal hydrosilylation method. Different chain lengths of the carbon spacer between the dendrimer and the Cp linkage were investigated. Computer atomistic models of the second generation metallodendrimers with the length of carbon spacer n = 1, 3 and 5 carbon atoms were created, parametrized, and consequently simulated in THF solvent using molecular dynam...

  19. Selective aggregation of PAMAM dendrimer nanocarriers and PAMAM/ZnPc nanodrugs on human atheromatous carotid tissues: a photodynamic therapy for atherosclerosis

    OpenAIRE

    Spyropoulos-Antonakakis, Nikolaos; Sarantopoulou, Evangelia; Trohopoulos, Panagiotis N; Stefi, Aikaterina L; Kollia, Zoe; Gavriil, Vassilios E; Bourkoula, Athanasia; Petrou, Panagiota S.; Kakabakos, Sotirios; Semashko, Vadim V; Nizamutdinov, Alexey S; Cefalas, Alkiviadis-Constantinos

    2015-01-01

    Photodynamic therapy (PDT) involves the action of photons on photosensitive molecules, where atomic oxygen or OH− molecular species are locally released on pathogenic human cells, which are mainly carcinogenic, thus causing cell necrosis. The efficacy of PDT depends on the local nanothermodynamic conditions near the cell/nanodrug system that control both the level of intracellular translocation of nanoparticles in the pathogenic cell and their agglomeration on the cell membrane. Dendrimers ar...

  20. Alkaline earth cation extraction from acid solution

    Science.gov (United States)

    Dietz, Mark; Horwitz, E. Philip

    2003-01-01

    An extractant medium for extracting alkaline earth cations from an aqueous acidic sample solution is described as are a method and apparatus for using the same. The separation medium is free of diluent, free-flowing and particulate, and comprises a Crown ether that is a 4,4'(5')[C.sub.4 -C.sub.8 -alkylcyclohexano]18-Crown-6 dispersed on an inert substrate material.

  1. Cation Permeability in Soybean Aleurone Layer

    OpenAIRE

    Noda, Hiroko; Fukuda, Mitsuru

    1998-01-01

    The permeation of water and ions into bean seeds is essential for processing and cooking of beans. The permeability of cations, K, Na, Ca, and Mg ions, into soybean seed tissue, especially aleurone layer, during water uptake was investigated to characterize the ion permeation into soybeans. Aleurone layers and seed coats contained relatively high concentration of endogenous K and Ca ions, and endogenous Ca ion, respectively. The amounts of Ca ion entered seed coats and aleurone layers were gr...

  2. Low cation coordination in oxide melts

    Energy Technology Data Exchange (ETDEWEB)

    Skinner, Lawrie [State University of New York, Stony Brook; Benmore, Chris J [Argonne National Laboratory (ANL); Du, Jincheng [University of North Texas; Weber, Richard [Argonne National Laboratory (ANL); Neuefeind, Joerg C [ORNL; Tumber, Sonia [Materials Development, Inc., Evanston, IL; Parise, John B [Stony Brook University (SUNY)

    2014-01-01

    The complete set of Faber-Ziman partial pair distribution functions for a rare earth oxide liquid were measured for the first time by combining aerodynamic levitation, neutron diffraction, high energy x-ray diffraction and isomorphic substitution using Y2 O3 and Ho2 O3 melts. The average Y- O coordination is measured to be 5.5(2), which is significantly less than the octahedral coordination of crystalline Y2 O3 (or Ho2 O3 ). Investigation of high temperature La2 O3 , ZrO2 , SiO2 , and Al2 O3 melts by x-ray diffraction and molecular dynamics simulations also show lower-than-crystal cation- oxygen coordination. These measurements suggest a general trend towards lower M-O coordination compared to their crystalline counterparts. It is found that this coordination number drop is larger for lower field strength, larger radius cations and is negligible for high field strength (network forming) cations. These findings have broad implications for predicting the local structure and related physical properties of metal-oxide melts and oxide glasses.

  3. Low Cation Coordination in Oxide Melts

    Science.gov (United States)

    Skinner, L. B.; Benmore, C. J.; Weber, J. K. R.; Du, J.; Neuefeind, J.; Tumber, S. K.; Parise, J. B.

