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Sample records for cationic polyamidoamine dendrimer

  1. A novel Ag+ cation sensor based on polyamidoamine dendrimer modified with 1,8-naphthalimide derivatives

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    Dodangeh, Mohammad; Gharanjig, Kamaladin; Arami, Mokhtar

    2016-02-01

    In this study, 4-amino-1,8-naphthalimide-conjugated polyamidoamine dendrimer was synthesized and characterized and its potentiality as a cation sensor was investigated. 4-Amino-1,8-naphthalic anhydride reacted with polyamidoamine dendrimer and the product was characterized using FTIR, 1H NMR, 13C NMR and melting point analysis method. The synthesized compound was applied to detect various cations in water media and N,N-dimethylformamide (DMF) via monitoring the quenching of the fluorescence intensity. Furthermore, various metal cations including Cu2 +, Ni2 +, Zn2 +, Pb2 +,Ca2 +, Ba2 +, Cd2 +, Hg2 +, Fe2 +, Fe3 + and Ag+ were tested. The complexes formed between the synthesized compound and metal cations in solution and their effects on Photoinduced Electron Transfer (PET) process were investigated regarding the potential application of the newly-synthesized dendrimer as a colorimetric and fluorescent sensor for such cations. The results clearly confirmed that the 1,8-naphthalimide groups surrounding the central dendrimer core showed strong green fluorescence emission at 553 nm. This effect considerably decreased with the introduction of all cations, except Ag+ where the fluorescence quenching effect was remarkable and more dominant. Therefore, it can be concluded that the synthesized dye has the potentiality of being a highly sensitive and selective fluorescence sensor for Ag+ cation.

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

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    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. [Advancement of research on polyamidoamine dendrimers].

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    Xu, Jing; Zhang, Longzhen

    2012-10-01

    Polyamidoamine (PAMAM) dendrimers is synthesized by the American scientist, Tomalia, in 1985 and is now used widely in many fields such as gene carriers, photoelectric sensor, wastewater treatment, drug carriers and catalyst. The present paper mainly reviews the structure and methods of synthesis, celluar cytotoxicity, achievements of gene and drug carriers research, advancement and prospect of PAMAM as a carrier in glioma therapy. Besides, it also involves an outline for the future research of the radiotherapy for glioma.

  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. Synthesis and properties of new amphoteric poly(amidoamine dendrimers

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    2009-08-01

    Full Text Available A series of new amphoteric dendrimers have been synthesized by attaching dimethylbenzylaminoethyl acrylate chloride (Bz80, sodium acrylic acid (SAA and modified polyoxyethylene (MPEO units to a third-generation poly(amidoamine (PAMAM dendrimer core via Michael addition reaction. The structure of the dendrimers was confirmed by Fourier transform infrared (FTIR, proton nuclear magnetic resonance (1H NMR, carbon 13 nuclear magnetic resonance (13C NMR spectroscopy and by elemental analysis. Thermal stability and intrinsic viscosity were investigated. The applicable experiment exhibited the amphoteric dendrimers have high flocculation efficiency, which could be significantly improved by combining amphoteric dendrimers with polyacrylamide (PAM. The suitable mass ratio of the dendrimers and PAM was 2:3. The study would promote the use of amphoteric dendrimers as a flocculant in treating wastewater and as a new paper retention aid in papermaking.

  9. Cationic PAMAM dendrimers aggressively initiate blood clot formation.

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    Jones, Clinton F; Campbell, Robert A; Brooks, Amanda E; Assemi, Shoeleh; Tadjiki, Soheyl; Thiagarajan, Giridhar; Mulcock, Cheyanne; Weyrich, Andrew S; Brooks, Benjamin D; Ghandehari, Hamidreza; Grainger, David W

    2012-11-27

    Poly(amidoamine) (PAMAM) dendrimers are increasingly studied as model nanoparticles for a variety of biomedical applications, notably in systemic administrations. However, with respect to blood-contacting applications, amine-terminated dendrimers have recently been shown to activate platelets and cause a fatal, disseminated intravascular coagulation (DIC)-like condition in mice and rats. We here demonstrate that, upon addition to blood, cationic G7 PAMAM dendrimers induce fibrinogen aggregation, which may contribute to the in vivo DIC-like phenomenon. We demonstrate that amine-terminated dendrimers act directly on fibrinogen in a thrombin-independent manner to generate dense, high-molecular-weight fibrinogen aggregates with minimal fibrin fibril formation. In addition, we hypothesize this clot-like behavior is likely mediated by electrostatic interactions between the densely charged cationic dendrimer surface and negatively charged fibrinogen domains. Interestingly, cationic dendrimers also induced aggregation of albumin, suggesting that many negatively charged blood proteins may be affected by cationic dendrimers. To investigate this further, zebrafish embryos were employed to more specifically determine the speed of this phenomenon and the pathway- and dose-dependency of the resulting vascular occlusion phenotype. These novel findings show that G7 PAMAM dendrimers significantly and adversely impact many blood components to produce rapid coagulation and strongly suggest that these effects are independent of classic coagulation mechanisms. These results also strongly suggest the need to fully characterize amine-terminated PAMAM dendrimers in regard to their adverse effects on both coagulation and platelets, which may contribute to blood toxicity.

  10. Investigation of the interaction of polyamidoamine dendrimers with nicotinic acid as solubility enhancer

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective Polyamidoamine(PAMAM) dendrimers enhance the solubility of nicotinic acid. Methods PAMAM dendrimers of generation 1 to 6 were prepared and the effect of pH and concentration of the dendrimers on the solubility enhancement of nicotinic acid was investigated. Results The pH and concentration of the dendrimers influence the solubility enhancement of nicotinic acid. Conclusions Electrostatic interaction between the carboxyl group of the nicotinic acid and the amine groups of the dendrimers is involved.

  11. 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

  12. 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.

  13. Functional properties of fluorescent poly(amidoamine) dendrimers in nematic liquid crystalline media

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    Grabchev, Ivo; Sali, Seher; Chovelon, Jean-Marc

    2006-05-01

    The effectiveness of poly(amidoamine) dendrimers from zero generation as a fluorescent guest for liquid crystal displays of the 'guest-host' type is discussed on the basis of their absorption and fluorescent properties. It has been shown that the dendrimers at concentration of 0.3 wt% do not destabilize the orientation of the liquid crystal matrix. The orientation order parameters SA and SF depends on the nature of the substituent at C-4 position of the 1,8-naphthalimide. The effect that poly(amidoamine) dendrimers have upon the phase transition temperature and the electro-optical properties of the LC/dendrimer mixtures has been also presented. All investigations reported have been carried out in surface stabilized display cells.

  14. Kinetic and thermodynamic study of the transfer of anionic polyamidoamine dendrimers across two immiscible liquids

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    Gonzalez-Fuentes, Miguel A.; Manriquez, J.; Antano-Lopez, R. [Centro de Investigacion y Desarrollo Tecnologico en Electroquimica S.C., Parque Tecnologico Queretaro Sanfandila, P.O. Box 064, Pedro Escobedo 76703, Queretaro (Mexico); Godinez, Luis A., E-mail: lgodinez@cideteq.mx [Centro de Investigacion y Desarrollo Tecnologico en Electroquimica S.C., Parque Tecnologico Queretaro Sanfandila, P.O. Box 064, Pedro Escobedo 76703, Queretaro (Mexico)

    2011-10-01

    The kinetics and thermodynamics for the phase transfer of carboxyl-terminated polyamidoamine (PAMAM) dendrimers across the water/dichloroethane interface were analyzed by cyclic voltammetry and electrochemical impedance spectroscopy. A three phase junction was employed by inserting a cylindrical gold electrode through the liquid-liquid interface. The reversible redox species decamethylferrocene (DMFc) was used in the organic phase in order to promote dendrimer transfer. It was found that the electrochemical behaviour of DMFc at the gold/dichloroethane interface depends on the generation and concentration of the dendrimer species in the aqueous phase. In addition, it was observed that the electrochemically driven transfer of these macromolecules corresponds to a quasi-reversible process. The data obtained from thermodynamic studies indicate that dendrimers are transferred between the two phases under study by an entropy controlled process.

  15. 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.

  16. Synthesis and Characterization of Poly(Amidoamine Dendrimers Encapsulatd 198Au Nanoparticles

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    R. Ritawidya1,2

    2012-12-01

    Full Text Available Brachytherapy or internal radiotherapy is one of many methods used for treatment of cancer. This modality requires an agent with radionuclides that emits  or β particle with a proper energy. 198Au (99% β max = 0.96 MeV and t1/2 = 2.69 days is one of radionuclides that has been considered to be effective for the above-mentioned purpose. The purpose of this research was to synthesis and characterize poly(amidoamine (PAMAM G3.0 dendrimers encapsulated 198Au nanoparticles as a new brachytherapy agent. PAMAM G3.0 dendrimers encapsulated 198Au nanoparticles was successfully synthesized by a bottom-up method using sodium borohydride as a reductor. Purification was then performed by a size exclusion chromatography in order to separate large Au nanoparticles that were formed outside the cavity of PAMAM G3.0 dendrimers. Prior to the synthesis of PAMAM G3.0 dendrimers encapsulated 198Au nanoparticles, the synthetic procedure was first established by using a non-radioactive Au. The PAMAM G3.0 dendrimers encapsulated Au nanoparticles produced was then characterized by using an UV-Vis spectroscopy, a transmission electron microscopy (TEM, particle size analyzer (PSA, and an atomic absorption spectroscopy (AAS. Characterization results revealed that PAMAM G3.0 dendrimers encapsulated Au nanoparticles that were prepared from a reaction mixture of PAMAM G3.0 dendrimers and Au HAuCl4 with mol ratio of 2.8, was found to be a proper formula. It produced PAMAM G3.0 dendrimers encapsulated Au nanoparticles with diameter of 1.743 nm, spheris, uniform and drug loading value of 26.34%. This formula was then used in synthesis using radioactive Au, 198Au. Characterization results of PAMAM G3.0 dendrimers encapsulated 198Au nanoparticles gave a radiochemical purity of 99.4% and zero charge.

  17. Evaluation of polyamidoamine dendrimers as potential carriers for quercetin, a versatile flavonoid.

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    Madaan, Kanika; Lather, Viney; Pandita, Deepti

    2016-01-01

    The aim of the present research work was to investigate the potential of polyamidoamine (PAMAM) dendrimers as oral drug delivery carriers for quercetin, a Biopharmaceutical Classification System (BCS) class II molecule. The aqueous solubility of quercetin was investigated in different generations of dendrimers, i.e. G0, G1, G2 and G3, with varying concentrations (0.1, 0.5, 1, 2 and 4 µM). Then, it was successfully incorporated in PAMAM dendrimers and they were characterized for incorporation efficacy, nature of nanoformulations, size, size distribution, surface morphology and stability. In vitro release characteristics of quercetin from all quercetin-PAMAM complexes were studied at 37 °C in phosphate buffer saline (PBS; pH 7.4). Furthermore, the efficacy of quercetin-loaded PAMAM dendrimer was assessed by pharmacodynamic experiment, namely, a carrageenan-induced paw edema model to evaluate the acute activity of this nanocarrier in response to inflammation. It was observed that both generation and the respective concentrations of PAMAM dendrimers showed potential positive effects on solubility enhancement of quercetin. All the quercetin-PAMAM complexes were found to be in nanometeric range (quercetin which was characterized by an initial faster release followed by sustained release phase and pharmacodynamic study provided the preliminary proof of concept about the potential of quercetin-PAMAM complexes. The study concludes that the dendrimer-based drug delivery system for quercetin has enormous potential to resolve the drug delivery issues associated with it.

  18. 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.

  19. Aggregation-controlled excimer emission from anthracene-containing polyamidoamine dendrimers.

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    Lekha, P K; Prasad, Edamana

    2010-03-22

    Lower generations of polyamidoamine (PAMAM) dendrimers were peripherally modified with anthracene moieties, and excimer emission from anthracene chromophores was investigated in an acetonitrile-water mixture at acidic and basic pH values. Results from fluorescence spectroscopic experiments suggest that 1) the propensity of anthracene-modified PAMAM dendrimers to aggregate in acetonitrile is substantial in the presence of 15-20 vol % of water, and 2) aggregate formation in anthracene-modified PAMAM dendrimers leads to unique morphologies in the ground state, where the anthracene units are pre-arranged to form stable excimers upon photoexcitation. Three types of anthracene excimers are generated in the system, with face-to-face, angular, and T-shaped geometry. The formation of different types of anthracene excimers was confirmed by steady-state and time-resolved fluorescence spectroscopic experiments. Experimental results further suggest that it is feasible to alter the type of excimer formed by anthracene units attached to the PAMAM dendrimers through altering the propensity for ground-state aggregation. Most excitingly, increased pi conjugation in the molecular framework of anthracene-substituted PAMAM dendrimers leads to intense and exclusive excimer emission from anthracene at room temperature.

  20. Direct TLC/MALDI-MS coupling for modified polyamidoamine dendrimers analyses.

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    Leriche, Emma-Dune; Hubert-Roux, Marie; Grossel, Martin C; Lange, Catherine M; Afonso, Carlos; Loutelier-Bourhis, Corinne

    2014-01-15

    Polyamidoamine (PAMAM) are synthetic dendrimers which present attractive properties for the biological and biomedical fields, as they proved to be efficient drug and gene carriers. In order to increase their transfection efficiency, chemical modifications of the amino end-groups had been reported. In this work, the synthesis of the ammonia-cored G1(N) PAMAM and the consecutive chemical modification with glycine or phenylalanine amino-acids were monitored using the coupling of thin layer chromatography (TLC) with matrix-assisted laser desorption ionization-mass spectrometry (MALDI-MS). Thus, the monitoring of the PAMAM synthesis included the identification of the by-products such as defective structures of PAMAM dendrimers as well as the study of phenylalanine-grafted PAMAM oligomer distribution.

  1. 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.

  2. 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

  3. Growth of multi-amine terminated poly(amidoamine) dendrimers on the surface of carbon nanotubes

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    Pan, Bifeng; Cui, Daxiang; Gao, Feng; He, Rong

    2006-05-01

    An in situ repetitive divergent polymerization strategy was employed to grow multi-amine poly(amidoamine) dendritic macromolecules on the surfaces of multiwalled carbon nanotubes (MWNTs), affording novel three-dimensional (3D) molecular nanocomposites. The crude MWNTs were oxidized using H2SO4/HNO3 = 3:1 (v/v) and then reacted with thionyl chloride, resulting in MWNTs functionalized with chlorocarbonyl groups (MWNT-COCl). MWNT-COCl, when reacted with an excess of ethylenediamine, produced amine-functionalized MWNT supported initiators (MWNT-NH2). Using the MWNT-NH2 as the growth supporter and methylacrylate/ethylenediamine as building blocks, multi-amine dendritic poly(amidoamine) macromolecules were covalently grafted onto the sidewalls and ends of MWNTs via Michael addition reaction and amidation. Thermal gravimetric analysis (TGA) measurements showed that the weight ratio of the as-grown dendritic polymers on the MWNT surfaces lay in the 10%-50% range. The products were also characterized by Fourier transform infrared (FTIR), Raman, nuclear magnetic resonance (NMR), and transmission electron microscopy (TEM) analysis. The results indicate that the dendrimers are grafted onto the surface of MWNTs. The as-prepared nanocomposites exhibit excellent dispersibility in water.

  4. Tumor targeting using polyamidoamine dendrimer-cisplatin nanoparticles functionalized with diglycolamic acid and herceptin.

    Science.gov (United States)

    Kesavan, Akila; Ilaiyaraja, P; Sofi Beaula, W; Veena Kumari, Vuttaradhi; Sugin Lal, J; Arunkumar, C; Anjana, G; Srinivas, Satish; Ramesh, Anita; Rayala, Suresh Kumar; Ponraju, D; Venkatraman, Ganesh

    2015-10-01

    Polymer mediated drug delivery system represents a novel promising platform for tumor-targeting with reduced systemic side effects and improved chemotherapeutical efficacy. In this study, we report the preparation and characterization of herceptin targeted, diglycolamic acid (DGA) functionalized polyamidoamine (PAMAM) dendrimer as a potent drug carrier for cisplatin. DGA dendrimers carrying cisplatin demonstrated enhanced anticancer activity when targeted with herceptin. In vitro cell line studies with herceptin-DGA-G4-cisplatin in HER-2 +ve and HER-2 -ve human ovarian cancer cell lines showed that these nanoparticles possessed remarkable features such as lower IC50 value, improved S-phase arrest, and enhanced apoptosis due to increased cellular uptake and accumulation than the untargeted DGA-G4-cisplatin and free cisplatin. Furthermore, in vivo results in SCID mice bearing SKOV-3 tumor xenografts, herceptin-DGA-G4-cisplatin, appeared to be more effective in inducing tumor regression as compared to free cisplatin. Collectively, these results indicate that herceptin targeted DGA functionalized PAMAM-cisplatin conjugates serve as better anti-tumor agents than individual therapeutic agents.

  5. Generation 9 polyamidoamine dendrimer encapsulated platinum nanoparticle mimics catalase size, shape, and catalytic activity.

    Science.gov (United States)

    Wang, Xinyu; Zhang, Yincong; Li, Tianfu; Tian, Wende; Zhang, Qiang; Cheng, Yiyun

    2013-04-30

    Poly(amidoamine) (PAMAM) encapsulated platinum nanoparticles were synthesized and used as catalase mimics. Acetylated generation 9 (Ac-G9) PAMAM dendrimer with a molecular size around 10 nm was used as a template to synthesize platinum nanoparticles. The feeding molar ratio of Pt(4+) and Ac-G9 is 2048, and the synthesized platinum nanoparticle (Ac-G9/Pt NP) has an average size of 3.3 nm. Ac-G9/Pt NP has a similar molecular size and globular shape with catalase (~11 nm). The catalytic activity of Ac-G9/Pt NP on the decomposition of H2O2 is approaching that of catalase at 37 °C. Ac-G9/Pt NP shows differential response to the changes of pH and temperature compared with catalase, which can be explained by different catalytic mechanisms of Ac-G9/Pt NP and catalase. Ac-G9/Pt NP also shows horseradish peroxidase activity and is able to scavenge free radicals such as di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium (DPPH). Furthermore, Ac-G9/Pt NP shows excellent biocompatibility on different cell lines and can down-regulate H2O2-induced intracellular reactive oxygen species (ROS) in these cells. These results suggest that dendrimers are promising mimics of proteins with different sizes and Ac-G9/Pt NP can be used as an alternative candidate of catalase to decrease oxidation stress in cells.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2015-08-15

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

  8. 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

  9. Characterization of and biomolecule immobilization on the biocompatible multi-walled carbon nanotubes generated by functionalization with polyamidoamine dendrimers.

    Science.gov (United States)

    Zhang, Baoling; Chen, Qiong; Tang, Hao; Xie, Qingji; Ma, Ming; Tan, Liang; Zhang, Youyu; Yao, Shouzhuo

    2010-10-01

    Polyamidoamine (PAMAM) dendrimers were covalently tethered onto the surface of multi-walled carbon nanotubes (MWCNTs). The morphology and dispersive properties of the MWCNT-PAMAM hybrids were characterized and the peripheral functional groups were identified. Cytotoxicity to human osteosarcoma MG-63 cells, and protein and DNA immobilization ability of the hybrids were evaluated in detail. The dendrimers were present on the surface of MWCNTs in high density. The MWCNT-PAMAM hybrids exhibited good dispersibility and stability in aqueous solution. We showed that the hybrids are biocompatible, with no obvious cytotoxicity at concentration biomolecule-immobilization ability (bovine serum albumin and 5'-Fam-CAAggTCgTgTAAAggTCAg-3' were used as models). The functionalization of MWCNTs with PAMAM dendrimers improved the biomolecule-immobilization ability 70-fold and simultaneously decreased the cellular toxicity by about 30%. It is expected that the MWCNT-PAMAM hybrids will find promising applications in biosensors and biomolecule delivery systems in gene or protein therapy.

  10. Poly(amidoamine) dendrimers show carbonic anhydrase inhibitory activity against α-, β-, γ- and η-class enzymes.

    Science.gov (United States)

    Carta, Fabrizio; Osman, Sameh M; Vullo, Daniela; AlOthman, Zeid; Del Prete, Sonia; Capasso, Clemente; Supuran, Claudiu T

    2015-11-01

    Four generations of poly(amidoamine) (PAMAM) dendrimers incorporating benzenesulfonamide moieties were investigated as inhibitors of carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the α-, β-, γ- and η-classes which are present in pathogenic bacteria, fungi or protozoa. The following bacterial, fungal and protozoan organisms were included in the study: Vibrio cholerae, Trypanosoma cruzi, Leishmania donovani chagasi, Porphyromonas gingivalis, Cryptococcus neoformans, Candida glabrata, and Plasmodium falciparum. The eight pathozymes present in these organisms were efficiently inhibited by the four generations PAMAM-sulfonamide dendrimers, but multivalency effects were highly variable among the different enzyme classes. The Vibrio enzyme VchCA was best inhibited by the G3 dendrimer incorporating 32 sulfamoyl moieties. The Trypanosoma enzyme TcCA on the other hand was best inhibited by the first generation dendrimer G0 (with 4 sulfamoyl groups), whereas for other enzymes the optimal inhibitory power was observed for the G1 or G2 dendrimers, with 8 and 16 sulfonamide functionalities. This study thus proves that the multivalency may be highly relevant for enzyme inhibition for some but not all CAs from pathogenic organisms. On the other hand, some dendrimers investigated here showed a better inhibitory power compared to acetazolamide for enzymes from widespread pathogens, such as the η-CA from Plasmodium falciparum. Overall, the main conclusion is that this class of molecules may lead to important developments in the field of anti-infective CA inhibitors.

  11. Polyamidoamine dendrimer-based binders for high-loading lithium–sulfur battery cathodes

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharya, Priyanka; Nandasiri, Manjula I.; Lv, Dongping; Schwarz, Ashleigh M.; Darsell, Jens T.; Henderson, Wesley A.; Tomalia, Donald A.; Liu, Jun; Zhang, Ji-Guang; Xiao, Jie

    2016-01-01

    Lithium-sulfur (Li-S) batteries are regarded as one of the most promising candidates for next generation energy storage systems because of their ultra high theoretical specific energy. To realize the practical application of Li-S batteries, however, a high S active material loading is essential (>70 wt% in the carbon-sulfur (C-S) composite cathode and >2 mg cm-2 in the electrode). A critical challenge to achieving this high capacity in practical electrodes is the dissolution of the longer lithium polysulfide reaction intermediates in the electrolyte (resulting in loss of active material from the cathode and contamination of the anode due to the polysulfide shuttle mechanism). The binder material used for the cathode is therefore crucial as this is a key determinant of the bonding interactions between the active material (S) and electronic conducting support (C), as well as the maintenance of intimate contact between the electrode materials and current collector. The battery performance can thus be directly correlated with the choice of binder, but this has received only minimal attention in the relevant Li-S battery published literature. Here, we investigated the application of polyamidoamine (PAMAM) dendrimers as functional binders in Li-S batteries—a class of materials which has been unexplored for electrode design. By using dendrimers, it is demonstrated that high S loadings (>4 mg cm-2) can be easily achieved using "standard" (not specifically tailored) materials and simple processing methods. An exceptional electrochemical cycling performance was obtained (as compared to cathodes with conventional linear polymeric binders such as carboxymethyl cellulose (CMC) and styrene-butadiene rubber (SBR)) with >100 cycles and 85-98% capacity retention, thus demonstrating the significant utility of this new binder architecture which exhibits critical physicochemical properties and flexible nanoscale design parameters (CNDP's).

  12. Adsorption of Pb(II) from aqueous solution by silica-gel supported hyperbranched polyamidoamine dendrimers.

    Science.gov (United States)

    Niu, Yuzhong; Qu, Rongjun; Sun, Changmei; Wang, Chunhua; Chen, Hou; Ji, Chunnuan; Zhang, Ying; Shao, Xia; Bu, Fanling

    2013-01-15

    The adsorption properties of silica-gel supported hyperbranched polyamidoamine dendrimers (SiO(2)-G0-SiO(2)-G4.0) have been investigated by batch method. The effect of pH of the solution, contact time, initial Pb(II) ion concentration, temperature and coexisting metal ions have been demonstrated. The results indicated that the optimum pH value was 5. Adsorption kinetics was found to follow the pseudo-second-order model and controlled by film diffusion. The adsorption isotherms were fitted by Langmuir, Freundlich and Dubinin-Radushkevich (D-R) isotherm models. Langmuir isotherm model was found to be more suitable to describe the equilibrium data, suggesting the uptake of Pb(II) ions by monolayer adsorption. From D-R isotherm model, the calculated mean free energy E demonstrated the adsorption processes occurred by chemical ion-exchange mechanism. FTIR analysis revealed that amine groups were mainly responsible for the adsorption of Pb(II) by amino-terminated adsorbents, while CO of ester groups also participated in the adsorption process of ester-terminated ones. The adsorbents can selectively adsorb Pb(II) from binary ion systems in the presence of Mn(II), Cu(II), Co(II), and Ni(II). Based on the results, it is concluded that SiO(2)-G0-SiO(2)-G4.0 had great potential for the removal of Pb(II) from aqueous solution.

  13. Preparation and properties of novel hydrogel based on chitosan modified by poly(amidoamine) dendrimer.

    Science.gov (United States)

    He, Guanghua; Zhu, Chao; Ye, Shengyang; Cai, Weiquan; Yin, Yihua; Zheng, Hua; Yi, Ying

    2016-10-01

    Currently, chitosan (CTS) or chitosan derivatives hydrogels are applied in different fields, such as biological materials, medical materials and hygiene materials. In this study, novel chitosan hydrogels were successfully prepared by chitosan and poly(amidoamine) (PAMAM) dendrimer with glutaraldehyde serving as a cross-linking agent. Fourier transform infrared spectroscopy (FTIR), (1)H nuclear magnetic resonance ((1)H NMR) and gel permeation chromatography (GPC) were performed to characterize PAMAM. The structure and morphology of hydrogels were characterized by FTIR, thermo gravimetry analysis (TGA), and scanning electron microscopy (SEM). The swelling properties of the hydrogels were investigated in solutions of pH 1.0 and 7.4. The hydrogels showed good swelling capacities and pH-sensitive swelling properties. Besides, the antibacterial activities of the hydrogels against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) were tested by optical density. Compared with the pure chitosan hydrogel, their antibacterial activities were significantly improved with the increase in the blending ratio of PAMAM. And with the increase in cross-linking agent and concentration of CTS, the antibacterial activities increased firstly and then slightly decreased. The hydrogel was expected to be a novel antibacterial material.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. Preparation and Biophysical Characterization of Poly(amidoamine) Dendrimer-Poly(acrylic acid) Graft.

    Science.gov (United States)

    Dung, Tran Huu; Do, Le Thanh; Loan, Ta Thi; Yoo, Hoon

    2015-01-01

    A series of PAMAM dendrimer generation 5-poly(acrylic acid) grafts were prepared to evaluate the potential use of dendritic grafts as a drug encapsulated nanocarrier. The structural features of the synthesized polymer graft were identified by FT-IR and 1H-NMR spectra and the biophysical properties were characterized by measuring its particle size and zeta potential. The prepared dendrimer G5-PAA grafts had particle size in the range of 600 to 900 nm and the size increased proportionally with the number of PAA on dendrimer surface. The electrostatic property of the dendrimer G5-PAA, carried out by HPLC reversed phase column analysis and the measurement of zeta potential, revealed that both migration time and zeta potential were dependent on the number of grafted PAA. The number of free amino groups on dendrimer G5-PAA, determined quantitatively by fluorescamine assay, was in a reverse order with the reaction mole ratio of dendrimer to PAA. In addition, dendrimer G5-PAA showed a pH-dependent solubility in aqueous solution with characteristic pH region of solubility, depending on the dendrimer generation. The observed biophysical properties indicate that PAMAM dendrimer G5-PAA is promising as a drug encapsulated nanocarrier.

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

    Science.gov (United States)

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

    2014-07-14

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

  20. Carbon nanotube filled with magnetic iron oxide and modified with polyamidoamine dendrimers for immobilizing lipase toward application in biodiesel production

    Science.gov (United States)

    Fan, Yanli; Su, Feng; Li, Kai; Ke, Caixia; Yan, Yunjun

    2017-01-01

    Superparamagnetic multi-walled carbon nanotubes (mMWCNTs) were prepared by filling multi-walled carbon nanotubes (MWCNTs) with iron oxide, and further modified by linking polyamidoamine (PAMAM) dendrimers (mMWCNTs-PAMAM) on the surface. Then, mMWCNTs-PAMAM was employed as the carrier and successfully immobilized Burkholderia cepacia lipase (BCL) via a covalent method (BCL-mMWCNTs-G3). The maximum activity recovery of the immobilized lipase was 1,716% and the specific activity increased to 77,460 U/g-protein, 17-fold higher than that of the free enzyme. The immobilized lipase displayed significantly enhanced thermostability and pH-resistance, and could efficiently catalyze transesterification to produce biodiesel at a conversion rate of 92.8%. Moreover, it possessed better recycling performance. After 20 cycles of repeated used, it still retained ca. 90% of its original activity, since the carbon nanotube−enzyme conjugates could be easily separated from the reaction mixture by using a magnet. This study provides a new perspective for biotechnological applications by adding a magnetic property to the unique intrinsic properties of nanotubes. PMID:28358395

  1. Direct electrochemistry of hemoglobin and biosensing for hydrogen peroxide using a film containing silver nanoparticles and poly(amidoamine) dendrimer

    Energy Technology Data Exchange (ETDEWEB)

    Baccarin, Marina [Nanomedicine and Nanotoxicology Group, Instituto de Física de São Carlos, Universidade de São Paulo, 13566-390 São Carlos, SP (Brazil); Departamento de Química, Universidade Federal de São Carlos, 13565-970 São Carlos, SP (Brazil); Janegitz, Bruno C., E-mail: brunocj@ymail.com [Departamento de Química, Universidade Federal de São Carlos, 13565-970 São Carlos, SP (Brazil); Departamento de Ciências da Natureza, Matemática e Educação, Universidade Federal de São Carlos, 13600-970 Araras, SP (Brazil); Berté, Rodrigo [Nanomedicine and Nanotoxicology Group, Instituto de Física de São Carlos, Universidade de São Paulo, 13566-390 São Carlos, SP (Brazil); Vicentini, Fernando Campanhã [Departamento de Química, Universidade Federal de São Carlos, 13565-970 São Carlos, SP (Brazil); Banks, Craig E. [Faculty of Science and Engineering, School of Chemistry and the Environment, Division of Chemistry and Environmental Science, Manchester Metropolitan University, Chester Street, Manchester M15GD (United Kingdom); Fatibello-Filho, Orlando [Departamento de Química, Universidade Federal de São Carlos, 13565-970 São Carlos, SP (Brazil); and others

    2016-01-01

    A new architecture for a biosensor is proposed using a glassy carbon electrode (GCE) modified with hemoglobin (Hb) and silver nanoparticles (AgNPs) encapsulated in poly(amidoamine) dendrimer (PAMAM). The biosensors were characterized using ultraviolet–visible spectroscopy, ζ-potential and cyclic voltammetry to investigate the interactions between Hb, AgNPs and the PAMAM film. The biosensor exhibited a well-defined cathodic peak attributed to reduction of the Fe{sup 3+} present in the heme group in Hb, as revealed by cyclic voltammetry in the presence of O{sub 2}. An apparent heterogeneous electron transfer rate of 4.1 s{sup −1} was obtained. The Hb–AgNPs-PAMAM/GCE third generation biosensor was applied in the amperometric determination of hydrogen peroxide over the linear range from 6.0 × 10{sup −6} to 9.1 × 10{sup −5} mol L{sup −1} with a detection limit of 4.9 × 10{sup −6} mol L{sup −1}. The proposed method can be extended to immobilize and evaluate the direct electron transfer of other redox enzymes. - Highlights: • A new architecture for biosensor using Hb, AgNPs and PAMAM is proposed. • H{sub 2}O{sub 2} is determined by amperometry using the proposed third generation biosensor. • The direct electron transfer was obtained from Hb using Hb–AgNPs–PAMAM.

  2. 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

    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.

  3. Poly(amidoamine) dendrimer nanocarriers and their aerosol formulations for siRNA delivery to the lung epithelium.

    Science.gov (United States)

    Conti, Denise S; Brewer, Daniel; Grashik, Jordan; Avasarala, Sumant; da Rocha, Sandro R P

    2014-06-02

    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 siRNA has

  4. Functionalization of poly(amidoamine) dendrimer-based nano-architectures using a naphthalimide derivative and their fluorescent, dyeing and antimicrobial properties on wool fibers.

    Science.gov (United States)

    Sadeghi-Kiakhani, Mousa; Safapour, Siyamak

    2016-06-01

    Novel naphthalimide-poly(amidoamine) dendrimer fluorescent dyes were synthesized, and their structures were identified and confirmed using different characterization methods such as Fourier transform infrared, (1) H NMR, (13) C NMR, differential scanning calorimetry, elemental analysis and UV-vis spectroscopy. The spectrophotometric studies demonstrated absorption maxima (λmax ) and extinction coefficient (εmax ) values in the ranges of 429-438 nm and 25,635-88,618 L/mol/cm, respectively. The dyeing, fastness and antimicrobial properties of dyed wool fibers were examined. Colorimetric measurements demonstrated a greenish-yellow hue with remarkable fluorescence intensity on dyed wool. Although the fastness properties of naphthalimide dye on wool fibers were poor/moderate, color fastness was appreciably improved through modification of the dye using dendrimers. The results revealed that the newly synthesized dyes are potent antimicrobial agents on wool fibers. Overall, it was deduced that poly(amidoamine) (PAMAM) dendrimers could be exploited as a promising tool in tailoring the different properties of naphthalimide dyes, being suitable for dyeing and antimicrobial finishing agents for wool fibers. Copyright © 2015 John Wiley & Sons, Ltd.

  5. 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

  6. 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.

  7. Enhanced Bioactivity of Internally Functionalized Cationic Dendrimers with PEG Cores

    Science.gov (United States)

    2012-11-09

    precipitation or dialysis as the only means of purification , greatly simplifying the synthetic process. Dendrimer−Cell Interactions. Previous studies...synthesis of dendrimers is still considered to be a time-consuming process requiring rigorous purification processes.14 Furthermore, partial...for the divergent synthesis of dendrimers.16−18 These strategies rely on the solubility of the PEG core to simplify purification of the PEG-dendrimer

  8. 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

    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...... caused by interactions between the positive charge centered at the core and the neighboring ester or amide dipoles. The relative ease of oxidation of TMePD and the lowest members of the series of the dendrimers can be reproduced theoretically only when solvation was included in the calculations. The DPV...

  9. 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

  10. 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.

  11. Syntheses, characterization and adsorption properties for Pb{sup 2+} of silica-gel functionalized by dendrimer-like polyamidoamine and 5-sulfosalicylic acid

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Xiongzhi, E-mail: 2004046@glut.edu.cn; Luo, Liangliang; Chen, Ziyan; Liang, Kailing

    2016-02-28

    Graphical abstract: SEM images of APSG, PAMAM-1.0SSASG, PAMAM-2.0SSASG, PAMAM-3.0SSASG and PAMAM-4.0SSASG. - Highlights: • Silica-gel adsorbents PAMAM-n.0SSASG (n = 1–4) with dendrimer-like polyamidoamine and 5-sulfosalicylic acid as functional groups were prepared. • The generation increase of grafted PAMAM changed the pore diameter distribution of adsorbent and adsorption/desorption property of PAMAM-4.0SSASG for Pb{sup 2+} was the best of four adsorbents. • The priority of adsorption property of PAMAM-4.0SSASG was explained by steric hindrance effect of PAMAM on adsorption/desorption, and selective adsorption of 5-sulfosalicylic acid with Pb{sup 2+}. • Pb{sup 2+} in standard reference sample and sea water sample were preconcentrated with PAMAM-4.0SSASG as adsorbent and determined by GFAAS. - Abstract: Silica-gel adsorbents PAMAM-n.0SSASG (n = 1–4) with dendrimer-like polyamidoamine (PAMAM) and 5-sulfosalicylic acid as functional groups were prepared and characterized with FTIR, SEM, TG, elemental analysis and porous structure analysis. Micro-column enrichment and measurement of Pb{sup 2+} with graphite furnace atomic absorption spectroscopy (GFAAS) was studied with PAMAM-n.0SSASG (n = 1–4) as adsorbent. It was emphasized to investigate the relationship between dynamic adsorption/desorption rates, adsorption capacities, and grafting percentage of PAMAM onto silica-gel surface. Experiments showed that the generation increase of grafted PAMAM changed the pore diameter distribution of adsorbent and obviously improved adsorption/desorption property for Pb{sup 2+}. Adsorption capacity of PAMAM-n.0SSASG (n = 1–4) was 14.04, 17.43, 20.07 and 25.05 mg g{sup −1} for Pb{sup 2+} respectively. An enrichment factor of 200 was obtained with PAMAM-4.0SSASG as adsorbent and with 2000 mL Pb{sup 2+} solution (1.0 ng mL{sup −1}). The priority of adsorption property of PAMAM-4.0SSASG was explained by steric hindrance effect of PAMAM on adsorption/desorption, and

  12. Synthesis of a novel polyamidoamine dendrimer conjugating with alkali blue as a lymphatic tracer and study on the lymphatic targeting in vivo.