    2014-04-01

    The complete set of partial pair distribution functions for a rare earth oxide liquid are measured by combining aerodynamic levitation, neutron and x-ray diffraction on Y2O3, and Ho2O3 melts at 2870 K. The average Y-O (or Ho-O) coordination of these isomorphic melts is measured to be 5.5(2), which is significantly less than the octahedral coordination of crystalline Y2O3 (or Ho2O3). Investigation of La2O3, ZrO2, and Al2O3 melts by x-ray diffraction and molecular dynamics simulations also show lower-than-crystal cation-oxygen coordination. These measurements suggest a general trend towards lower coordination compared to their crystalline counterparts. It is found that the coordination drop is larger for lower field strength, larger radius cations and is negligible for high field strength (network forming) cations, such as SiO2. These findings have broad implications for predicting the local structure and related physical properties of metal-oxide melts and oxide glasses.

  4. Limited data speaker identification

    Indian Academy of Sciences (India)

    H S Jayanna; S R Mahadeva Prasanna

    2010-10-01

    In this paper, the task of identifying the speaker using limited training and testing data is addressed. Speaker identification system is viewed as four stages namely, analysis, feature extraction, modelling and testing. The speaker identification performance depends on the techniques employed in these stages. As demonstrated by different experiments, in case of limited training and testing data condition, owing to less data, existing techniques in each stage will not provide good performance. This work demonstrates the following: multiple frame size and rate (MFSR) analysis provides improvement in the analysis stage, combination of mel frequency cepstral coefficients (MFCC), its temporal derivatives $(\\Delta,\\Delta \\Delta)$, linear prediction residual (LPR) and linear prediction residual phase (LPRP) features provides improvement in the feature extraction stage and combination of learning vector quantization (LVQ) and gaussian mixture model – universal background model (GMM–UBM) provides improvement in the modelling stage. The performance is further improved by integrating the proposed techniques at the respective stages and combining the evidences from them at the testing stage. To achieve this, we propose strength voting (SV), weighted borda count (WBC) and supporting systems (SS) as combining methods at the abstract, rank and measurement levels, respectively. Finally, the proposed hierarchical combination (HC) method integrating these three methods provides significant improvement in the performance. Based on these explorations, this work proposes a scheme for speaker identification under limited training and testing data.

  5. MicroRNA-mediated signal amplification coupled with GNP/dendrimers on a mass-sensitive biosensor and its applications in intracellular microRNA quantification.

    Science.gov (United States)

    Guo, Yingshu; Wang, Yujie; Yang, Guangxu; Xu, Jing-Juan; Chen, Hong-Yuan

    2016-11-15

    Here, a mass-sensitive microRNA sensing surface is developed by utilizing a probe DNA/gold nanoparticles (GNP)/dendrimer composite coupling with an enzymatic amplification process. The probe DNA/GNP/dendrimer composite is prepared via the covalent coupling between the NH2 groups in PAMAM or DNA and the COOH group on GNP. Target microRNA binds to a stem-loop-structured DNA on maganatic NPs, forming a heteroduplex. By enzyme recycling amplification, a large number of linker sequences are produced on MNPs. Via the combination of probe DNA, the linker DNA on MNPs and a capture DNA on gold chip, the DNA/GNP/dendrimer probe could be assembled on the surface of gold chip inducing a sensitive frequency response. It presents an excellent performance in microRNA-203 quantification with a detection linear range of 1.0×10(-11)-1.0×10(-9)M. Both the success in discriminating expressing miroRNA-203 in MCF-7 cell and the well agreement with the commercial qRT-PCR detection method implied its potential application in early cancer diagnosis for future. PMID:27311115

  6. The Preparation and Application of Dendrimer Modified CdTe/CdS Near Infrared Quantum Dots for Brain Cancer Cells Imaging

    Directory of Open Access Journals (Sweden)