    Science.gov (United States)

    Yang, Rui; Xia, Suxia; Ye, Tiantian; Yao, Jianhua; Zhang, Ruizhi; Wang, Shujun; Wang, Siling

    2016-09-01

    In this study, a novel lymphatic tracer polyamidoamin-alkali blue (PAMAM-AB) was synthesized in order to evaluate the intra-lymphatic targeting ability and lymphatic tropism of PAMAM-AB after subcutaneous administration. UV-Vis, FT-IR, NMR and HPLC characterization were performed to prove the successful synthesis of PAMAM-AB. The calculated AB payload of PAMAM-AB conjugate was seven per dendrimer molecule (27.16% by weight). Hydrolysis stability of PAMAM-AB in vitro was evaluated, which was stable in PBS and human plasma. Lymphatic tracing were studied to determine the blue-stained intensity of PAMAM-AB in right popliteral lymph nodes (PLNs), iliac lymph nodes (ILNs) and para-aortic lymph nodes (PALNs) after subcutaneous administration. The pharmacokinetics and biodistribution of PAMAM-AB in mice were investigated. PLNs, ILNs and PALNs could be obviously blue-stained within 10 min after PAMAM-AB administration, and displayed a more rapid lymphatic absorption, a higher AUC value in lymph nodes and a longer lymph nodes residence time compared with methylene blue solution (MB-S), MB water-in-oil microemulsion (MB-ME), MB multiple microemulsion (MB-MME). Enhanced lymphatic drainage from the injection site and uptake into lymph of PAMAM-AB indicated that PAMAM-AB possesses the double function of lymphatic tracing and lymphatic targeting, and suggested the potential for the development of lymphatic targeting vectors or as a lymphatic tracer in its own right.

  13. 聚酰胺-胺树状大分子的研究进展%Advancement of Research on Polyamidoamine Dendrimers

    Institute of Scientific and Technical Information of China (English)

    许晶

    2012-01-01

    聚酰胺-胺(PAMAM)是1985年由美国人Tomalia合成的一种树状大分子,现已广泛应用于基因载体、光电传感、废水处理、药物载体、催化剂等领域.本文综述了PAMAM树状大分子的结构和合成方法、细胞毒性,作为基因载体、药物载体所取得的成果以及PAMAM聚合物作为载体在胶质瘤治疗方面的研究进展及展望,并对今后胶质瘤放射治疗的研究方向进行了概述.%Polyamidoamine (PAMAM) dendrimers is synthesized by the American scientist, Tomalia, in 1985 and is now used widely in many fields such as gene carriers, photoelectric sensor, wastewater treatment, drug carriers and catalyst. The present paper mainly reviews the structure and methods of synthesis, celluar cytotoxeity, achievements of gene and drug carriers research, advancement and prospect of PAMAM as a carrier in glioma therapy. Besides, it also involves an outline for the future research of the radiotherapy for glioma.

  14. Nanogold-penetrated poly(amidoamine) dendrimer for enzyme-free electrochemical immunoassay of cardiac biomarker using cathodic stripping voltammetric method.

    Science.gov (United States)

    Zhang, Bo; Zhang, Yi; Liang, Wenbin; Cui, Bin; Li, Jiabei; Yu, Xuejun; Huang, Lan

    2016-01-21

    Methods based on immunoassays have been developed for cardiac biomarkers, but most involve the low sensitivity and are unsuitable for early disease diagnosis. Herein we design an electrochemical immunoassay for sensitive detection of myoglobin (a cardiac biomarker for acute myocardial infarction) by using nanogold-penetrated poly(amidoamine) dendrimer (AuNP-PAMAM) for signal amplification without the need of natural enzymes. The assay was carried out on the monoclonal mouse anti-myoglobin (capture) antibody-anchored glassy carbon electrode using polyclonal rabbit anti-myoglobin (detection) antibody-labeled AuNP-PAMAM as the signal tag. In the presence of target myoglobin, the sandwiched immunocomplex could be formed between capture antibody and detection antibody. Accompanying AuNP-PAMAM, the carried gold nanoparticles could be directly determined via stripping voltammetric method under acidic conditions. Under optimal conditions, the detectable electrochemical signal increased with the increasing target myoglobin in the sample within a dynamic working range from 0.01 to 500 ng mL(-1) with a detection limit of 3.8 pg mL(-1). The electrochemical immunoassay also exhibited high specificity and good precision toward target myoglobin. Importantly, our strategy could be applied for quantitative monitoring of myoglobin in human serum specimens, giving well matched results with those obtained from commercialized enzyme-linked immunosorbent assay (ELISA) method.

  15. Preparation of Layer-by-Layer Films Composed of Polysaccharides and Poly(Amidoamine Dendrimer Bearing Phenylboronic Acid and Their pH- and Sugar-Dependent Stability

    Directory of Open Access Journals (Sweden)

    Kentaro Yoshida

    2016-05-01

    Full Text Available Layer-by-layer films composed of polysaccharides and poly(amidoamine dendrimer bearing phenylboronic acid (PBA-PAMAM were prepared to study the deposition behavior of the films and their stability in buffer solutions and in sugar solutions. Alginic acid (AGA and carboxymethylcellulose (CMC were employed as counter-polymers in constructing LbL films. AGA/PBA-PAMAM films were successfully prepared at pH 6.0–9.0, whereas the preparation of CMC/PBA-PAMAM film was unsuccessful at pH 8.0 and 9.0. The results show that the LbL films formed mainly through electrostatic affinity between PBA-PAMAM and polysaccharides, while, for AGA/PBA-PAMAM films, the participation of boronate ester bonds in the films was suggested. AGA/PBA-PAMAM films were stable in the solutions of pH 6.0–9.0. In contrast, CMC/PBA-PAMAM films decomposed at pH 7.5–9.0. The AGA/PBA-PAMAM films decomposed in response to 5–30 mM fructose at pH 7.5, while the films were stable in glucose solutions. Thus, AGA is useful as a counter-polymer for constructing PBA-PAMAM films that are stable at physiological pH and decompose in response to fructose.

  16. 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.

  17. How do the full-generation poly(amido)amine (PAMAM) dendrimers activate blood platelets? Activation of circulating platelets and formation of "fibrinogen aggregates" in the presence of polycations.

    Science.gov (United States)

    Watala, Cezary; Karolczak, Kamil; Kassassir, Hassan; Talar, Marcin; Przygodzki, Tomasz; Maczynska, Katarzyna; Labieniec-Watala, Magdalena

    2016-04-30

    Direct use of poly(amido)amine (PAMAM) dendrimers as drugs may be limited, due to uncertain (cyto)toxicity. Peripheral blood components, which constitute the first line of a contact with administered pharmaceuticals, may become vastly affected by PAMAM dendrimers. The aim of this study was to explore how PAMAMs' polycationicity might affect blood platelet activation and reactivity, and thus trigger various haemostatic events. We monitored blood platelet reactivity in rats with experimental diabetes upon a long-term administration of the unmodified PAMAM dendrimers. In parallel, the effects on blood flow in a systemic circulation was recorded intravitally in mice administered with PAMAM G2, G3 or G4. Compounding was the in vitro approach to monitor the impact of PAMAM dendrimers on blood platelet activation and reactivity and on selected haemostatic and protein conformation parameters. We demonstrated the activating effects of polycations on blood platelets. Some diversity of the revealed outcomes considerably depended on the used approach and the particular technique employed to monitor blood platelet function. We discovered undesirable impact of plain PAMAM dendrimers on primary haemostasis and their prothrombotic influence. We emphasize the need of a more profound verifying of all the promising findings collected for PAMAMs with the use of well-designed in vivo preclinical studies.

  18. Ultrasonic synthesis and spectral characterization of a new blue fluorescent dendrimer as highly selective chemosensor for Fe3+ cations

    Science.gov (United States)

    Staneva, Desislava; Bosch, Paula; Grabchev, Ivo

    2012-05-01

    A poly(propyleneamine) dendrimer, comprising four 4-(N,N-dimethylaminoethyloxy)-1,8-naphthalimide units in the dendrimer periphery has been synthesized for the first time. The new blue fluorescent dendrimer has been obtained by nucleophilic substitution of the nitro groups at C-4 position of 1,8-naphthalimide units by N,N-dimethylaminoethyloxy moiety under ultrasonic conditions. Its photophysical characteristics have been investigated in organic solvents of different polarity. The influence of different metal cations on the dendrimer fluorescence has been also investigated viewing its sensor potential.

  19. Interaction of cationic carbosilane dendrimers and their complexes with siRNA with erythrocytes and red blood cell ghosts.

    Science.gov (United States)

    Wrobel, Dominika; Kolanowska, Katarzyna; Gajek, Arkadiusz; Gomez-Ramirez, Rafael; de la Mata, Javier; Pedziwiatr-Werbicka, Elżbieta; Klajnert, Barbara; Waczulikova, Iveta; Bryszewska, Maria

    2014-03-01

    We have investigated the interactions between cationic NN16 and BDBR0011 carbosilane dendrimers with red blood cells or their cell membranes. The carbosilane dendrimers used possess 16 cationic functional groups. Both the dendrimers are made of water-stable carbon-silicon bonds, but NN16 possesses some oxygen-silicon bonds that are unstable in water. The nucleic acid used in the experiments was targeted against GAG-1 gene from the human immunodeficiency virus, HIV-1. By binding to the outer leaflet of the membrane, carbosilane dendrimers decreased the fluidity of the hydrophilic part of the membrane but increased the fluidity of the hydrophobic interior. They induced hemolysis, but did not change the morphology of the cells. Increasing concentrations of dendrimers induced erythrocyte aggregation. Binding of short interfering ribonucleic acid (siRNA) to a dendrimer molecule decreased the availability of cationic groups and diminished their cytotoxicity. siRNA-dendrimer complexes changed neither the fluidity of biological membranes nor caused cell hemolysis. Addition of dendriplexes to red blood cell suspension induced echinocyte formation.

  20. IL-6 Antibody and RGD Peptide Conjugated Poly(amidoamine) Dendrimer for Targeted Drug Delivery of HeLa Cells.

    Science.gov (United States)

    Mekuria, Shewaye Lakew; Debele, Tilahun Ayane; Chou, Hsiao-Ying; Tsai, Hsieh-Chih

    2016-01-14

    In this study, PAMAM dendrimer (G4.5) was conjugated with two targeting moieties, IL-6 antibody and RGD peptide (G4.5-IL6 and G4.5-RGD conjugates). Doxorubicin anticancer drug was physically loaded onto G4.5-IL6 and G4.5-RGD with the encapsulation efficiency of 51.3 and 30.1% respectively. The cellular internalization and uptake efficiency of G4.5-IL6/DOX and G4.5-RGD/DOX complexes was observed and compared by confocal microscopy and flow cytometry using HeLa cells, respectively. The lower IC50 value of G4.5-IL6/DOX in comparison to G4.5-RGD/DOX is indication that higher drug loading and faster drug release rate corresponded with greater cytotoxicity. The cytotoxic effect was further verified by increment in late apoptotic/necrotic cells due to delivery of drug through receptor-mediated endocytosis. On the basis of these results, G4.5-IL6 is a better suited carrier for targeted drug delivery of DOX to cervical cancer cells.

  1. Propagation of structural deviations of poly(amidoamine) fan-shape dendrimers (generations 0-3) characterized by MALDI and electrospray mass spectrometry

    Science.gov (United States)

    Giordanengo, Rémi; Mazarin, Michaël; Wu, Jiangyu; Peng, Ling; Charles, Laurence

    2007-10-01

    Fan-shape PAMAM dendrimers, from generations 0 to 3, were analyzed by mass spectrometry, using both MALDI and electrospray ionization techniques, to identify any structural deviations present in each sample. First, it could be concluded that all detected molecules were present in the samples as they were detected in MALDI as well as in electrospray mass spectra. Apart from commonly reported dendrimer defects ("missing arm" and "molecular loop"), new impurities were found to arise from propagation of these defects during the synthesis of upper generations. These assignments were based on both compound molecular weight and, when ions were detected with sufficient abundance, deviations from perfect structure behaviour during MS/MS experiments. Since new impurities could be created, either from perfect or defective molecules, during each new generation dendrimer synthesis, models were built to predict the molecular weight of a compound as a function of its synthesis history and efficiently guide mass spectral interpretation.

  2. 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...

  3. 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

  4. Fluorescent hydroxylamine derived from the fragmentation of PAMAM dendrimers for intracellular hypochlorite recognition.

    Science.gov (United States)

    Wu, Te-Haw; Liu, Ching-Ping; Chien, Chih-Te; Lin, Shu-Yi

    2013-08-26

    Herein, a promising sensing approach based on the structure fragmentation of poly(amidoamine) (PAMAM) dendrimers for the selective detection of intracellular hypochlorite (OCl(-)) is reported. PAMAM dendrimers were easily disrupted by a cascade of oxidations in the tertiary amines of the dendritic core to produce an unsaturated hydroxylamine with blue fluorescence. Specially, the novel fluorophore was only sensitive to OCl(-), one of reactive oxygen species (ROS), resulting in an irreversible fluorescence turn-off. The fluorescent hydroxylamine was selectively oxidised by OCl(-) to form a labile oxoammonium cation that underwent further degradation. Without using any troublesomely synthetic steps, the novel sensing platform based on the fragmentation of PAMAM dendrimers, can be applied to detect OCl(-) in macrophage cells. The results suggest that the sensing approach may be useful for the detection of intracellular OCl(-) with minimal interference from biological matrixes.

  5. 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.

  6. 聚酰胺-胺型树枝状大分子及其衍生物在基因传递中的应用%Functionalized Polyamidoamine Dendrimer as Gene Delivery Vectors

    Institute of Scientific and Technical Information of China (English)

    董博; 闫熙博; 牛玉洁; 王欣; 王连永; 王燕铭

    2012-01-01

    Gene therapy has emerged as the most promising therapeutic strategy for various human diseases such as cardiovascular disorders, neurological disease, and cancers by introducing functional gene into body via gene vectors. For the successful advancement of gene therapy, the further development of safer and more efficient gene delivery vectors has been an advanced topic in the researches of bioactive materials and gene delivery. Recently, polyamidoamine (PAMAM) dendrimers have been intensively studied because of their well-defined three-dimensional structures, relatively lower toxicity, possibility of facile modification, and capacity of carrying large gene segments. However, the applications of such molecules in gene delivery have been restricted by the complicated synthetic procedures and the laborious purification steps, as well as its lower transfection efficiency than virus. It is noted that surface modification of PAMAM dendrimers with series of bioactive molecules should intensively improve the transfection efficiency and biorecognition capacity. In this paper, an overview is presented with a focus on the PAMAM derivatives design and synthesis to enhance the gene delivery both in vitro and in vivo. We hope it may provide helpful insights for the further development of safe and efficient non-viral vectors.%基因治疗通过基因载体将治病基因导入病患的特异细胞以治疗心血管、神经系统疾病和癌症等。寻找安全高效的非病毒基因载体一直是基因治疗以及生物材料领域中的前沿课题。聚酰胺-胺型(PAMAM)树枝状高分子作为一类三维的、结构高度有序的新型载体,由于具有安全性好、易于修饰、携带外源基因容量大等特点,已经引起了广泛的关注。但是另一方面,合成步骤相对繁琐、后期产物纯化困难以及转染效率相对较低等问题限制了这类载体的进一步发展。本文结合本课题组的研究情况,针对如何提

  7. 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.

  8. 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…

  9. Generation 3 PAMAM dendrimer TAMRA conjugates containing precise dye/dendrimer ratios

    Science.gov (United States)

    Manono, Janet; Dougherty, Casey A.; Jones, Kirsten; DeMuth, Joshua; Holl, Mark M. Banaszak; DiMaggio, Stassi

    2015-01-01

    The synthesis, isolation, and characterization of generation 3 poly(amidoamine) (G3 PAMAM) dendrimer containing precise ratios of 5-carboxytetramethylrhodamine succinimidyl ester (TAMRA) dye (n = 1–3) per polymer particle are reported. Stochastic conjugation of TAMRA dye to the dendrimer was followed by separation into precise dye-polymer ratios using rp-HPLC. The isolated materials were characterized by rp-UPLC, MALDI-TOF-MS, and 1H NMR spectroscopy, UV–vis, and fluorescence spectroscopies. PMID:26549978

  10. In vitro evaluation of the effectiveness of new water-stable cationic carbosilane dendrimers against Acanthamoeba castellanii UAH-T17c3 trophozoites.

    Science.gov (United States)

    Heredero-Bermejo, I; Copa-Patiño, J L; Soliveri, J; García-Gallego, S; Rasines, B; Gómez, R; de la Mata, F J; Pérez-Serrano, J

    2013-03-01

    Acanthamoeba is one of the most common free-living amoebas which is widespread in the environment and can infect humans, causing diseases such as keratitis and encephalitis. In this paper we examine for the first time the amebicidal activity of the family of cationic dendrimers nG-[Si{(CH(2))(3)N(+)(Me)(Et)(CH(2))(2)NMe(3) (+)}2I(-)]( x ) (where n denotes the generations: zero (n = 0, x = 1), first (n = 1, x = 4), and second (n = 2, x = 8); for simplicity, they were named as 0G-CNN2, 1G-CNN8, and 2G-CNN16, respectively) against Acanthamoeba castellanii UAH-T17c3 trophozoites. In order to test the amebicidal activity, we cultured the strain A. castellanii UAH-T17c3 in PYG-Bactocasitone medium and later, we treated it with different concentrations of these dendrimers and monitored the effects and damage by optical count, flow cytometry, and scanning electron microscopy. The results showed that all the nanosystems assayed had a strong amebicidal activity. The dendrimer 1G-CNN8 was the most effective against the amoeba. In the morphology of treated throphozoites of A. castellanii UAH-T17c3 analyzed by light and scanning electron microscopy techniques, morphological changes were evident in amoeba cells, such as loss of pseudopodia, ectoplasm increase, roundness, and cellular lysis. Furthermore, flow cytometry results showed alterations in cell granularity, which was dose-time dependent. In conclusion, this family of cationic carbosilane dendrimers has a strong amebicidal activity against the trophozoites of A. castellanii UAH-T17c3 in vitro. They could potentially become new agents significant to the development of new amebicidal compounds for prevention and therapy of Acanthamoeba infections.

  11. 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.

  12. 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.

  13. The cationic modification of hyperbranched polyamidoamine(PAMAM)and its flocculanting properties%超支化聚酰胺胺(PAMAM)的阳离子改性及絮凝性能

    Institute of Scientific and Technical Information of China (English)

    刘立新; 崔丽艳; 赵晓非; 吴得南; 马春曦; 郝松松

    2011-01-01

    Modified hyperbranched polyamidoamine(PAMAM) is used as a flocculant for waste water treatment,it was prepared by modification of its end groups with terminal cationic modified by using three kinds of cationic monomer in Michael addition. Impact of PAMAM modified reaction on the flocculation performance was analyzed with alkaline-surfactant-polymer (ASP)flooding fields simulated wastewater,and the modified structure of the product was characterized by IR. Experiment results showed that the preferred cationic monomer was methacryloyloxyethyl trimethyl ammonium chloride (DMC) ,the reaction was carried out at 660 ℃ for 36 h,m(DMC) ∶ m(PAMAM)=1. 2 ∶ 1,under the optimum condition,the flocculanting properties of the obtained product(PAMAM-DMC)was best.%采用3种阳离子单体,通过Michael加成反应,分别对超支化聚酰胺胺(PAMAM)进行了端基阳离子改性,改性产物作为絮凝剂用于处理油田污水.使用模拟三元复合驱油田污水,研究了PAM-AM改性反应条件对产物絮凝性能的影响,并对改性产物结构进行了红外表征.实验表明,优选阳离子单体甲基丙烯酰氧乙基三甲基氯化铵(DMC),反应温度60℃,时间36h,m(DMC):m(PAMAM)=1.2:1,在此条件下所得产物PAMAM-DMC的絮凝性能最佳.