    Qingke Bai

    2015-11-01

    Full Text Available The most notable obstacle of brain cancer diagnosis is the inability of delivering imaging agents across the blood-brain barrier (BBB. Recently, quantum dots (QDs has been demonstrated as an ideal image agent for brain imaging due to their ultra-small size for crossing BBB. The plolyamidoamine dendrimers modified CdTe/CdS core/shell near-infrared (NIR region QDs was successfully synthesized in aqueous solution, and then was characterized by UV-vis absorption, photoluminescence (PL spectroscopy, dynamic light scattering (DLS, X-ray powder diffraction (XRD and high-resolution transmission electron microscopy (HR-TEM, etc. Our results reveal that the dendrimers modified CdTe/CdS QDs exhibits good water-dispersity and stable NIR fluorescence in various biological environments. In addition, this NIR QDs demonstrates a good biocompatibility and sensitive photoluminescence responses in brain tumor cell imaging. In a word, this type of dendrimers modified NIR CdTe/CdS QDs has huge potential applications in brain imaging.

  7. Alkali cation specific adsorption onto fcc(111) transition metal electrodes.

    Science.gov (United States)

    Mills, J N; McCrum, I T; Janik, M J

    2014-07-21

    The presence of alkali cations in electrolyte solutions is known to impact the rate of electrocatalytic reactions, though the mechanism of such impact is not conclusively determined. We use density functional theory (DFT) to examine the specific adsorption of alkali cations to fcc(111) electrode surfaces, as specific adsorption may block catalyst sites or otherwise impact surface catalytic chemistry. Solvation of the cation-metal surface structure was investigated using explicit water models. Computed equilibrium potentials for alkali cation adsorption suggest that alkali and alkaline earth cations will specifically adsorb onto Pt(111) and Pd(111) surfaces in the potential range of hydrogen oxidation and hydrogen evolution catalysis in alkaline solutions.

  8. Interference of cationic polymeric nanoparticles with clinical chemistry tests--clinical relevance.

    Science.gov (United States)

    Shcharbin, Dzmitry; Shcharbina, Natallia; Milowska, Katarzyna; de la Mata, Francisco Javier; Muñoz-Fernandez, Maria Angeles; Mignani, Serge; Gomez-Ramirez, Rafael; Majoral, Jean-Pierre; Bryszewska, Maria

    2014-10-01

    The development of medical nanosystems requires knowledge of their behavior in vivo. Clinical chemistry tests are widely used to estimate the systemic toxicity of nanoparticles. In this paper we have explored the impact of small positively charged nanoparticles-poly(amidoamine), phosphorous and carbosilane dendrimers - on biochemical parameters of standardized serum in vitro. All the dendrimers could shift the main biochemical parameters. Thus, in the case of patients having the normal, but 'boundary', values of biochemical parameters, nanoparticle-induced changes can be wrongly interpreted as evidence of some dysfunctions (hepatic, renal, etc.). Moreover, the effects of nanoparticles of metals, carbon nanotubes, quantum dots, fullerenes, dendrimers having been sized up to 4000 nm and the hundreds of reactive groups, can be significantly higher. Thus, preliminary evaluation of any nanomaterial in vitro is required in clinical chemistry tests before its application in vivo to draw the correct conclusions and benefit animals.

  9. Synthesis and Characterization of Poly-L-Lysine Dendrimers%树枝状聚赖氨酸的合成及表征

    Institute of Scientific and Technical Information of China (English)

    刘卅; 董红霞; 郭建维

    2011-01-01

    Using a hexamethylene diamine as initiator core,Nα,Nε-di-t-BOC-L-lysine dicyclohexylammonium salt(Boc-L-Lys(Boc)-OH·DCHA)as raw material,t-Boc-protected poly-L-lysine dendrimers were designed and divergently synthesized by solution phase peptide chemistry,then t-Boc groups were removed by trifluoroacetic acid(TFA).Poly-L-lysine dendrimers were obtained in high purity.The structures of the products were further characterized by 1H-NMR spectroscopy,13C-NMR spectroscopy,electrospray ionization mass spectrometry(ESI-MS) and matrix-assisted laser desorption time of flight mass spectrometry(MALDI-TOF MS).The results represent the consistency for products with the target poly-L-lysine dendrimers.Monodispersed dendritic poly-L-lysine dendrimers of first and fourth generations were obtained in high yield(60%~80%).Due to many advantages of poly-L-lysine dendrimers relative to linear polypeptides,their applications are considered to be prospective in biochemistry,molecular biology,and chemistry biology field.%以己二胺为核,L-2,6-二叔丁氧羰基赖氨酸.二环己胺盐(Boc-L-Lys(Boc)-OH.DCHA)为原料,在均相反应条件下采用发散法设计合成了t-Boc保护的树枝状聚赖氨酸,然后用三氟乙酸切割保护基团获得高纯度的树枝状聚赖氨酸。利用核磁共振(1H-NMR、13C-NMR)和基质辅助激光解析串联飞行时间质谱(MALDI-TOF MS)等手段对所得产物结构进行了表征。分析结果表明,采用1-羟基苯丙三氮唑(HOBT)和苯并三氮唑-N,N,N’,N’-四甲基脲六氟磷酸盐(HBTU)作为缩合剂,在25℃缩合24 h、三氟乙酸溶液(TFA∶DCM=95∶5)室温切割1.5 h,合成了一至四代结构规整的树枝状聚赖氨酸,产率介于60%~80%之间。

  10. 超支化聚酰胺-胺防沾色剂的合成及性能初探%Synthesis and application of hyperbranched polyamidoamine anti-staining agent

    Institute of Scientific and Technical Information of China (English)

    尹黎; 沈安京; 车映红

    2011-01-01

    A novel kind of water-soluble hyperbranched polymer, the amino-terminated hyperbranched polyamidoamine(HPAMAM-NH2) , is synthesized by the Michael addition and melt polymerization of methyl acrylate ( MA ) and diethylenetriamine ( DTA) . HPAMAM is added to the selected ten kinds of water-soluble dyes solution separately. The flocculated dye prevents the dye and fiber from combining , the removal of loose color and anti-staining effect are achieved. Taking reactive orange K-GN as an example , satisfying anti - staining result is achieved under the condition of pH value 5 ~ 6, with little dosage of HPAMAM ( < 10 g/L) at 30 ℃ for 15 ~ 30 min.%采用丙烯酸甲酯(MA)与二乙烯基三胺(DTA)为主要原料,采用Michael(麦克尔)加成和熔融聚合两步法合成了一种水溶性的超支化聚合物端氨基超支化聚酰胺-胺(HPAMAM-NH2).选用10种水溶性染料,配成染液,加入该超支化聚合物后可使染料絮凝,阻止染料与纤维结合,从而达到去除浮色和防沾色效果.以活性橙K-GN为代表,在30℃,pH值为5~6的条件下用少量HPAMAM(<10 g/L)处理15~30 min,能达到良好的防沾色效果.

  11. 基于纳米银/石墨烯/酪氨酸酶/聚酰胺-胺的双酚A传感器%Bisphenol A biosensor based on glassy carbon electrode modified with Ag nanoparticles, graphene, tyrosinase and polyamidoamine

    Institute of Scientific and Technical Information of China (English)

    郭倩琼; 王炜祺; 高佩怡; 马腾飞; 杨乐乐; 黄杉生

    2014-01-01

    采用石墨烯纳米材料,并结合酪氨酸酶、聚酰胺-胺(PAMAM)和纳米银修饰玻碳电极研制了新型BPA生物传感器。运用循环伏安法和电化学交流阻抗考察了修饰电极的电化学行为。由于石墨烯独特的物理化学性质,结合聚酰胺-胺和纳米银的协同作用,该修饰电极对于BPA有较好的电流响应。在最佳条件下,该传感器对双酚A的线性检测范围为1.0×10-7~3.3×10-5 mol/L,检测限为3.0×10-8 mol/L(信噪比为3),相关系数为0.998。%A bisphenol A biosensor based on Ag nanoparticles, graphene, tyrosinase and polyamidoamine (PAMAM) modified electrode was prepared. The electrochemical behavior of the BPA biosensor was investigated by cyclic voltammetry and electrochemical impedance spectroscopy. Owning to the special physicochemical characteristic of the nanomaterials and the synergism between Ag nanoparticles and PAMAM, the sensor showed good amperometric response towards BPA. Under the optimal experimental conditions, the current is linear with the concentration of BPA in the range from 1.0 ×10-7 to 3.3 ×10-5 mol/L, with a detection limit of 3.0×10-8 mol/L (S/N = 3) and a correlation coefficient of 0.998.