  14. Transcorneal iontophoresis of dendrimers: PAMAM corneal penetration and dexamethasone delivery.

    Science.gov (United States)

    Souza, Joel G; Dias, Karina; Silva, Silas A M; de Rezende, Lucas C D; Rocha, Eduardo M; Emery, Flavio S; Lopez, Renata F V

    2015-02-28

    Iontophoresis of nanocarriers in the eye has been proposed to sustain drug delivery and maintain therapeutic concentrations. Fourth generation polyamidoamine (PAMAM) dendrimers are semi-rigid nanoparticles with surface groups that are easily modified. These dendrimers are known to modulate tight junctions, increase paracellular transport of small molecules and be translocated across epithelial barriers, exhibiting high uptake by different cell lines. The first aim of this study was to investigate the effect of iontophoresis on PAMAM penetration and distribution into the cornea. The second aim was to evaluate, ex vivo and in vivo, the effect of these dendrimers in dexamethasone (Dex) transcorneal iontophoresis. Anionic (PAMAM G3.5) and cationic (PAMAM G4) dendrimers were labeled with fluorescein isothiocyanate (FITC), and their distribution in the cornea was investigated using confocal microscopy after ex vivo anodal and cathodal iontophoresis for various application times. The particle size distribution and zeta potential of the dendrimers in an isosmotic solution were determined using dynamic light scattering and Nanoparticle Tracking Analysis (NTA), where the movement of small particles and the formation of large aggregates, from 5 to 100 nm, could be observed. Transcorneal iontophoresis increased the intensity and depth of PAMAM-FITC fluorescence in the cornea, suggesting improved transport of the dendrimers across the epithelium toward the stroma. PAMAM complexes with Dex were characterized by (13)C-NMR, (1)H-NMR and DOSY. PAMAM G3.5 and PAMAM G4 increased the aqueous solubility of Dex by 10.3 and 3.9-fold, respectively; however, the particle size distribution and zeta potential remained unchanged. PAMAM G3.5 decreased the Dex diffusion coefficient 48-fold compared with PAMAM G4. The ex vivo studies showed that iontophoresis increased the amount of Dex that penetrated into the cornea by 2.9, 5.6 and 3.0-fold for Dex, Dex-PAMAM G4 and Dex-PAMAM G3

  15. 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...

  16. 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.

  17. The influence of PAMAM dendrimers surface groups on their interaction with porcine pepsin.

    Science.gov (United States)

    Ciolkowski, Michal; Rozanek, Monika; Bryszewska, Maria; Klajnert, Barbara

    2013-10-01

    In this study the ability of three polyamidoamine (PAMAM) dendrimers with different surface charge (positive, neutral and negative) to interact with a negatively charged protein (porcine pepsin) was examined. It was shown that the dendrimer with a positively charged surface (G4 PAMAM-NH2), as well as the dendrimer with a neutral surface (G4 PAMAM-OH), were able to inhibit enzymatic activity of pepsin. It was also found that these dendrimers act as mixed partially non-competitive pepsin inhibitors. The negatively charged dendrimer (G3.5 PAMAM-COOH) was not able to inhibit the enzymatic activity of pepsin, probably due to the electrostatic repulsion between this dendrimer and the protein. No correlation between changes in enzymatic activity of pepsin and alterations in CD spectrum of the protein was observed. It indicates that the interactions between dendrimers and porcine pepsin are complex, multidirectional and not dependent only on disturbances of the secondary structure.

  18. Design, synthesis, characterization and drug release kinetics of PAMAM dendrimer based drug formulations

    Science.gov (United States)

    Kurtoglu, Yunus Emre

    The drug release characteristics of G4-polyamidoamine (PAMAM) dendrimer-ibuprofen conjugates with ester, amide, and peptide linkers were investigated, in addition to a linear PEG-ibuprofen conjugate to understand the effect of architecture and linker on drug release. Ibuprofen was directly conjugated to NH2 -terminated dendrimer by an amide bond and OH-terminated dendrimer by an ester bond. A tetra-peptide linked dendrimer conjugate and a linear mPEG-ibuprofen conjugate were also studied for comparison to direct linked dendrimer conjugates. It is demonstrated that the 3-D nanoscale architecture of PAMAM dendrimer-drug conjugates, along with linking chemistry govern the drug release mechanisms as well as kinetics. Understanding these structural effects on their drug release characteristics is crucial for design of dendrimer conjugates with high efficacy such as poly(amidoamine) dendrimer-N-Acetylcysteine conjugates with disulfide linkages. N-Acetylcysteine (NAC) is an anti-inflammatory agent with significant potential for clinical use in the treatment of neuroinflammation, stroke and cerebral palsy. A poly(amidoamine) dendrimer-NAC conjugate that contains a disulfide linkage was synthesized and evaluated for its release kinetics in the presence of glutathione (GSH), Cysteine (Cys), and bovine serum albumin (BSA) at both physiological and lysosomal pH. FITC-labeled conjugates showed that they enter cells rapidly and localize in the cytoplasm of lipopolysaccharide (LPS)-activated microglial cells. The efficacy of the dendrimer-NAC conjugate was measured in activated microglial cells using reactive oxygen species (ROS) assays. The conjugates showed an order of magnitude increase in anti-oxidant activity compared to free drug. When combined with intrinsic and ligand-based targeting with dendrimers, these types of GSH sensitive nanodevices can lead to improved drug release profiles and in vivo efficacy.

  19. 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.

  20. Evidence of guest encapsulation within G8 and G10 dendrimers using NMR techniques.

    Science.gov (United States)

    Shao, Naimin; Dai, Tianjiao; Liu, Yan; Li, Lei; Cheng, Yiyun

    2014-12-07

    Encapsulation of guest molecules within the interior cavities of dendrimers is promising, but high generation dendrimers show limited encapsulation capacity due to their dense surface shell. Here, for the first time, we prove that high generation polyamidoamine dendrimers, such as generation 8 and generation 10, are able to encapsulate hydrophobic guests using NMR spectroscopy. Guest molecules such as phenylbutazone, dexamethasone sodium phosphate and 9-anthracenecarboxylic acid with molecular weights up to 516 Da are in close proximity to the interior scaffold protons of high generation dendrimers. This encapsulation behavior depends on guest hydrophobicity. Chemical defects and back-folding of terminal groups make it possible for these guest molecules to penetrate through the dense surface shell of high generation dendrimers. These results provide new insights into the host-guest chemistry of dendrimers.

  1. 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.

  2. 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)

  3. 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.

  4. Electron Transfer in Methylene-Blue-Labeled G3 Dendrimers Tethered to Gold

    DEFF Research Database (Denmark)

    Álvarez-Martos, Isabel; Kartashov, Andrey; Ferapontova, Elena

    2016-01-01

    Redox-modified branched 3D dendrimeric nanostructures are considered a proper tool for the wiring of redox enzymes be-cause they provide both an enzyme-friendly environment and exquisite electron transfer (ET) mediation. ET rates in G3 poly-(amido)amine (PAMAM) dendrimers, covalently attached......,the ET mechanism switched from surface-confined ET (electron tunneling) in dilute monolayers to diffusional ET (electron hopping) at higher surface populations of dendrimers. Structural changes in the positively charged dendrimers electrostatically compressed at negative charges of the electrode surface...

  5. 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].

  6. 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.

  7. Lactose-Functionalized Dendrimers Arbitrate the Interaction of Galectin-3/MUC1 Mediated Cancer Cellular Aggregation

    Science.gov (United States)

    Michel, Anna K.; Nangia-Makker, Pratima; Raz, Avraham

    2015-01-01

    By using lactose-functionalized poly(amidoamine) dendrimers as a tunable multivalent platform, we studied cancer cell aggregation in three different cell lines (A549, DU-145, and HT-1080) with galectin-3. We found that small lactose-functionalized G(2)-dendrimer 1 inhibited galectin-3-induced aggregation of the cancer cells. In contrast, dendrimer 4 (a larger, generation 6 dendrimer with 100 carbohydrate end groups) caused cancer cells to aggregate through a galectin-3 pathway. This study indicates that inhibition of cellular aggregation occurred because 1 provided competitive binding sites for galectin-3 (compared to its putative cancer cell ligand, TF-antigen on MUC1). Dendrimer 4, in contrast, provided an excess of ligands for galectin-3 binding; this caused crosslinking and aggregation of cells to be increased. PMID:25138772

  8. Quasi-elastic light scattering of platinum dendrimer-encapsulated nanoparticles.

    Science.gov (United States)

    Wales, Christina H; Berger, Jacob; Blass, Samuel; Crooks, Richard M; Asherie, Neer

    2011-04-05

    Platinum dendrimer-encapsulated nanoparticles (DENs) containing an average 147 atoms were prepared within sixth-generation, hydroxyl-terminated poly(amidoamine) dendrimers (G6-OH). The hydrodynamic radii (R(h)) of the dendrimer/nanoparticle composites (DNCs) were determined by quasi-elastic light scattering (QLS) at high (pH ∼10) and neutral pH for various salt concentrations and identities. At high pH, the size of the DNC (R(h) ∼4 nm) is close to that of the empty dendrimer. At neutral pH, the size of the DNC approximately doubles (R(h) ∼8 nm) whereas that of the empty dendrimer remains unchanged. Changes in ionic strength also alter the size of the DNCs. The increase in size of the DNC is likely due to electrostatic interactions involving the metal nanoparticle.

  9. Electrostatic theory of the assembly of PAMAM dendrimers and DNA.

    Science.gov (United States)

    Perico, Angelo

    2016-05-01

    The electrostatic interactions mediated by counterions between a cationic PAMAM dendrimer, modelized as a sphere of radius and cationic surface charge highly increasing with generation, and a DNA, modelized as an anionic elastic line, are analytically calculated in the framework of condensation theory. Under these interactions the DNA is wrapped around the sphere. For excess phosphates relative to dendrimer primary amines, the free energy of the DNA-dendrimer complex displays an absolute minimum when the complex is weakly negatively overcharged. This overcharging opposes gene delivery. For a highly positive dendrimer and a DNA fixed by experimental conditions to a number of phosphates less than the number of dendrimer primary amines, excess amine charges, the dendrimer may at the same time bind stably DNA and interact with negative cell membranes to activate cell transfection in fair agreement with molecular simulations and experiments.

  10. 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.

  11. 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.

  12. 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.

  13. MECHANICAL PROPERTIES OF BLENDS OF PAMAM DENDRIMERS WITH POLY(VINYL CHLORIDE) AND POLY(VINYL ACETATE)

    Science.gov (United States)

    Hybrid blends of poly(amidoamine) PAMAM dendrimers with two linear high polymers, poly(vinyl chloride), PVC, and poly(vinyl acetate), PVAc, are reported. The interaction between the blend components was studied using dynamic mechanical analysis, xenon nuclear magnetic resonacne ...

  14. 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.

  15. 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.

  16. Dendrimer nanofluids in the concentrated regime: from polymer melts to soft spheres.

    Science.gov (United States)

    Pilkington, Georgia A; Pedersen, Jan S; Briscoe, Wuge H

    2015-03-24

    Understanding dendrimer structures and their interactions in concentrated solutions is important to a wide range of applications, such as drug delivery and lubrication. However, controversy has persisted concerning whether, when confined to proximity, dendrimers would entangle as observed for polymer systems, or act as deformable spheres. Furthermore, how such behavior may be related to their size-dependent molecular architecture remains unclear. Using small-angle X-ray scattering (SAXS), the intermolecular interactions and structures in aqueous nanofluids containing three generations of carboxyl-terminated poly(amidoamine) (PAMAM) dendrimers (G0.5, Rg = 9.3 Å; G3.5, Rg = 22.6 Å; G5.5, Rg = 39.9 Å, where Rg is the radius of gyration) over a mass fraction range 0.005 ≤ x ≤ 0.316 have been studied. In the highly concentrated regime (x ≥ 0.157), we observe that the solution properties depend on the dendrimer generation. Our results suggest that the smaller G0.5 dendrimers form a highly entangled polymer melt, while the larger dendrimers, G3.5 and G5.5, form densely packed and ordered structures, in which the individual dendrimers exhibit some degree of mutual overlap or deformation. Our results demonstrate the tunability of interdendrimer interactions via their molecular architecture, which in turn may be harnessed to control and tailor the physical properties of dendrimer nanofluids.

  17. Pegylated dendrimer and its effect in fluorouracil loading and release for enhancing antitumor activity.

    Science.gov (United States)

    Ly, Tu Uyen; Tran, Ngoc Quyen; Hoang, Thi Kim Dung; Phan, Kim Ngoc; Truong, Hai Nhung; Nguyen, Cuu Khoa

    2013-02-01

    Dendrimer, a new class of hyper-branched polymer with predetermined molecular weight, is being received much attention in nano biomedical applications such as anticancer drug delivery, gene therapy, disease diagnosis and etc. In this study, polyamidoamine (PAMAM)-based dendrimer generation 3.0 (G 3.0) was synthesized and subsequently pegylated. Obtained results showed that pegylation degree of the dendrimer was around 31% for its external amine groups. TEM image of the pegylated dendrimer exhibited spherical shape and nano sizes ranging from 30 to 40 nm. The fluorouracil (5-FU)-loaded pegylated dendrimer showed a slow release profile of the drug. In vitro study, at the primary screening concentration of 100 microg/mL, the PAMAM dendrimer presented higher toxicity in MCF-7 cells as compared to its pegylated counterpart. Meanwhile, the (5-FU)-loaded pegylated dendrimer exhibited the antiproliferative activity against the cell line with the IC50 of 9.92 +/- 0.19 microg/mL. In vivo tumor xenograft study, we succeeded in generating MCF-7 cells-derived cancer tumors on mice that was well-confirmed by using flow cytometer assay. The 5-FU encapsulated pegylated dendrimer exhibited a significant decrement in volume of the tumors which was generated by MCF-7 cancer cells.

  18. Mechanism of PAMAM Dendrimers Internalization in Hippocampal Neurons.

    Science.gov (United States)

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

    2016-10-03

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

  19. Different patterns of nuclear and mitochondrial penetration by the G3 PAMAM dendrimer and its biotin–pyridoxal bioconjugate BC-PAMAM in normal and cancer cells in vitro

    Directory of Open Access Journals (Sweden)

    Uram Ł

    2015-09-01

    Full Text Available Łukasz Uram,1 Magdalena Szuster,1 Aleksandra Filipowicz,2 Krzysztof Gargasz,3 Stanisław Wołowiec,3 Elżbieta Wałajtys-Rode4 1Bioorganic Chemistry Laboratory, Faculty of Chemistry, Rzeszow University of Technology, 2Cosmetology Department, University of Information Technology and Management in Rzeszow, 3Institute of Nursery and Health Sciences, Faculty of Medicine, University of Rzeszow, Rzeszow, 4Department of Drug Technology and Biotechnology, Faculty of Chemistry, Warsaw University of Technology, Warsaw, Poland Abstract: 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

  20. 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.

  1. Dendrimers in drug research

    DEFF Research Database (Denmark)

    Boas, Ulrik; Heegaard, Peter M. H.

    2004-01-01

    Dendrimers are versatile, derivatisable, well-defined, compartmentalised chemical polymers with sizes and physicochemical properties resembling those of biomolecules e.g. proteins. The present critical review (citing 158 references) briefly describes dendrimer design, nomenclature and divergent/c...

  2. Interaction of nucleic acids with carbon nanotubes and dendrimers.

    Science.gov (United States)

    Nandy, Bidisha; Santosh, Mogurampelly; Maiti, Prabal K

    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.

  3. 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.

  4. 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.

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    Fatemeh Nabavizadeh

    2016-09-01

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

  7. 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.

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

    Science.gov (United States)

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

    2016-09-01

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

  9. Carbosilane and Carbosiloxane Dendrimers

    Directory of Open Access Journals (Sweden)

    Jang Hwan Hong

    2009-09-01

    Full Text Available This review focuses on novel carbosilane dendrimers containing branches with Si-C and Si-O-C bonds. Introduction of organic moieties into the dendrimers is performed by hydrosilation of carbon-carbon double/triple bonds. Versatile organic or organometallic moieties are introduced onto the peripheral regions of dendrimers by coupling and complexation reactions, which clearly demonstrates their potential for variation.

  10. 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

  11. Fourier transform infrared spectroscopy (FTIR) characterization of the interaction of anti-cancer photosensitizers with dendrimers.

    Science.gov (United States)

    Dabrzalska, Monika; Benseny-Cases, Nuria; Barnadas-Rodríguez, Ramon; Mignani, Serge; Zablocka, Maria; Majoral, Jean-Pierre; Bryszewska, Maria; Klajnert-Maculewicz, Barbara; Cladera, Josep

    2016-01-01

    The systemic or local administration of a photosensitizer for photodynamic therapy is highly limited by poor selectivity, rapid deactivation and long-lasting skin toxicity due to unfavorable biodistribution. Drug delivery systems based on nanocarriers may help specific and effective delivery of photosensitizers. In the present paper, the interaction of two photosensitizers, methylene blue and rose bengal, with phosphorous cationic and anionic dendrimers as potential nanocarriers, has been characterized. A novel method is presented based on the analysis of the infrared spectra of mixtures of photosensitizer and dendrimer. The capacity of dendrimers to bind the photosensitizers has been evaluated by obtaining the corresponding binding curves. It is shown that methylene blue interacts with both cationic and anionic dendrimers, whereas rose bengal only binds to the cationic ones. Dendrimers are shown to be potential nanocarriers for a specific delivery of both photosensitizers.

  12. 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...

  13. 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 ...... as challenging issues surrounding the future development of dendrimer-based medicines....

  14. Direct Synthesis and Morphological Characterization of Gold-Dendrimer Nanocomposites Prepared Using PAMAM Succinamic Acid Dendrimers: Preliminary Study of the Calcification Potential

    Directory of Open Access Journals (Sweden)

    E. Vasile

    2014-01-01

    Full Text Available Gold-dendrimer nanocomposites were obtained for the first time by a simple colloidal approach based on the use of polyamidoamine dendrimers with succinamic acid terminal groups and dodecanediamine core. Spherical and highly crystalline nanoparticles with dimensions between 3 nm and 60 nm, and size-polydispersity depending on the synthesis conditions, have been generated. The influence of the stoichiometric ratio and the structural and architectural features of the dendrimers on the properties of the nanocomposites has been described. The self-assembling behaviour of these materials produces gold-dendrimer nanostructured porous networks with variable density, porosity, and composition. The investigations of the reaction systems, by TEM, at two postsynthesis moments, allowed to preliminary establish the control over the properties of the nanocomposite products. Furthermore, this study allowed better understanding of the mechanism of nanocomposite generation. Impressively, in the early stages of the synthesis, the organization of gold inside the dendrimer molecules has been evidenced by micrographs. Growth and ripening mechanisms further lead to nanoparticles with typical characteristics. The potential of such nanocomposite particles to induce calcification when coating a polymer substrate was also investigated.

  15. 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.