  12. POSS基树枝状大分子的合成与应用%Synthesis and Application of Dendrimers Based on Polyhedral Oligomeric Silsesquioxanes

    Institute of Scientific and Technical Information of China (English)

    姚敏; 王嘉骏; 顾雪萍; 冯连芳

    2012-01-01

    Dendrimer is one type of macromolecules with well-defined, highly-branched and nano-scaled architectures, composed of three distinct domains: core, branches and terminal groups. Its potential functions and applications are explored based on the unique physical and chemical features due to special molecular architecture. Using polyhedral oligomerie silsesquioxanes (POSS) as the core of dendrimers is an effective and facile way to simplify the tedious repetitive steps of preparation and separation. Since POSS allows eight branches to radiate from a silicon-oxygen rigid cubic core, the dendrimers can be constructed in a well-controlled globular, three- dimensional framework, and large numbers of peripheral groups can be obtained at relatively low generation numbers. As a kind of novel nano-hybrid supermolecules, POSS-based dendrimers have attracted considerable interest in materials science. In this review, we briefly introduce the synthetic approaches of some typical POSS- based dendrimers categorized by the different chemical composition of branching units, and then focus on the potential functions and applications of this nano-hybrid material in the fields of catalysis, gene and drug delivery, liquid crystals, light harvesting and energy transfer. The specific and excellent properties imparted by the incorporation of POSS into dendrimers are also presented. Finally, the advances of POSS-based dendrimers are prospected.%树枝状大分子(dendrimer)是一种高度支化、纳米尺度的人工合成大分子,具有独特的物理化学性能和重要的应用前景。利用具有8个可官能化顶点的多面体低聚倍半硅氧烷(POSS)作为树枝状大分子的核心,可在一定程度上简化树枝状大分子繁琐的合成与分离过程,在低代数时就可获得较大的表面官能团密度,并使树枝状分子呈现球形对称结构。POSS基树枝状大分子结合了POSS和树枝状分子结构与性能的优势,是一类

  13. Complex Macromolecular Architectures by Living Cationic Polymerization

    KAUST Repository

    Alghamdi, Reem D.

    2015-05-01

    Poly (vinyl ether)-based graft polymers have been synthesized by the combination of living cationic polymerization of vinyl ethers with other living or controlled/ living polymerization techniques (anionic and ATRP). The process involves the synthesis of well-defined homopolymers (PnBVE) and co/terpolymers [PnBVE-b-PCEVE-b-PSiDEGVE (ABC type) and PSiDEGVE-b-PnBVE-b-PSiDEGVE (CAC type)] by sequential living cationic polymerization of n-butyl vinyl ether (nBVE), 2-chloroethyl vinyl ether (CEVE) and tert-butyldimethylsilyl ethylene glycol vinyl ether (SiDEGVE), using mono-functional {[n-butoxyethyl acetate (nBEA)], [1-(2-chloroethoxy) ethyl acetate (CEEA)], [1-(2-(2-(t-butyldimethylsilyloxy)ethoxy) ethoxy) ethyl acetate (SiDEGEA)]} or di-functional [1,4-cyclohexanedimethanol di(1-ethyl acetate) (cHMDEA), (VEMOA)] initiators. The living cationic polymerizations of those monomers were conducted in hexane at -20 0C using Et3Al2Cl3 (catalyst) in the presence of 1 M AcOEt base.[1] The PCEVE segments of the synthesized block terpolymers were then used to react with living macroanions (PS-DPE-Li; poly styrene diphenyl ethylene lithium) to afford graft polymers. The quantitative desilylation of PSiDEGVE segments by n-Bu4N+F- in THF at 0 °C led to graft co- and terpolymers in which the polyalcohol is the outer block. These co-/terpolymers were subsequently subjected to “grafting-from” reactions by atom transfer radical polymerization (ATRP) of styrene to afford more complex macromolecular architectures. The base assisted living cationic polymerization of vinyl ethers were also used to synthesize well-defined α-hydroxyl polyvinylether (PnBVE-OH). The resulting polymers were then modified into an ATRP macro-initiator for the synthesis of well-defined block copolymers (PnBVE-b-PS). Bifunctional PnBVE with terminal malonate groups was also synthesized and used as a precursor for more complex architectures such as H-shaped block copolymer by “grafting-from” or

  14. Aggregate Formed by a Cationic Fluorescence Probe

    Institute of Scientific and Technical Information of China (English)

    TIAN, Juan; SANG, Da-Yong; JI, Guo-Zhen

    2007-01-01

    The aggregation behavior of a cationic fluorescence probe 10-(4,7,10,13,16-pentaoxa-1-azacyclooctadecyl-methyl)anthracen-9-ylmethyl dodecanoate (1) was observed and studied by a fluorescence methodology in acidic and neutral conditions. By using the Py scale, differences between simple aggregates and micelles have been discussed. The stability of simple aggregates was discussed in terms of hydrophobic interaction and electrostatic repulsion. The absence of excimer emission of the anthrancene moiety of probe 1 in neutral condition was attributed to the photoinduced electron transfer mechanism instead of photodimerization.

  15. Cationic Antimicrobial Polymers and Their Assemblies

    Directory of Open Access Journals (Sweden)

    Ana Maria Carmona-Ribeiro

    2013-05-01

    Full Text Available Cationic compounds are promising candidates for development of antimicrobial agents. Positive charges attached to surfaces, particles, polymers, peptides or bilayers have been used as antimicrobial agents by themselves or in sophisticated formulations. The main positively charged moieties in these natural or synthetic structures are quaternary ammonium groups, resulting in quaternary ammonium compounds (QACs. The advantage of amphiphilic cationic polymers when compared to small amphiphilic molecules is their enhanced microbicidal activity. Besides, many of these polymeric structures also show low toxicity to human cells; a major requirement for biomedical applications. Determination of the specific elements in polymers, which affect their antimicrobial activity, has been previously difficult due to broad molecular weight distributions and random sequences characteristic of radical polymerization. With the advances in polymerization control, selection of well defined polymers and structures are allowing greater insight into their structure-antimicrobial activity relationship. On the other hand, antimicrobial polymers grafted or self-assembled to inert or non inert vehicles can yield hybrid antimicrobial nanostructures or films, which can act as antimicrobials by themselves or deliver bioactive molecules for a variety of applications, such as wound dressing, photodynamic antimicrobial therapy, food packing and preservation and antifouling applications.

  16. Cobalt 60 cation exchange with mexican clays

    International Nuclear Information System (INIS)

    Mexican clays can be used to remove radioactive elements from contaminated aqueous solutions. Cation exchange experiments were performed with 60 Co radioactive solution. In the present work the effect of contact time on the sorption of Co 2+ was studied. The contact time in hydrated montmorillonite was from 5 to 120 minutes and in dehydrated montmorillonite 5 to 1400 minutes. The Co 2+ uptake value was, in hydrated montmorillonite, between 0.3 to 0.85 m eq/g and in dehydrated montmorillonite, between 0.6 to 1.40 m eq/g. The experiments were done in a pH 5.1 to 5.7 and normal conditions. XRD patterns were used to characterize the samples. The crystallinity was determined by X-ray Diffraction and it was maintained before and after the cation exchange. DTA thermo grams showed the temperatures of the lost humidity and crystallization water. Finally, was observed that dehydrated montmorillonite adsorb more cobalt than hydrated montmorillonite. (Author)

  17. Photodissociation of Cerium Oxide Nanocluster Cations.

    Science.gov (United States)