  16. Fluorescent Dendrimer Nanoconjugates as Advanced Probes for Biological Imaging

    Science.gov (United States)

    Reilly, Daniel; Kim, Sung Hoon; Katzenellenbogen, John A.; Schroeder, Charles M.

    2014-03-01

    Recent advances in fluorescence microscopy have enabled improvements in spatial resolution for biological imaging. However, there is a strong need for development of advanced fluorescent probes to enable a molecular-scale understanding of biological events. In this work, we report the development of a new class of probes for fluorescence imaging based on dye-conjugated dendrimer nanoconjugates. We utilize molecular-scale dendritic scaffolds as fluorescent probes, thereby enabling conjugation of multiple dyes and linkers to the scaffold periphery. In particular, we use polyamidoamine dendrimers as molecular scaffolds, wherein dye conjugation can be varied over a wide range. Single molecule fluorescence imaging shows that dendrimer nanoconjugates are far brighter than single fluorophores, resulting in increased localization precision. In addition, we further developed a new set of remarkably photostable probes by conjugating photoprotective triplet state quenchers directly onto the dendritic scaffold. We observe large increases in the photobleaching times compared to single dyes and reduced transient dark states (blinking). Overall, we believe that these new probes will allow for single molecule imaging over long time scales, enabling new vistas in biological imaging.

  17. Dendrimer-based nanocarriers demonstrating a high efficiency for loading and releasing anticancer drugs against cancer cells in vitro and in vivo

    Science.gov (United States)

    Quyen Tran, Ngoc; Khoa Nguyen, Cuu; Phuong Nguyen, Thi

    2013-12-01

    Dendrimer, a new class of hyper-branched polymer with predetermined molecular weight and well-controlled size, has received much attention in nanobiomedical applications such as drug carrier, gene therapy, disease diagnosis, etc. In this study, pegylated polyamidoamine (PAMAM) dendrimer at generation 3.0 (G 3.0) and carboxylated PAMAM dendrimer G 2.5 were prepared for loading anticancer drugs. For loading cisplatin, carboxylated dendrimer could carry 26.64 wt/wt% of cisplatin. The nanocomplexes have size ranging from 10 to 30 nm in diameter. The drug nanocarrier showed activity against NCI-H460 lung cancer cell line with half maximal inhibitory (IC50) of 23.11 ± 2.08 μg ml-1. Pegylated PAMAM dendrimers (G 3.0) were synthesized below 40 nm in diameter for carrying 5-fluorouracil (5-FU). For 5-FU encapsulation, pegylated dendrimer showed a high drug-loading efficiency of the drug and a slow release profile of 5-FU. The drug nanocarrier system exhibited an antiproliferative activity against MCF-7 cells (breast cancer cell) with a half maximal inhibitory (IC50) of 9.92 ± 0.19 μg ml-1. In vivo tumor xenograft study showed that the 5-FU encapsulated pegylation of dendrimer exhibited a significant decrement in volume of tumor which was generated by MCF-7 cancer cells. These positive results from our studies could pave the ways for further research of drugs dendrimer nanocarriers toward cancer chemotherapy.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. Targeting of follicle stimulating hormone peptide-conjugated dendrimers to ovarian cancer cells

    Science.gov (United States)

    Modi, Dimple A.; Sunoqrot, Suhair; Bugno, Jason; Lantvit, Daniel D.; Hong, Seungpyo; Burdette, Joanna E.

    2014-02-01

    Ovarian cancer is the most lethal gynecological malignancy. Current treatment modalities include a combination of surgery and chemotherapy, which often lead to loss of fertility in premenopausal women and a myriad of systemic side effects. To address these issues, we have designed poly(amidoamine) (PAMAM) dendrimers to selectively target the follicle stimulating hormone receptor (FSHR), which is overexpressed by tumorigenic ovarian cancer cells but not by immature primordial follicles and other non-tumorigenic cells. Fluorescein-labeled generation 5 (G5) PAMAM dendrimers were conjugated with the binding peptide domain of FSH (FSH33) that has a high affinity to FSHR. The targeted dendrimers exhibited high receptor selectivity to FSHR-expressing OVCAR-3 cells, resulting in significant uptake and downregulation of an anti-apoptotic protein survivin, while showing minimal interactions with SKOV-3 cells that do not express FSHR. The selectivity of the FSH33-targeted dendrimers was further validated in 3D organ cultures of normal mouse ovaries. Immunostaining of the conjugates revealed their selective binding and uptake by ovarian surface epithelium (OSE) cells that express FSHR, while sparing the immature primordial follicles. In addition, an in vivo study monitoring tissue accumulation following a single intraperitoneal (i.p.) injection of the conjugates showed significantly higher accumulation of FSH33-targeted dendrimers in the ovary and oviduct compared to the non-targeted conjugates. These proof-of-concept findings highlight the potential of these FSH33-targeted dendrimers to serve as a delivery platform for anti-ovarian cancer drugs, while reducing their systemic side effects by preventing nonspecific uptake by the primordial follicles.Ovarian cancer is the most lethal gynecological malignancy. Current treatment modalities include a combination of surgery and chemotherapy, which often lead to loss of fertility in premenopausal women and a myriad of systemic side

  5. PAMAM dendrimer-coated iron oxide nanoparticles: synthesis and characterization of different generations

    Energy Technology Data Exchange (ETDEWEB)

    Khodadust, Rouhollah, E-mail: raoul.1357@gmail.com; Unsoy, Gozde [Middle East Technical University, Department of Biotechnology (Turkey); Yalc Latin-Small-Letter-Dotless-I n, Serap [Ahi Evran University, Department of Food Engineering (Turkey); Gunduz, Gungor [Middle East Technical University, Department of Chemical Engineering (Turkey); Gunduz, Ufuk, E-mail: ufukg@metu.edu.tr [Middle East Technical University, Department of Biotechnology (Turkey)

    2013-03-15

    This study focuses on the synthesis and characterization of different generations (G{sub 0}-G{sub 7}) of polyamidoamine (PAMAM) dendrimer-coated magnetic nanoparticles (DcMNPs). In this study, superparamagnetic iron oxide nanoparticles were synthesized by co-precipitation method. The synthesized nanoparticles were modified with aminopropyltrimethoxysilane for dendrimer coating. Aminosilane-modified MNPs were coated with PAMAM dendrimer. The characterization of synthesized nanoparticles was performed by X-ray diffraction, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), dynamic light scattering, and vibrating sample magnetometry (VSM) analyses. TEM images demonstrated that the DcMNPs have monodisperse size distribution with an average particle diameter of 16 {+-} 5 nm. DcMNPs were found to be superparamagnetic through VSM analysis. The synthesis, aminosilane modification, and dendrimer coating of iron oxide nanoparticles were validated by FTIR and XPS analyses. Cellular internalization of nanoparticles was studied by inverted light scattering microscopy, and cytotoxicity was determined by XTT analysis. Results demonstrated that the synthesized DcMNPs, with their functional groups, symmetry perfection, size distribution, improved magnetic properties, and nontoxic characteristics could be suitable nanocarriers for targeted cancer therapy upon loading with various anticancer agents.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. Phosphorus Dendrimers as Carriers of siRNA—Characterisation of Dendriplexes

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Majoral

    2013-04-01

    Full Text Available There are many types of dendrimers used as nanomolecules for gene delivery but there is still an ongoing search for ones that are able to effectively deliver drugs to cells. The possibility of gene silencing using siRNA gives hope for effective treatment of numerous diseases. The aim of this work was to investigate in vitro biophysical properties of dendriplexes formed by siRNA and cationic phosphorus dendrimers of 3rd and 4th generation. First, using the ethidium bromide intercalation method, it was examined whether dendrimers have an ability to form complexes with siRNA. Next, the characterisation of dendriplexes formed at different molar ratios was carried out using biophysical methods. The effects of zeta potential, size and changes of siRNA conformation on the complexation with dendrimers were examined. It was found that both phosphorus dendrimers interacted with siRNA. The zeta potential values of dendriplexes ranged from negative to positive and the hydrodynamic diameter depended on the number of dendrimer molecules in the complex. Furthermore, using circular dichroism spectroscopy it was found that cationic phosphorus dendrimers changed only slightly the shape of siRNA CD spectra, thus they did not induce significant changes in the nucleic acid secondary structure during complex formation.

  11. 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...

  12. 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.

  13. 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.

  14. 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...

  15. Evaluation of assemblies based on carbon materials modified with dendrimers containing platinum nanoparticles for PEM-fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Ledesma-Garcia, J.; Barbosa, R.; Chapman, T.W.; Arriaga, L.G.; Godinez, Luis A. [Centro de Investigacion y Desarrollo Tecnologico en Electroquimica, S.C. Parque Tecnologico Queretaro-Sanfandila, 76703 Pedro Escobedo, Qro. (Mexico)

    2009-02-15

    Polyamidoamine (PAMAM) dendrimer-encapsulated Pt nanoparticles (G4OHPt) are synthesized by chemical reduction and characterized by transmission electronic microscopy. An H{sub 2}-O{sub 2} fuel cell has been constructed with porous carbon electrodes modified with the dendrimer nanocomposites. Electrochemical and physical impregnation methods of electrocatalyst immobilization are compared. The modified surfaces are used as electrodes and gas-diffusion layers in the construction of three different membrane-electrode assemblies (MEAs). The MEAs have been tested in a single polymer-electrolyte membrane-fuel cell at 30 C and 20 psig. The fuel cell is, then characterized by electrochemical impedance spectroscopy and cyclic voltammetry, and its performance evaluated in terms of polarization curves and power profiles. The highest fuel cell performance is reached in the MEA constructed by physical impregnation method. The results are compared with a 32 cm{sup 2} prototype cell using commercial electrocatalyst operated at 80 C, obtaining encouraging results. (author)

  16. 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.

  17. Dendrimer-mediated synthesis of platinum nanoparticles: new insights from dialysis and atomic force microscopy measurements

    Science.gov (United States)

    Xie, Hong; Gu, Yunlong; Ploehn, Harry J.

    2005-07-01

    In this work, we use AFM measurements in conjunction with dialysis experiments to study the synthesis mechanism and physical state of dendrimer-stabilized platinum nanoparticles. For characterizing particle size distributions by high resolution transmission electron microscopy and AFM, sample preparation by drop evaporation presumably minimizes the risk of sample bias that might be found in spin coating or dip-and-rinse methods. However, residual synthesis by-products (mainly salts) must be removed from solutions of dendrimer-stabilized metal nanoparticles prior to AFM imaging. Purification by dialysis is effective for this purpose. We discovered, by UV-visible spectrophotometry and atomic absorption (AA) spectroscopy, that dialysis using 'regular' cellulose dialysis tubing (12 000 Da cut-off) used in all previous work leads to substantial losses of poly(amidoamine) (PAMAM) dendrimer (G4OH), PAMAM-Pt(+2) complex, and PAMAM-stabilized Pt nanoparticles. Use of benzoylated dialysis tubing (1200 Da cut-off) shows no losses of G4OH or G4OH-Pt mixtures. We use AFM to see whether selective filtration during dialysis introduces sampling bias in the measurement of particle size distributions. We compare results (UV-visible spectra, AA results, and AFM-based particle size distributions) for a sample of G4OH-Pt40 divided into two parts, one part dialysed with regular dialysis tubing and the other with benzoylated tubing. Exhaustive dialysis using benzoylated tubing may lead to the loss of colloidal Pt nanoparticles stabilized by adsorbed dendrimer, but not Pt nanoparticles encapsulated by the dendrimer. The comparisons also lead to new insights concerning the underlying synthesis mechanisms for PAMAM-stabilized Pt nanoparticles.

  18. 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

  19. Development and validation of a reversed-phase high-performance liquid chromatographic method for quantification of peptide dendrimers in human skin permeation experiments.

    Science.gov (United States)

    Mutalik, S; Hewavitharana, A K; Shaw, P N; Anissimov, Y G; Roberts, M S; Parekh, H S

    2009-11-01

    The aim of the present work was to develop and validate a simple RP-HPLC method with UV detection to quantify peptide dendrimers in skin permeation experiments. Six dendrimers of varying positive charges (4(+), 8(+) and 16(+)) containing either histidine or arginine as terminal aminoacids were prepared by solid phase peptide synthesis. Mobile phase containing 0.02% (v/v) heptafluorobutyric acid in 90% acetonitrile-water was capable of separating all dendrimers from interfering peaks of receptor fluid. For the calibration of each dendrimer, a different dendrimer from the same class was selected as the internal standard. The results of preliminary human skin permeation studies showed that the developed analytical method can be successfully used for the quantification of cationic poly(aminoacid)-based dendrimers in skin permeation experiments.

  20. RNA-Based TWIST1 Inhibition via Dendrimer Complex to Reduce Breast Cancer Cell Metastasis

    Directory of Open Access Journals (Sweden)

    James Finlay

    2015-01-01

    Full Text Available Breast cancer is the leading cause of cancer-related deaths among women in the United States, and survival rates are lower for patients with metastases and/or triple-negative breast cancer (TNBC; ER, PR, and Her2 negative. Understanding the mechanisms of cancer metastasis is therefore crucial to identify new therapeutic targets and develop novel treatments to improve patient outcomes. A potential target is the TWIST1 transcription factor, which is often overexpressed in aggressive breast cancers and is a master regulator of cellular migration through epithelial-mesenchymal transition (EMT. Here, we demonstrate an siRNA-based TWIST1 silencing approach with delivery using a modified poly(amidoamine (PAMAM dendrimer. Our results demonstrate that SUM1315 TNBC cells efficiently take up PAMAM-siRNA complexes, leading to significant knockdown of TWIST1 and EMT-related target genes. Knockdown lasts up to one week after transfection and leads to a reduction in migration and invasion, as determined by wound healing and transwell assays. Furthermore, we demonstrate that PAMAM dendrimers can deliver siRNA to xenograft orthotopic tumors and siRNA remains in the tumor for at least four hours after treatment. These results suggest that further development of dendrimer-based delivery of siRNA for TWIST1 silencing may lead to a valuable adjunctive therapy for patients with TNBC.

  1. Polymer nanoparticles with dendrimer-Ag shell and its application in catalysis

    Institute of Scientific and Technical Information of China (English)

    Gaofei Dang; Yan Shi; Zhifeng Fu; Wantai Yang

    2013-01-01

    Polymer nanoparticles with dendrimer-Ag shell were prepared and their application in catalytic reduction of 4-nitrophenol (4-NP) was investigated.Cross-linked polystyrene (PS) microspheres were prepared through dispersion copolymerization of styrene,acrylic acid and crosslinking monomer 1,2-divinylbenzene.PS microspheres with average size of 450 nm and narrow size distribution were used as support for the immobilization of dendrimer-Ag shell.The polyamidoamine (PAMAM) dendrimer shell was successively grafted onto the surface of PS microspheres through repetitive Michael addition reaction of methyl acrylate (MA) and amidation of the obtained esters with large excess of ethylenediamine (EDA).Silver nanoparticles were formed directly inside the PAMAM shell through reduction with NaBH4.The resulting PS@PAMAM-Ag nanoparticles were packed in a stainless steel column and used successfully for catalytic reduction of 4-NP.This technique for packing catalytic polymer particles in a column could improve the efficiency of using the metal catalyst and the tedious separation in catalytic reaction.

  2. Dendrimer-Functionalized Laponite Nanodisks as a Platform for Anticancer Drug Delivery

    Directory of Open Access Journals (Sweden)

    Rania Mustafa

    2015-10-01

    Full Text Available In this study, we synthesized dendrimer-functionalized laponite (LAP nanodisks for loading and delivery of anticancer drug doxorubicin (DOX. Firstly, LAP was modified with silane coupling agents and succinic anhydride to render abundant carboxyl groups on the surface of LAP. Then, poly(amidoamine (PAMAM dendrimer of generation 2 (G2 were conjugated to form LM-G2 nanodisks. Anticancer drug DOX was then loaded on the LM-G2 with an impressively high drug loading efficiency of 98.4% and could be released in a pH-sensitive and sustained manner. Moreover, cell viability assay results indicate that LM-G2/DOX complexes could more effectively inhibit the proliferation of KB cells (a human epithelial carcinoma cell line than free DOX at the same drug concentration. Flow cytometry analysis and confocal laser scanning microscope demonstrated that LM-G2/DOX could be uptaken by KB cells more effectively than free DOX. Considering the exceptional high drug loading efficiency and the abundant dendrimer amine groups on the surface that can be further modified, the developed LM-G2 nanodisks may hold a great promise to be used as a novel platform for anticancer drug delivery.

  3. Automatic extraction of nanoparticle properties using natural language processing: NanoSifter an application to acquire PAMAM dendrimer properties.

    Science.gov (United States)

    Jones, David E; Igo, Sean; Hurdle, John; Facelli, Julio C

    2014-01-01

    In this study, we demonstrate the use of natural language processing methods to extract, from nanomedicine literature, numeric values of biomedical property terms of poly(amidoamine) dendrimers. We have developed a method for extracting these values for properties taken from the NanoParticle Ontology, using the General Architecture for Text Engineering and a Nearly-New Information Extraction System. We also created a method for associating the identified numeric values with their corresponding dendrimer properties, called NanoSifter. We demonstrate that our system can correctly extract numeric values of dendrimer properties reported in the cancer treatment literature with high recall, precision, and f-measure. The micro-averaged recall was 0.99, precision was 0.84, and f-measure was 0.91. Similarly, the macro-averaged recall was 0.99, precision was 0.87, and f-measure was 0.92. To our knowledge, these results are the first application of text mining to extract and associate dendrimer property terms and their corresponding numeric values.

  4. 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

    2015-12-02

    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.

  5. 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

  6. 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.

  7. Selective cytotoxicity of PAMAM G5 core–PAMAM G2.5 shell tecto-dendrimers on melanoma cells

    Directory of Open Access Journals (Sweden)

    Schilrreff P

    2012-07-01

    Full Text Available Priscila Schilrreff,1 Cecilia Mundiña-Weilenmann,2 Eder Lilia Romero,1 Maria Jose Morilla11Programa de Nanomedicinas, Universidad Nacional de Quilmes, Buenos Aires, Argentina; 2Centro de Investigaciones Cardiovasculares, Universidad Nacional de La Plata, La Plata, ArgentinaBackground: The controlled introduction of covalent linkages between dendrimer building blocks leads to polymers of higher architectural order known as tecto-dendrimers. Because of the few simple steps involved in their synthesis, tecto-dendrimers could expand the portfolio of structures beyond commercial dendrimers, due to the absence of synthetic drawbacks (large number of reaction steps, excessive monomer loading, and lengthy chromatographic separations and structural constraints of high-generation dendrimers (reduction of good monodispersity and ideal dendritic construction due to de Gennes dense-packing phenomenon. However, the biomedical uses of tecto-dendrimers remain unexplored. In this work, after synthesizing saturated shell core–shell tecto-dendrimers using amine-terminated polyamidoamine (PAMAM generation 5 (G5 as core and carboxyl-terminated PAMAM G2.5 as shell (G5G2.5 tecto-dendrimers, we surveyed for the first time the main features of their interaction with epithelial cells.Methods: Structural characterization of G5G2.5 was performed by polyacrylamide gel electrophoresis, matrix-assisted laser desorption time-of-flight mass spectrometry, and microscopic techniques; their hydrodynamic size and Z-potential was also determined. Cellular uptake by human epidermal keratinocytes, colon adenocarcinoma, and epidermal melanoma (SK-Mel-28 cells was determined by flow cytometry. Cytotoxicity was determined by mitochondrial activity, lactate dehydrogenase release, glutathione depletion, and apoptosis/necrosis measurement.Results: The resultant 60%–67% saturated shell, 87,000-dalton G5G2.5 (mean molecular weight interacted with cells in a significantly different

  8. Bioresponsive poly(amidoamine)s designed for intracellular protein delivery

    NARCIS (Netherlands)

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

    2013-01-01

    Poly(amidoamine)s with bioreducible disulfide linkages in the main chain (SS-PAAs) and pH-responsive, negatively charged citraconate groups in the sidechain have been designed for effective intracellular delivery and release of proteins with a net positive charge at neutral pH. Using lysozyme as a c

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

    Science.gov (United States)

    Oddone, Natalia; Zambrana, Ana I.; Tassano, Marcos; Porcal, Williams; Cabral, Pablo; Benech, Juan C.