    Akin, S T; Ard, S G; Dye, B E; Schaefer, H F; Duncan, M A

    2016-04-21

    Cerium oxide cluster cations, CexOy(+), are produced via laser vaporization in a pulsed nozzle source and detected with time-of-flight mass spectrometry. The mass spectrum displays a strongly preferred oxide stoichiometry for each cluster with a specific number of metal atoms x, with x ≤ y. Specifically, the most prominent clusters correspond to the formula CeO(CeO2)n(+). The cluster cations are mass selected and photodissociated with a Nd:YAG laser at either 532 or 355 nm. The prominent clusters dissociate to produce smaller species also having a similar CeO(CeO2)n(+) formula, always with apparent leaving groups of (CeO2). The production of CeO(CeO2)n(+) from the dissociation of many cluster sizes establishes the relative stability of these clusters. Furthermore, the consistent loss of neutral CeO2 shows that the smallest neutral clusters adopt the same oxidation state (IV) as the most common form of bulk cerium oxide. Clusters with higher oxygen content than the CeO(CeO2)n(+) masses are present with much lower abundance. These species dissociate by the loss of O2, leaving surviving clusters with the CeO(CeO2)n(+) formula. Density functional theory calculations on these clusters suggest structures composed of stable CeO(CeO2)n(+) cores with excess oxygen bound to the surface as a superoxide unit (O2(-)). PMID:27035210

  18. Ground state of naphthyl cation: Singlet or triplet?

    Energy Technology Data Exchange (ETDEWEB)

    Dutta, Achintya Kumar; Vaval, Nayana, E-mail: np.vaval@ncl.res.in; Pal, Sourav, E-mail: s.pal@ncl.res.in [Physical Chemistry Division, CSIR-National Chemical Laboratory, Pune 411008 (India); Manohar, Prashant U. [Department of Chemistry, BITS Pilani, Pilani Campus (India)

    2014-03-21

    We present a benchmark theoretical investigation on the electronic structure and singlet-triplet(S-T) gap of 1- and 2-naphthyl cations using the CCSD(T) method. Our calculations reveal that the ground states of both the naphthyl cations are singlet, contrary to the results obtained by DFT/B3LYP calculations reported in previous theoretical studies. However, the triplet states obtained in the two structural isomers of naphthyl cation are completely different. The triplet state in 1-naphthyl cation is (π,σ) type, whereas in 2-naphthyl cation it is (σ,σ{sup ′}) type. The S-T gaps in naphthyl cations and the relative stability ordering of the singlet and the triplet states are highly sensitive to the basis-set quality as well as level of correlation, and demand for inclusion of perturbative triples in the coupled-cluster ansatz.

  19. Influence of interlayer cations on organic intercalation of montmorillonite.

    Science.gov (United States)

    Wu, Limei; Liao, Libing; Lv, Guocheng

    2015-09-15

    The influence of the types of interlayer cations on organic intercalation of montmorillonite (Mt) was studied in this paper. The distribution of Na(+), K(+), Mg(2+), Ca(2+) and Fe(3+) in montmorillonite interlayer, their interaction with structure layers and the effect of interlayer cations on the basal spacing of Mt, the amount of binding water for different interlayer cations and the binding force between them were investigated systematically. 1-Hexadecy1-3-methylimidazolium chloride monohydrate (C16mimCl) was intercalated into montmorillonites with different interlayer cations. The influence of interlayer cations on organic intercalation was investigated. Molecular dynamics (MD) modeling was used to speculate the interlayer microstructures of the organically intercalated Mt with different interlayer cations. These simulations help to predict the microstructure of organo-Mt and guide their relevant engineering applications. PMID:26001131

  20. Bespoke cationic nano-objects via RAFT aqueous dispersion polymerisation

    OpenAIRE

    Williams, M.; Penfold, NJW; Lovett, JR; Warren, NJ; Douglas, CWI; Doroshenko, N; Verstraete, P; Smets, J; Armes, SP

    2016-01-01

    A range of cationic diblock copolymer nanoparticles are synthesised via polymerisation-induced self-assembly (PISA) using a RAFT aqueous dispersion polymerisation formulation. The cationic character of these nanoparticles can be systematically varied by utilising a binary mixture of two macro-CTAs, namely non-ionic poly(glycerol monomethacrylate) (PGMA) and cationic poly[2-(methacryloyloxy)ethyl]trimethylammonium chloride (PQDMA), with poly(2-hydroxypropyl methacrylate) (PHPMA) being selected...