    2013-07-01

    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.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. Fluorous Mixture Synthesis of Asymmetric Dendrimers

    Science.gov (United States)

    Jiang, Zhong-Xing; Yu, Yihua Bruce

    2010-01-01

    A divergent fluorous mixture synthesis (FMS) of asymmetric fluorinated dendrimers has been developed. Four generations of fluorinated dendrimers with the same fluorinated moiety were prepared with high efficiency, yield and purity. Comparison of the physicochemical properties of these dendrimers provided valuable information for their application and future optimization. This strategy has not only provided a practical method for the synthesis and purification of dendrimers, but also established the possibility of utilizing the same fluorinated moiety for FMS. PMID:20170088

  15. 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.

  16. GPCR ligand-dendrimer (GLiDe) conjugates: future smart drugs?

    Science.gov (United States)

    Jacobson, Kenneth A

    2010-12-01

    Unlike nanocarriers that are intended to release their drug cargo at the site of action, biocompatibile polyamidoamine (PAMAM) conjugates are designed to act at cell surface G protein-coupled receptors (GPCRs) without drug release. These multivalent GPCR ligand-dendrimer (GLiDe) conjugates display qualitatively different pharmacological properties in comparison with monomeric drugs. They might be useful as novel tools to study GPCR homodimers and heterodimers as well as higher aggregates. The structure of the conjugate determines the profile of biological activity, receptor selectivity, and physical properties such as water solubility. Prosthetic groups for characterization and imaging of receptors can be introduced without loss of affinity. The feasibility of targeting multiple adenosine and P2Y receptors for synergistic effects has been shown. Testing in vivo will be needed to explore the effects on pharmacokinetics and tissue targeting.

  17. 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.

  18. Polyester Dendrimers: Smart Carriers for Drug Delivery

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    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.

  19. RGD peptide-modified dendrimer-entrapped gold nanoparticles enable highly efficient and specific gene delivery to stem cells.

    Science.gov (United States)

    Kong, Lingdan; Alves, Carla S; Hou, Wenxiu; Qiu, Jieru; Möhwald, Helmuth; Tomás, Helena; Shi, Xiangyang

    2015-03-04

    We report the use of arginine-glycine-aspartic (Arg-Gly-Asp, RGD) peptide-modified dendrimer-entrapped gold nanoparticles (Au DENPs) for highly efficient and specific gene delivery to stem cells. In this study, generation 5 poly(amidoamine) dendrimers modified with RGD via a poly(ethylene glycol) (PEG) spacer and with PEG monomethyl ether were used as templates to entrap gold nanoparticles (AuNPs). The native and the RGD-modified PEGylated dendrimers and the respective well characterized Au DENPs were used as vectors to transfect human mesenchymal stem cells (hMSCs) with plasmid DNA (pDNA) carrying both the enhanced green fluorescent protein and the luciferase (pEGFPLuc) reporter genes, as well as pDNA encoding the human bone morphogenetic protein-2 (hBMP-2) gene. We show that all vectors are capable of transfecting the hMSCs with both pDNAs. Gene transfection using pEGFPLuc was demonstrated by quantitative Luc activity assay and qualitative evaluation by fluorescence microscopy. For the transfection with hBMP-2, the gene delivery efficiency was evaluated by monitoring the hBMP-2 concentration and the level of osteogenic differentiation of the hMSCs via alkaline phosphatase activity, osteocalcin secretion, calcium deposition, and von Kossa staining assays. Our results reveal that the stem cell gene delivery efficiency is largely dependent on the composition and the surface functionality of the dendrimer-based vectors. The coexistence of RGD and AuNPs rendered the designed dendrimeric vector with specific stem cell binding ability likely via binding of integrin receptor on the cell surface and improved three-dimensional conformation of dendrimers, which is beneficial for highly efficient and specific stem cell gene delivery applications.

  20. Facile formation of dendrimer-stabilized gold nanoparticles modified with diatrizoic acid for enhanced computed tomography imaging applications.

    Science.gov (United States)

    Peng, Chen; Li, Kangan; Cao, Xueyan; Xiao, Tingting; Hou, Wenxiu; Zheng, Linfeng; Guo, Rui; Shen, Mingwu; Zhang, Guixiang; Shi, Xiangyang

    2012-11-07

    We report a facile approach to forming dendrimer-stabilized gold nanoparticles (Au DSNPs) through the use of amine-terminated fifth-generation poly(amidoamine) (PAMAM) dendrimers modified by diatrizoic acid (G5.NH(2)-DTA) as stabilizers for enhanced computed tomography (CT) imaging applications. In this study, by simply mixing G5.NH(2)-DTA dendrimers with gold salt in aqueous solution at room temperature, dendrimer-entrapped gold nanoparticles (Au DENPs) with a mean core size of 2.5 nm were able to be spontaneously formed. Followed by an acetylation reaction to neutralize the dendrimer remaining terminal amines, Au DSNPs with a mean size of 6 nm were formed. The formed DTA-containing [(Au(0))(50)-G5.NHAc-DTA] DSNPs were characterized via different techniques. We show that the Au DSNPs are colloid stable in aqueous solution under different pH and temperature conditions. In vitro hemolytic assay, cytotoxicity assay, flow cytometry analysis, and cell morphology observation reveal that the formed Au DSNPs have good hemocompatibility and are non-cytotoxic at a concentration up to 3.0 μM. X-ray absorption coefficient measurements show that the DTA-containing Au DSNPs have enhanced attenuation intensity, much higher than that of [(Au(0))(50)-G5.NHAc] DENPs without DTA or Omnipaque at the same molar concentration of the active element (Au or iodine). The formed DTA-containing Au DSNPs can be used for CT imaging of cancer cells in vitro as well as for blood pool CT imaging of mice in vivo with significantly improved signal enhancement. With the two radiodense elements of Au and iodine incorporated within one particle, the formed DTA-containing Au DSNPs may be applicable for CT imaging of various biological systems with enhanced X-ray attenuation property and detection sensitivity.

  1. The specific contribution of phosphorus in dendrimer chemistry.

    Science.gov (United States)

    Majoral, Jean-Pierre; Caminade, Anne-Marie; Maraval, Valérie

    2002-12-21

    Besides properties commonly found for all types of dendrimers, phosphorus-containing dendrimers possess some specific properties seldom or never found for other types of dendrimers. Emphasis will be put on these specificities.

  2. Evaluation of Jeffamine®-cored PAMAM dendrimers as an efficient in vitro gene delivery system.

    Science.gov (United States)

    Aydin, Zeynep; Akbas, Fahri; Senel, Mehmet; Koc, S Naci

    2012-10-01

    In this study, we investigated gene delivery properties of Jeffamine-cored polyamidoamine (PAMAM) dendrimers (JCPDs). The effects of dendrimer concentration, generation, and core size on the gene delivery have been analyzed. The experimental results showed that the JCPD effectively delivered plasmid DNA inside the HeLa cells, and the transfection efficiency improved considerably as the number of generation increased. The cytotoxicity of JCPD in different concentration was tested for HeLa cell line. JCPD was complexed with a lacZ gene carrying plasmid and tested for transfection efficiency using quantitative β-galactosidase expression assay. Additionally, confocal microscopy results revealed that JCPD effectively delivered green fluorescent protein-expressing plasmid into HeLa cells and produced fluorescent signal with satisfactory efficiency. The highest transfection efficiency was obtained from JCPDs G4 and G5, which mixed with expression plasmid vectors at a 10/1 weight ratio. These results indicated that under optimized conditions, JCPD can be considered as an efficient transfection reagent and can be effectively used for gene delivery applications.

  3. 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

  4. PEGylated Dendrimers as Drug Delivery Vehicles for the Photosensitizer Silicon Phthalocyanine Pc 4 for Candidal Infections.

    Science.gov (United States)

    Hutnick, Melanie A; Ahsanuddin, Sayeeda; Guan, Linna; Lam, Minh; Baron, Elma D; Pokorski, Jonathan K

    2017-02-13

    Fungi account for billions of infections worldwide. The second most prominent causative agent for fungal infections is Candida albicans (C. albicans). As strains of fungi become resistant to antifungal medications, new treatment modalities must be investigated to combat these infections. One approach is to employ photodynamic therapy (PDT). PDT utilizes a photosensitizer, light, and cellular O2 to produce reactive oxygen species (ROS), which then induce oxidative stress resulting in apoptosis. Silicon phthalocyanine Pc 4 is a photosensitizer that has exhibited success in clinical trials for a myriad of skin diseases. The hydrophobic nature of Pc 4, however, poses significant formulation and delivery challenges in the use of this therapy. To mitigate these concerns, a drug delivery vehicle was synthesized to better formulate Pc 4 into a viable PDT agent for treating fungal infections. Utilizing poly(amidoamine) dendrimers as the framework for the vehicle, ∼13% of the amine chain ends were PEGylated to promote water solubility and deter nonspecific adsorption. In vitro studies with C. albicans demonstrate that the potency of Pc 4 was not hindered by the dendrimer vehicle. Encapsulated Pc 4 was able to effectively generate ROS and obliterate fungal pathogens upon photoactivation. The results presented within describe a nanoparticulate delivery vehicle for Pc 4 that readily kills drug-resistant C. albicans and eliminates solvent toxicity, thus, improving formulation characteristics for the hydrophobic photosensitizer.

  5. Modulation of biogenic amines content by poly(propylene imine) dendrimers in rats.

    Science.gov (United States)

    Ciepluch, Karol; Ziemba, Barbara; Janaszewska, Anna; Appelhans, Dietmar; Klajnert, Barbara; Bryszewska, Maria; Fogel, Wiesława Agnieszka

    2012-09-01

    Biogenic amines and polyamines participate in all vital organism functions, their levels being important function determinants. Studies were performed to check whether repeated administration of poly(propylene imine) (PPI) dendrimers, synthetic macromolecules with diaminobutane core, and peripheral primary amine groups, may influence the endogenous level of amines, as represented by the two of them: spermidine, a natural derivative of diaminobutane, and histamine. The experiment was carried out on Wistar rats. Fourth generation PPI dendrimer, as well as maltotriose-modified fourth generation PPI dendrimers with (a) cationic open sugar shell and (b) neutral dense sugar shell that possess a higher biocompatibility, was used. Applying the combination of column chromatography on Cellex P and spectrofluorimetric assays of o-phthaldialdehyde, the final amine condensation products were employed to analyze tissue spermidine and histamine outside the central nervous system. Furthermore, radioenzymatic assay was used to measure histamine levels in the brain. The obtained results indicate that in some tissues, the endogenous concentrations of histamine and spermidine may be affected by dendrimers depending on their dose and type of dendrimers.

  6. 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.

  7. 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.

  8. Dendrimer nanocarriers for transport modulation across models of the pulmonary epithelium.

    Science.gov (United States)

    Bharatwaj, Balaji; Mohammad, Abdul Khader; Dimovski, Radovan; Cassio, Fernando L; Bazito, Reinaldo C; Conti, Denise; Fu, Qiang; Reineke, Joshua; da Rocha, Sandro R P

    2015-03-02

    The purpose of this study was to determine the effect of PEGylation on the interaction of poly(amidoamine) (PAMAM) dendrimer nanocarriers (DNCs) with in vitro and in vivo models of the pulmonary epithelium. Generation-3 PAMAM dendrimers with varying surface densities of PEG 1000 Da were synthesized and characterized. The results revealed that the apical to basolateral transport of DNCs across polarized Calu-3 monolayers increases with an increase in PEG surface density. DNC having the greatest number of PEG groups (n = 25) on their surface traversed at a rate 10-fold greater than its non-PEGylated counterpart, in spite of their larger size. This behavior was attributed to a significant reduction in charge density upon PEGylation. We also observed that PEGylation can be used to modulate cellular internalization. The total uptake of PEG-free DNC into polarized Calu-3 monolayers was 12% (w/w) vs 2% (w/w) for that with 25 PEGs. Polarization is also shown to be of great relevance in studying this in vitro model of the lung epithelium. The rate of absorption of DNCs administered to mice lungs increased dramatically when conjugated with 25 PEG groups, thus supporting the in vitro results. The exposure obtained for the DNC with 25PEG was determined to be very high, with peak plasma concentrations reaching 5 μg·mL(-1) within 3 h. The combined in vitro and in vivo results shown here demonstrate that PEGylation can be potentially used to modulate the internalization and transport of DNCs across the pulmonary epithelium. Modified dendrimers thereby may serve as a valuable platform that can be tailored to target the lung tissue for treating local diseases, or the circulation, using the lung as pathway to the bloodstream, for systemic delivery.

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

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    Shainberg Asher

    2008-10-01

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

  10. Synthesis Nano Dendrimer Supramolecular with Melamine Core

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    Samaneh Maghsoodi,

    2016-12-01

    Full Text Available Dendrimers are a family of three-dimensional polymers and in nano dimension which are characterized by spherical structure. Excellent structural properties of dendrimers have distinguished them completely from linear polymers. Dendrimers have monodispersity characteristic and their size and molecular weight is controllable exactly during synthesis such as PAMAM dendrimers.Melamine can be used for synthetic core dendrimer through various methods including divergent. Melamine and related derivatives are able to form self-assembling compound via organized intramolecular networks of hydrogen bonds and provide useful molecular scaffolding components which are exploited by the field of supramolecular chemistry; which is beyond covalent bonding. In this study, the dendrimers of generated 0.5 and 1 with ester and primary amine-terminated groups with melamine and methyl acrylate were synthesized. The Synthesized dendrimer is able to form hydrogen bonding due to its nitrogen, oxygen and hydrogen atoms which was led to supramolecule characteristic. The reaction products were identified with H NMR, and 13C NMR, FT-IR, MASS spectroscopic techniques. Also nano properties of the supramoleculs were determined by X-ray diffraction method.Supramolecular characteristics of synthesized dendrimer can be studied by shifts in H-NMR peaks and also flattening of FT-IR spectrum.The synthesized dendrimer derivatives are promising for environmental and medical applications. Also, such compounds might be reacting with transition metals as ligand and could be served as catalysts.

  11. High Fluorescent Porphyrin-PAMAM-Fluorene Dendrimers.

    Science.gov (United States)

    Garfias-Gonzalez, Karla I; Organista-Mateos, Ulises; Borja-Miranda, Andrés; Gomez-Vidales, Virginia; Hernandez-Ortega, Simon; Cortez-Maya, Sandra; Martínez-García, Marcos

    2015-05-13

    Two new classes of dendrimers bearing 8 and 32 fluorene donor groups have been synthesized. The first and second generations of these porphyrin-PAMAM-fluorene dendrimers were characterized by 1H-NMR, 13C-NMR, FTIR, UV-vis spectroscopy, elemental analyses and MALDI-TOF mass spectrometry. The UV-vis spectra showed that the individual properties of donor and acceptor moieties were preserved, indicating that the new dendrimers could be used as photosynthetic antennae. Furthermore, for fluorescent spectroscopy, these dendrimers showed good energy transfer.

  12. 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.

  13. Uses of Dendrimers for DNA Microarrays

    Science.gov (United States)

    Caminade, Anne-Marie; Padié, Clément; Laurent, Régis; Maraval, Alexandrine; Majoral, Jean-Pierre

    2006-01-01

    Biosensors such as DNA microarrays and microchips are gaining an increasing importance in medicinal, forensic, and environmental analyses. Such devices are based on the detection of supramolecular interactions called hybridizations that occur between complementary oligonucleotides, one linked to a solid surface (the probe), and the other one to be analyzed (the target). This paper focuses on the improvements that hyperbranched and perfectly defined nanomolecules called dendrimers can provide to this methodology. Two main uses of dendrimers for such purpose have been described up to now; either the dendrimer is used as linker between the solid surface and the probe oligonucleotide, or the dendrimer is used as a multilabeled entity linked to the target oligonucleotide. In the first case 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 small quantities of biological entities.

  14. Vortex-Induced Alignment of a Water Soluble Supramolecular Nanofiber Composed of an Amphiphilic Dendrimer

    Directory of Open Access Journals (Sweden)

    Akihiko Tsuda

    2013-06-01

    Full Text Available We have synthesized a novel amphiphilic naphthalene imide bearing a cationic dendrimer wedge (NID. NID molecules in water self-assemble to form a two-dimensional ribbon, which further coils to give a linear supramolecular nanofiber. The sample solution showed linear dichroism (LD upon stirring of the solution, where NID nanofibers dominantly align at the center of vortex by hydrodynamic interaction with the downward torsional flows.

  15. Vortex-induced alignment of a water soluble supramolecular nanofiber composed of an amphiphilic dendrimer.

    Science.gov (United States)

    Yamamoto, Taiki; Tsuda, Akihiko

    2013-06-17

    We have synthesized a novel amphiphilic naphthalene imide bearing a cationic dendrimer wedge (NID). NID molecules in water self-assemble to form a two-dimensional ribbon, which further coils to give a linear supramolecular nanofiber. The sample solution showed linear dichroism (LD) upon stirring of the solution, where NID nanofibers dominantly align at the center of vortex by hydrodynamic interaction with the downward torsional flows.

  16. 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

  17. Conductive dendrimers obtained by click chemistry

    Science.gov (United States)

    Lewis, Donald G.; Krasnova, Larissa B.; Skinner, Philip J.; Fokin, Valery V.

    2010-08-01

    First generation dendrimers having a high level of size/shape/symmetry homogeneity were fabricated using a synthetic scheme that employs highly quantitative copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions in combination with a molecular architecture that favors homogeneity. An "outside-in" or convergent synthetic approach was employed wherein dendrons having Sierpinski triangular fractal architectures were coupled to core structures having D2h or D3h point group symmetries to form the desired dendrimers. The individual dendrons consisted of branched-backbone conductive polymers having benzene branch points and 1,2,3-triazole linkages with uninterrupted π-electron cloud overlap throughout. Each dendron was then coupled to a benzene core structure having acetylene substituents by means of a CuAAC reaction so as to extend the uninterrupted π-conjugation from the dendron to the core structure for imparting conductivity throughout the entire dendrimer. The resulting dendrimers maintained the point group symmetry of their core structure, with the core structure serving to electronically couple the dendrons to one another by extension of their uninterrupted π-electron systems. Synthesis of these first generation dendrimers provides a proof of principle for the synthesis of higher generation conductive dendrimers. Since the nanophotonic properties of conductive dendrimers may be dependent, at least in some instances, upon their size, shape, and symmetry, enhancements with respect to their homogeneity may unmask new nanophotonic properties.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Investigation of a potential macromolecular MRI contrast agent prepared from PPI (G = 2, polypropyleneimine, generation 2) dendrimer bifunctional chelates

    Science.gov (United States)

    Wang, Jianxin Steven

    The long-term objective is to develop magnetic resonance (MR) contrast agents that actively and passively target tumors for diagnosis and therapy. Many diagnostic imaging techniques for cancer lack specificity. A dendrimer based magnetic resonance imaging contrast agent has been developed with large proton relaxation enhancements and high molecular relaxivities. A new type of linear dendrimer based MRI contrast agent that is built from the polypropyleneimine and polyamidoamine dendrimers in which free amines have been conjugated to the chelate DTPA, which further formed the complex with Gadolinium (Gd) was studied. The specific research goals were to test the hypothesis that a linear chelate with macromolecular agents can be used in vitro and in vivo. This work successfully examined the adequacy and viability of the application for this agent in vitro and in vivo. A small animal whole body counter was designed and constructed to allow us to monitor biodistribution and kinetic mechanisms using a radioisotope labeled complex. The procedures of metal labeling, separation and purification have been established from this work. A biodistribution study has been performed using radioisotope induced organ/tissue counting and gamma camera imaging. The ratio of percentage of injected dose per gram organ/tissue for kidney and liver is 3.71 from whole body counter and 3.77 from the gamma camera. The results suggested that retention of Gd (III) is too high and a more kinetically stable chelate should be developed. The pharmacokinetic was evaluated in the whole animal model with the whole body clearance, and a kinetics model was developed. The pharmacokinetic results showed a bi-exponential decay in the animal model with two component excretion constants 1.43e(-5) and 0.0038511, which give half-lives of 3 hours and 33.6 days, respectively. Magnetic resonance imaging of this complex resulted in a 52% contrast enhancement in the rat kidney following the agents' administration in

  4. 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

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

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  6. 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.

  7. Targeted and pH-responsive delivery of doxorubicin to cancer cells using multifunctional dendrimer-modified multi-walled carbon nanotubes.

    Science.gov (United States)

    Wen, Shihui; Liu, Hui; Cai, Hongdong; Shen, Mingwu; Shi, Xiangyang

    2013-09-01

    We report the use of multifunctional dendrimer-modified multi-walled carbon nanotubes (MWCNTs) for targeted and pH-responsive delivery of doxorubicin (DOX) into cancer cells. In this study, amine-terminated generation 5 poly(amidoamine) (PAMAM) dendrimers modified with fluorescein isothiocyanate (FI) and folic acid (FA) were covalently linked to acid-treated MWCNTs, followed by acetylation of the remaining dendrimer terminal amines to neutralize the positive surface potential. The formed multifunctional MWCNTs (MWCNT/G5.NHAc-FI-FA) were characterized via different techniques. Then, the MWCNT/G5.NHAc-FI-FA was used to load DOX for targeted and pH-responsive delivery to cancer cells overexpressing high-affinity folic acid receptors (FAR). We showed that the MWCNT/G5.NHAc-FI-FA enabled a high drug payload and encapsulation efficiency both up to 97.8% and the formed DOX/MWCNT/G5.NHAc-FI-FA complexes displayed a pH-responsive release property with fast DOX release under acidic environment and slow release at physiological pH conditions. Importantly, the DOX/MWCNT/G5.NHAc-FI-FA complexes displayed effective therapeutic efficacy, similar to that of free DOX, and were able to target to cancer cells overexpressing high-affinity FAR and effectively inhibit the growth of the cancer cells. The synthesized multifunctional dendrimer-modified MWCNTs may be used as a targeted and pH-responsive delivery system for targeting therapy of different types of cancer cells.

  8. Synthesis of surface-modified TREN-cored PAMAM dendrimers and their effects on the solubility of sulfamethoxazole (SMZ) as an analog antibiotic drug.

    Science.gov (United States)

    Gürbüz, Mustafa Ulvi; Ertürk, Ali Serol; Tülü, Metin

    2016-09-08

    Sulfamethoxazole (SMZ) is a sulfonamide and used widely in the treatment of bacteriostatic and urinary tract infections with trimethoprim as an antibiotic. The problem with SMZ is its poor water solubility, therefore, low bioavailability in clinical applications. In this study, we synthesized new-generation Tris(2-aminoethyl)amine (TREN)-cored amine (NH2), Tris(hydroxymethyl)aminomethane (TRIS), and carboxyl (COOH) terminated different generations T2-T4 poly(amidoamine) PAMAM dendrimers. Synthesized PAMAMs were characterized by (1)H NMR, (13)C NMR, ATR-FTIR, spectroscopic titrations, and evaluated as potential solubility enhancers and drug carriers of sulfonamides by taking SMZ as a model drug. The effect of concentration, generation, and surface groups of PAMAMs on the solubility of SMZ was also investigated. Results showed that the solubility of SMZ improved significantly with an increasing generation size (T2-T4) and PAMAM dendrimer concentration (0-2 mM). The role of PAMAMs in the solubility enhancement of SMZ was in the order of T4.NH2 > T4.COOH > T3.NH2 > T4.TRIS > T2.NH2 > T3.COOH > T3.TRIS > T2.COOH > T2.TRIS, and in the ranges of 5- to 45-fold with maximum SMZ loading 7 to 61 mole/mole per PAMAM dendrimer molecule. In vitro release studies demonstrated that SMZ-PAMAM dendrimer complexes at the end of 2-h drug release (16-26%) was considerable slower than pure SMZ (38.8%).

  9. The complex of PAMAM-OH dendrimer with Angiotensin (1–7) prevented the disuse-induced skeletal muscle atrophy in mice

    Science.gov (United States)

    Márquez-Miranda, Valeria; Abrigo, Johanna; Rivera, Juan Carlos; Araya-Durán, Ingrid; Aravena, Javier; Simon, Felipe; Pacheco, Nicolás; González-Nilo, Fernando Danilo; Cabello-Verrugio, Claudio

    2017-01-01

    Angiotensin (1–7) (Ang-(1–7)) is a bioactive heptapeptide with a short half-life and has beneficial effects in several tissues – among them, skeletal muscle – by preventing muscle atrophy. Dendrimers are promising vehicles for the protection and transport of numerous bioactive molecules. This work explored the use of a neutral, non-cytotoxic hydroxyl-terminated poly(amidoamine) (PAMAM-OH) dendrimer as an Ang-(1–7) carrier. Bioinformatics analysis showed that the Ang-(1–7)-binding capacity of the dendrimer presented a 2:1 molar ratio. Molecular dynamics simulation analysis revealed the capacity of neutral PAMAM-OH to protect Ang-(1–7) and form stable complexes. The peptide coverage ability of the dendrimer was between ~50% and 65%. Furthermore, an electrophoretic mobility shift assay demonstrated that neutral PAMAM-OH effectively bonded peptides. Experimental results showed that the Ang-(1–7)/PAMAM-OH complex, but not Ang-(1–7) alone, had an anti-atrophic effect when administered intraperitoneally, as evaluated by muscle strength, fiber diameter, myofibrillar protein levels, and atrogin-1 and MuRF-1 expressions. The results of the Ang-(1–7)/PAMAM-OH complex being intraperitoneally injected were similar to the results obtained when Ang-(1–7) was systemically administered through mini-osmotic pumps. Together, the results suggest that Ang-(1–7) can be protected for PAMAM-OH when this complex is intraperitoneally injected. Therefore, the Ang-(1–7)/PAMAM-OH complex is an efficient delivery method for Ang-(1–7), since it improves the anti-atrophic activity of this peptide in skeletal muscle. PMID:28331320

  10. 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.

  11. Oligothia dendrimers for the formation of gold nanoparticles

    NARCIS (Netherlands)

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

    2004-01-01

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

  12. High performance dendrimer functionalized single-walled carbon nanotubes field effect transistor biosensor for protein detection

    Science.gov (United States)

    Rajesh, Sharma, Vikash; Puri, Nitin K.; Mulchandani, Ashok; Kotnala, Ravinder K.

    2016-12-01

    We report a single-walled carbon nanotube (SWNT) field-effect transistor (FET) functionalized with Polyamidoamine (PAMAM) dendrimer with 128 carboxyl groups as anchors for site specific biomolecular immobilization of protein antibody for C-reactive protein (CRP) detection. The FET device was characterized by scanning electron microscopy and current-gate voltage (I-Vg) characteristic studies. A concentration-dependent decrease in the source-drain current was observed in the regime of clinical significance, with a detection limit of ˜85 pM and a high sensitivity of 20% change in current (ΔI/I) per decade CRP concentration, showing SWNT being locally gated by the binding of CRP to antibody (anti-CRP) on the FET device. The low value of the dissociation constant (Kd = 0.31 ± 0.13 μg ml-1) indicated a high affinity of the device towards CRP analyte arising due to high anti-CRP loading with a better probe orientation on the 3-dimensional PAMAM structure.

  13. PREPARATION OF CHEMICALLY WELL-DEFINED CARBOHYDRATE DENDRIMER CONJUGATES

    DEFF Research Database (Denmark)

    2004-01-01

    A method for the synthesis of dendrimer conjugates having a well-defined chemical structure, comprising one or more carbohydrate moieties and one or more immunomodulating substances coupled to a dendrimer, is presented. First, the carbohydrate is bound to the dendrimer in a chemoselective manner....... Subsequently, the immunomodulating substance is also bound in a chemoselective manner, to give a dendrimer conjugate with a well-defined structure and connectivity and containing a precise, pre-determined ratio of carbohydrate to immunomodulating substance. The invention also relates to novel dendrimer...

  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. 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).

  16. 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.

  17. 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.

  18. Dendrimers for Vaccine and Immunostimulatory Uses

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  19. 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

  20. 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.

  1. 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.

  2. Preparation of well-defined dendrimer encapsulated ruthenium nanoparticles and their evaluation in the reduction of 4-nitrophenol according to the Langmuir-Hinshelwood approach.

    Science.gov (United States)

    Antonels, Nathan Charles; Meijboom, Reinout

    2013-11-05

    This study discusses the preparation of various sized dendrimer encapsulated ruthenium nanoparticles (RuDEN) with the use of the generation 4 (G4), generation 5 (G5), and generation 6 (G6) hydroxyl-terminated poly(amidoamine) (PAMAM-OH) dendrimers as templating agents. The size of the nanoparticles ranges from 1.1 to 2.2 nm. These catalysts were fully characterized using UV/vis spectrophotometry, infrared (IR) spectroscopy, and transmission electron microscopy (TEM). The RuDEN catalysts were evaluated in the reduction of 4-nitrophenol (4NP) in the presence of sodium borohydride (BH4(-)) for various concentrations of either. The kinetic data obtained were modeled to the Langmuir-Hinshelwood equation. The model allows the relation of the apparent rate constant to the total surface area S of the nanoparticle, the kinetic constant k which is related to the rate-determining step, and the adsorption constants K(4NP) and K(BH4) for 4NP and borohydride, respectively. These parameters were calculated for each of the RuDENs, proving the Langmuir-Hinshelwood model to be suitable for the kinetic evaluation of RuDENs in the catalytic reduction of 4NP.

  3. 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.

  4. Fluorescent Self-Assembled Polyphenylene Dendrimer Nanofibers

    NARCIS (Netherlands)

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

    2003-01-01

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

  5. Dendrimer effects on peptide and protein fibrillation

    DEFF Research Database (Denmark)

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

    2007-01-01

    Dendrimers are synthetic, symmetrically branched polymers that can be manufactured to a high degree of definition and therefore present themselves as monodisperse entities. Flexible and globular in shape and compartementalized into a partly inaccessible interior and a highly exposed surface, they...

  6. Study of the interactions of PAMAM G3-NH2 and G3-OH dendrimers with 5-fluorouracil in aqueous solutions.

    Science.gov (United States)

    Buczkowski, Adam; Waliszewski, Dariusz; Urbaniak, Pawel; Palecz, Bartlomiej

    2016-05-30

    The results of spectroscopic measurements (increase in solubility, equilibrium dialysis, (1)H NMR titration) and calorimetric measurements (isothermal titration ITC) indicate spontaneous (ΔG<0) bonding of 5-fluorouracil by both cationic PAMAM G3-NH2 dendrimer and hydroxyl PAMAM G3-OH dendrimer in aqueous solutions. PAMAM G3-NH2 dendrimer bonds about n= 25±8 drug molecules. Some of them n1= 5±1 are bonded by terminal amine groups with equilibrium constant K1= 3890±930, while the remaining ones n2= 24 ±3 are bonded by amide groups with equilibrium constant K2= 110±30. Hydroxyl PAMAM G3-OH dendrimer bonds n=6.0±1.6 molecules of 5-fluorouracil through tertiary amine groups with equilibrium constant K= 65±10. The parameters of bonding 5-fluorouracil by PAMAM G3-NH2 and G3-OH dendrimer were compared with those of bonding this drug by the macromolecules of PAMAM of generations G4-NH2, G5-NH2 and G5-OH.

  7. 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.

  8. Modulated regeneration of acid-etched human tooth enamel by a functionalized dendrimer that is an analog of amelogenin.

    Science.gov (United States)

    Chen, Mei; Yang, Jiaojiao; Li, Jiyao; Liang, Kunneng; He, Libang; Lin, Zaifu; Chen, Xingyu; Ren, Xiaokang; Li, Jianshu

    2014-10-01

    In the bioinspired repair process of tooth enamel, it is important to simultaneously mimic the organic-matrix-induced biomineralization and increase the binding strength at the remineralization interface. In this work, a fourth-generation polyamidoamine dendrimer (PAMAM) is modified by dimethyl phosphate to obtain phosphate-terminated dendrimer (PAMAM-PO3H2) since it has a similar dimensional scale and peripheral functionalities to that of amelogenin, which plays important role in the natural development process of enamel. Its phosphate group has stronger affinity for calcium ion than carboxyl group and can simultaneously provide strong hydroxyapatite (HA)-binding capability. The MTT assay demonstrates the low cytotoxicity of PAMAM-PO3H2. Adsorption tests indicate that PAMAM-PO3H2 can be tightly adsorbed on the human tooth enamel. Scanning electron microscopy and X-ray diffraction are used to analyze the remineralization process. After being incubated in artificial saliva for 3weeks, there is a newly generated HA layer of 11.23μm thickness on the acid-etched tooth enamel treated by PAMAM-PO3H2, while the thickness for the carboxyl-terminated one (PAMAM-COOH) is only 6.02μm. PAMAM-PO3H2 can regulate the remineralization process to form ordered new crystals oriented along the Z-axis and produce an enamel prism-like structure that is similar to that of natural tooth enamel. The animal experiment also demonstrates that PAMAM-PO3H2 can induce significant HA regeneration in the oral cavity of rats. Thus PAMAM-PO3H2 shows great potential as a biomimetic restorative material for human tooth enamel.

  9. Multifunctional polyamidoamine-modified selenium nanoparticles dual-delivering siRNA and cisplatin to A549/DDP cells for reversal multidrug resistance.

    Science.gov (United States)

    Zheng, Wenjing; Cao, Chengwen; Liu, Yanan; Yu, Qianqian; Zheng, Chuping; Sun, Dongdong; Ren, Xiaofan; Liu, Jie

    2015-01-01

    Multidrug resistance (MDR) is a major barrier against effective cancer treatment. Dual-delivering a therapeutic small interfering RNA (siRNA) and chemotherapeutic agents has been developed to reverse drug resistance in tumor cells. In this study, amine-terminated generation 5 polyamidoamine (PAMAM) dendrimers (G5.NH2)-modified selenium nanoparticles (G5@Se NP) were synthesized for the systemic dual-delivery of mdr1 siRNA and cisplatin (cis-diamminedichloroplatinum-(II), DDP), which was demonstrated to enhance siRNA loading, releasing efficiency and gene-silencing efficacy. When the mdr1 siRNA was conjugated with G5@Se NP via electrostatic interaction, a significant down-regulation of P-glycoprotein and multidrug resistance-associated protein expression was observed; G5@Se-DDP-siRNA arrested A549/DDP cells at G1 phase and led to enhanced cytotoxicity in A549/DDP cells through induction of apoptosis involving the AKT and ERK signaling pathways. Interestingly, G5@Se-DDP NP were much less reactive than DDP in the reactions with both MT and GSH, indicating that loading of DDP in a nano-delivery system could effectively prevent cell detoxification. Furthermore, animal studies demonstrated that the new delivery system of G5@Se-DDP-siRNA significantly enhanced the anti-tumor effect on tumor-bearing nude mice, with no appreciable abnormality in the major organs. These results suggest that G5@Se NP could be a potential platform to combine chemotherapy and gene therapy technology in the treatment of human disease.

  10. 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.

  11. 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...

  12. 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.

  13. Smart bomb AS1411 aptamer-functionalized/PAMAM dendrimer nanocarriers for targeted drug delivery in the treatment of gastric cancer.

    Science.gov (United States)

    Barzegar Behrooz, Amir; Nabavizadeh, Fatemeh; Adiban, Jamal; Shafiee Ardestani, Mehdi; Vahabpour, Rouhollah; Aghasadeghi, Mohammad Reza; Sohanaki, Hamid

    2017-01-01

    Chemotherapy, a conventional method assessed in recent oncology studies, poses numerous problems in the clinical environment. To overcome the problems inherent in chemotherapy, an intelligent drug delivery system has come to the forefront of cancer therapeutics. In this study, we designed a dendrimer-based pharmaceutical system together with a single-stranded AS1411 aptamer (APT(AS)(1411) ) as a therapeutic strategy. The polyamidoamine (PAMAM)-polyethylene glycol (PEG) complex was then conjugated with the AS1411 aptamer and confirmed by atomic-force microscopy (AFM) and Fourier transform infrared spectroscopy (FTIR) .In this study, we show that the conjugated PAMAM-PEG-APT(AS)(1411) complex dramatically increased PAMAM-PEG-5-FU uptake by MKN45 gastric cancer cells. We also demonstrated both the stability of the nanoparticle-5-FU-APT(AS)(1411) complex, by thin layer chromatography (TLC), and an increase in 5-fluorouracil (5-FU) accumulation in the vicinity of cancerous tumors. This smart drug delivery system is capable of effectively transferring 5-FU to MKN45 gastric cancer cells in consistent and without toxic effects.

  14. 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.

  15. Self-Aggregation of Amphiphilic Dendrimer in Aqueous Solution: The Effect of Headgroup and Hydrocarbon Chain Length.

    Science.gov (United States)

    Zhang, Pei; Xu, Xiaohui; Zhang, Minghui; Wang, Jinben; Bai, Guangyue; Yan, Haike

    2015-07-28

    The self-aggregation of amphiphilic dendrimers G1QPAMCm based on poly(amidoamine) PAMAM possessing the same hydrophilic group but differing in alkyl chain length in aqueous solution was investigated. Differences in the chemical structures lead to significant specificities in the aggregate building process. A variety of physicochemical parameters presented monotonous regularity with the increase in alkyl chain length in multibranched structure, as traditional amphiphilic molecules. A significant difference, however, existed in the morphology and the microenvironment of the microdomain of the aggregates, with G1QPAMCm with an alkyl chain length of 16 intending to form vesicles. To obtain supporting information about the aggregation mechanism, the thermodynamic parameters of micellization, the free Gibbs energy ΔGmic, and the entropy ΔSmic were derived subsequently, of which the relationship between the hydrophobic chain length and the thermodynamic properties indicated that the self-assembly process was jointly driven by enthalpy and entropy. Other than traditional surfactants, the contribution of enthalpy has not increased identically to the increase in hydrophobic interactions, which depends on the ratio of the alkyl chain length to the radius in the headgroup. Continuous increases in the hydrophobic chain length from 12 to 16 lead to the intracohesion of the alkyl chain involved in the process of self-assembly, weakening the hydrophobic interactions, and the increase in -ΔHmic, which offers an explanation of the formation of vesicular structures.

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

    Energy Technology Data Exchange (ETDEWEB)

    Mejri-Omrani, Nawel [ICMMO, CNRS, Université Paris-Saclay, Equipe de Chimie Bio-organique et Bio-inorganique, Bâtiment 420, 91405 Orsay (France); BAE, Université de Perpignan, 52 Avenue Paul Alduy, 66860 Perpignan (France); Université de Carthage, National Institute of Applied Sciences and Technology (INSAT) Laboratoire d' Ecologie et de Technologie Microbiennes (LETMi), 1080 Tunis (Tunisia); Miodek, Anna; Zribi, Becem [ICMMO, CNRS, Université Paris-Saclay, Equipe de Chimie Bio-organique et Bio-inorganique, Bâtiment 420, 91405 Orsay (France); Marrakchi, Mouna [Université de Carthage, National Institute of Applied Sciences and Technology (INSAT) Laboratoire d' Ecologie et de Technologie Microbiennes (LETMi), 1080 Tunis (Tunisia); Université de Tunis El Manar, Higher Institute of Applied Biological Sciences (ISSBAT), 1006 Tunis (Tunisia); Hamdi, Moktar [Université de Carthage, National Institute of Applied Sciences and Technology (INSAT) Laboratoire d' Ecologie et de Technologie Microbiennes (LETMi), 1080 Tunis (Tunisia); Marty, Jean-Louis [BAE, Université de Perpignan, 52 Avenue Paul Alduy, 66860 Perpignan (France); Korri-Youssoufi, Hafsa, E-mail: hafsa.korri-youssoufi@u-psud.fr [ICMMO, CNRS, Université Paris-Saclay, Equipe de Chimie Bio-organique et Bio-inorganique, Bâtiment 420, 91405 Orsay (France)

    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{sup −1} of OTA and a detection limit of 2 ng L{sup −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. - Highlights: • Development of innovative platform for direct and ultra-sensitive toxins detection. • Aptasensor based on modified conductive polypyrrole layer. • We demonstrate the conformation change of aptamer upon toxin binding. • We highlight that detection was obtained by modification of charge of

  17. IMMUNOSTIMULATORY PROPERTIES OF DENDRIMERS MULTIVALENTLY PRESENTING MURAMYLDIPEPTIDE

    DEFF Research Database (Denmark)

    Objectives: Many pathogens will only be efficiently neutralized by the induction of cell-mediated immunity, and with the enhanced use of subunit-vaccine approaches there is a strong need for the development of efficient and safe Th1-biassing adjuvants. Pathogen-associated molecular patterns (PAMP...... to employ dendrimers in the synthesis of molecularly defined globular PAMP-mimics or “artificial microbes” with controlled immunostimulatory properties....

  18. 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.

  19. 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.

  20. Periphery-Functionalized Organometallic Dendrimers for Homogeneous Catalysis

    NARCIS (Netherlands)

    Koten, G. van; Jastrzebski, J.T.B.H.

    1999-01-01

    The use of carbosilane based dendrimers as molecular scaffolds for the attachment of organomettallic Ni 'pincer' complexes that are active as a catalyst in the Kharasch addition reaction is described. It is shown that increasing steric crowding at the dendrimer periphery results in decreased catalys

  1. Synthesis of Novel Carbosilane Dendrimers with Myo-inositol Cores

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The preparation of carbosilane dendrimers with cores of myo-inositol and the outmost periphery groups of allyl groups has been reported.By using alternate hydrosilylation and alkenylation reactions, the dendrimer have been carried up to the third generation with 48 allyl groups on the periphery.

  2. 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.

  3. Synthesis and Spectral Studies of CdTe-Dendrimer Conjugates

    Science.gov (United States)

    Ghosh, Srabanti; Saha, Abhijit

    2009-08-01

    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.

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

    Science.gov (United States)

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

    2011-02-01

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

  5. The complex of PAMAM-OH dendrimer with Angiotensin (1–7 prevented the disuse-induced skeletal muscle atrophy in mice

    Directory of Open Access Journals (Sweden)

    Márquez-Miranda V

    2017-03-01

    Full Text Available Valeria Márquez-Miranda,1,2,* Johanna Abrigo,3,4,* Juan Carlos Rivera,3,4 Ingrid Araya-Durán,1 Javier Aravena,3,4 Felipe Simon,3,4 Nicolás Pacheco,1 Fernando Danilo González-Nilo,1,2,5 Claudio Cabello-Verrugio3,4 1Center for Bioinformatics and Integrative Biology (CBIB, Facultad de Ciencias Biologicas, Universidad Andres Bello, Santiago, 2Fundación Fraunhofer Chile Research, Las Condes, 3Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas & Facultad de Medicina, Universidad Andres Bello, 4Millennium Institute on Immunology and Immunotherapy, Santiago, 5Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile *These authors contributed equally to this work Abstract: Angiotensin (1–7 (Ang-(1–7 is a bioactive heptapeptide with a short half-life and has beneficial effects in several tissues – among them, skeletal muscle – by preventing muscle atrophy. Dendrimers are promising vehicles for the protection and transport of numerous bioactive molecules. This work explored the use of a neutral, non-cytotoxic hydroxyl-terminated poly(amidoamine (PAMAM-OH dendrimer as an Ang-(1–7 carrier. Bioinformatics analysis showed that the Ang-(1–7-binding capacity of the dendrimer presented a 2:1 molar ratio. Molecular dynamics simulation analysis revealed the capacity of neutral PAMAM-OH to protect Ang-(1–7 and form stable complexes. The peptide coverage ability of the dendrimer was between ~50% and 65%. Furthermore, an electrophoretic mobility shift assay demonstrated that neutral PAMAM-OH effectively bonded peptides. Experimental results showed that the Ang-(1–7/PAMAM-OH complex, but not Ang-(1–7 alone, had an anti-atrophic effect when administered intraperitoneally, as evaluated by muscle strength, fiber diameter, myofibrillar protein levels, and atrogin-1 and MuRF-1 expressions. The results of the Ang-(1–7/PAMAM-OH complex being intraperitoneally

  6. Potential inhibition of HIV-1 encapsidation by oligoribonucleotide–dendrimer nanoparticle complexes

    Science.gov (United States)

    Parboosing, Raveen; Chonco, Louis; de la Mata, Francisco Javier; Govender, Thavendran; Maguire, Glenn EM; Kruger, Hendrik G

    2017-01-01

    Background Encapsidation, the process during which the genomic RNA of HIV is packaged into viral particles, is an attractive target for antiviral therapy. This study explores a novel nanotechnology-based strategy to inhibit HIV encapsidation by an RNA decoy mechanism. The design of the 16-mer oligoribonucleotide (RNA) decoy is based on the sequence of stem loop 3 (SL3) of the HIV packaging signal (Ψ). Recognition of the packaging signal is essential to the encapsidation process. It is theorized that the decoy RNA, by mimicking the packaging signal, will disrupt HIV packaging if efficiently delivered into lymphocytes by complexation with a carbosilane dendrimer. The aim of the study is to measure the uptake, toxicity, and antiviral activity of the dendrimer–RNA nanocomplex. Materials and methods A dendriplex was formed between cationic carbosilane dendrimers and the RNA decoy. Uptake of the fluorescein-labeled RNA into MT4 lymphocytes was determined by flow cytometry and confocal microscopy. The cytoprotective effect (50% effective concentration [EC50]) and the effect on HIV replication were determined in vitro by the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and viral load measurements, respectively. Results Flow cytometry and confocal imaging demonstrated efficient transfection of lymphocytes. The dendriplex containing the Ψ decoy showed some activity (EC50 =3.20 µM, selectivity index =8.4). However, there was no significant suppression of HIV viral load. Conclusion Oligoribonucleotide decoys containing SL3 of the packaging sequence are efficiently delivered into lymphocytes by carbosilane dendrimers where they exhibit a modest cytoprotective effect against HIV infection. PMID:28115849

  7. Photochromism of 36-Armed Liquid Crystalline Dendrimer

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The photochromism of a 36-armed liquid crystalline dendrimer D6 was briefly described in this paper. The molar absorption coefficient, photoisomerization and photo back-isomerization of D6 in solution were investigated by UV/Vis absorption spectra. The results indicate that the photochromism and photo back-isomerization of D6 in chloroform (CHCl3) and tetrahydrofuran (THF) solutions are in accordance with the first order kinetics. The photochromism rate constants of D6 are 10-1 s-1, it is 107 times larger than that of side-chain liquid crystalline polymers containing the same azobenzene moieties.

  8. Biological Activity of Mesoporous Dendrimer-Coated Titanium Dioxide: Insight on the Role of the Surface-Interface Composition and the Framework Crystallinity.

    Science.gov (United States)

    Milowska, Katarzyna; Rybczyńska, Aneta; Mosiolek, Joanna; Durdyn, Joanna; Szewczyk, Eligia M; Katir, Nadia; Brahmi, Younes; Majoral, Jean-Pierre; Bousmina, Mosto; Bryszewska, Maria; El Kadib, Abdelkrim

    2015-09-16

    Hitherto, the field of nanomedicine has been overwhelmingly dominated by the use of mesoporous organosilicas compared to their metal oxide congeners. Despite their remarkable reactivity, titanium oxide-based materials have been seldom evaluated and little knowledge has been gained with respect to their "structure-biological activity" relationship. Herein, a fruitful association of phosphorus dendrimers (both "ammonium-terminated" and "phosphonate-terminated") and titanium dioxide has been performed by means of the sol-gel process, resulting in mesoporous dendrimer-coated nanosized crystalline titanium dioxide. A similar organo-coating has been reproduced using single branch-mimicking dendrimers that allow isolation of an amorphous titanium dioxide. The impact of these materials on red blood cells was evaluated by studying cell hemolysis. Next, their cytotoxicity toward B14 Chinese fibroblasts and their antimicrobial activity were also investigated. Based on their variants (cationic versus anionic terminal groups and amorphous versus crystalline titanium dioxide phase), better understanding of the role of the surface-interface composition and the nature of the framework has been gained. No noticeable discrimination was observed for amorphous and crystalline material. In contrast, hemolysis and cytotoxicity were found to be sensitive to the nature of the interface composition, with the ammonium-terminated dendrimer-coated titanium dioxide being the most hemolytic and cytotoxic material. This surface-functionalization opens the door for creating a new synergistic machineries mechanism at the cellular level and seems promising for tailoring the biological activity of nanosized organic-inorganic hybrid materials.

  9. 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.

  10. 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.

  11. Dendrimers - from organic synthesis to pharmaceutical applications: an update.

    Science.gov (United States)

    Kalhapure, Rahul S; Kathiravan, Muthu K; Akamanchi, Krishnacharya G; Govender, Thirumala

    2015-01-01

    Dendrimers are a relatively new class of monodisperse polymers, which have tree-like spherical structures with well-defined sizes and shapes. Their unique structure has a significant impact on their physical and chemical properties. Research on dendrimers is of significant interest to scientists from all areas and their utility in various scientific fields, including pharmaceuticals, is expanding. The present review is comprehensive and covers different aspects of dendrimers viz. (1) synthesis, (2) properties and (3) pharmaceutical applications. The emphasis is on their applications as well as the current ongoing research status for drug targeting.

  12. 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.

  13. Biomimetic poly(amidoamine hydrogels as synthetic materials for cell culture

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    Lenardi Cristina

    2008-11-01

    Full Text Available Abstract Background Poly(amidoamines (PAAs are synthetic polymers endowed with many biologically interesting properties, being highly biocompatible, non toxic and biodegradable. Hydrogels based on PAAs can be easily modified during the synthesis by the introduction of functional co-monomers. Aim of this work is the development and testing of novel amphoteric nanosized poly(amidoamine hydrogel film incorporating 4-aminobutylguanidine (agmatine moieties to create RGD-mimicking repeating units for promoting cell adhesion. Results A systematic comparative study of the response of an epithelial cell line was performed on hydrogels with agmatine and on non-functionalized amphoteric poly(amidoamine hydrogels and tissue culture plastic substrates. The cell adhesion on the agmatine containing substrates was comparable to that on plastic substrates and significantly enhanced with respect to the non-functionalized controls. Interestingly, spreading and proliferation on the functionalized supports are slower than on plastic exhibiting the possibility of an easier control of the cell growth kinetics. In order to favor the handling of the samples, a procedure for the production of bi-layered constructs was also developed by means the deposition via spin coating of a thin layer of hydrogel on a pre-treated cover slip. Conclusion The obtained results reveal that PAAs hydrogels can be profitably functionalized and, in general, undergo physical and chemical modifications to meet specific requirements. In particular the incorporation of agmatine warrants good potential in the field of cell culturing and the development of supported functionalized hydrogels on cover glass are very promising substrates for applications in cell screening devices.

  14. From dendrimers to fractal polymers and beyond

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    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.

  15. 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.

  16. Thermodynamic properties of a liquid crystal carbosilane dendrimer

    Science.gov (United States)

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

    2016-11-01

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

  17. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Han, Seung Choul; Lee, Jae Wook [Dong-A Univ., Busan (Korea, Republic of); Jin, Sungho [Pusan National Univ., Busan (Korea, Republic of)

    2012-10-15

    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

  19. 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.

  20. 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

  1. 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.

  2. Carbosilane dendrimers bearing globotriaoses: syntheses of globotrioasyl derivative and introduction into carbosilane dendrimers.

    Science.gov (United States)

    Matsuoka, Koji; Terabatake, Mikiko; Umino, Atsushi; Esumi, Yasuaki; Hatano, Ken; Terunuma, Daiyo; Kuzuhara, Hiroyoshi

    2006-08-01

    As an application of a one-pot reaction involving Birch reduction and subsequent S(N)2 reaction in liquid ammonia, synthetic assembly of trisaccharidic moieties of globotriaosyl ceramide onto carbosilane dendrimers was accomplished using tris(3-bromopropyl)phenylsilane and tris[tris(3-bromopropyl)silylpropyl]phenylsilane as the core scaffolds. The common globotriaosyl derivative having benzylsulfide functionality at the terminal of the aglycon was efficiently prepared from d-galactose and d-lactose as starting materials. The glycosyl donor derived from galactose and the glycosyl acceptor derived from lactose were condensed in the presence of silver triflate as the best promoter to provide corresponding trisaccharide with newly formed alpha-1-4 linkages in 90% yield. Fully benzylated protection of the trisaccharide was deprotected under the Birch reduction condition followed by acetylation to give an acetate in which alkene was converted into benzyl sulfide by radical addition of alpha-toluenethiol in high yields. On the other hand, carbosilane dendrimers were prepared from appropriate chlorosilanes as starting materials by a combination of hydrosylation followed by alkenylation. The terminal C=C double bonds of the carbosilanes were converted into corresponding alcohols by means of the usual hydroboration reaction, and the alcohols underwent further chemical manipulation to give carbosilane dendrimers with peripheral bromine atoms.

  3. 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.

  4. Conformational Analysis of Triazine Dendrimers: Using NMR Spectroscopy To Probe the Choreography of a Dendrimer's Dance.

    Science.gov (United States)

    Moreno, Karlos X; Simanek, Eric E

    2008-06-24

    One-dimensional (1D) and two-dimensional (2D) NMR studies are used to probe the conformation of a melamine dendrimer bearing unique NMR signals from the core to the periphery. Four conceptual anchors for dendrimer conformation emerge from these experiments. First, changes in isomer populations observed by (1)H NMR reveal the onset of globular structure. Second, NOE complexity emerges with globular structure: variable temperature NOESY studies show that the peripheral groups, BOC-protected aliphatic amines, fold back into the globular core of the macromolecule at 75 degrees C in DMSO-d(6). Third, variable temperature coefficients measured for NH protons suggest that solvent is largely excluded from the interior of the dendrimer: the carbamate NH groups of the periphery are most sensitive to temperature while the NHs nearest the core show little temperature dependence. Conformation is influenced by solvent choice: backfolding is observed in DMSO-d(6), but not in either CDCl(3) or CD(3)OD. Finally, relaxation studies show that peripheral groups are more dynamic than groups at the core. These anchors consolidate observations made by many groups on disparate systems within a common architecture.

  5. 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.

  6. Development of Topical Treatment for Pseudomonas aeruginosa Wound Infections by Quorum-Sensing Inhibitors Mediated by Poly(amidoamine) (PAMAM) Dendrimers

    Science.gov (United States)

    2013-01-01

    5), turnover of PAMAM in PA (Task 6), quinolone signals by HPLC-MS (Task 7), and extracellular virulence factors (Task 8). The most significant...PAMAM on PqsA activity PqsA is the first enzyme in quinolone synthetic pathway (3). Anthranilic acid (AA) is a substrate for PqsA. AA analogs...Measurement of secreted QS signals All AA analogs significantly inhibited secreted quinolone signals but not the acylhomoserine lactone signals using

  7. 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.

  8. 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

  9. Photoactivity and pH sensitivity of methyl orange functionalized poly(propyleneamine) dendrimers

    NARCIS (Netherlands)

    Dirksen, A.; Zuidema, E.; Williams, R.M.; De Cola, L.; Kauffmann, C.; Vögtle, F.; Roque, A.; Pina, F.

    2002-01-01

    For the first time a pH indicator that responds to two different external stimuli, i.e. pH and light, namely methyl orange, has been implemented in a dendrimer. Six generations (G0-G5) of methyl orange-functionalized poly(propyleneamine) dendrimers ("MO dendrimers") have been synthesized and charact

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

    Directory of Open Access Journals (Sweden)

    Michael Müller

    2016-08-01

    Full Text Available 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.

  11. N-Acetylgalactosamine-Targeted Delivery of Dendrimer-Doxorubicin Conjugates Influences Doxorubicin Cytotoxicity and Metabolic Profile in Hepatic Cancer Cells.

    Science.gov (United States)

    Kuruvilla, Sibu P; Tiruchinapally, Gopinath; ElAzzouny, Mahmoud; ElSayed, Mohamed E H

    2017-03-01

    This study describes the development of targeted, doxorubicin (DOX)-loaded generation 5 (G5) polyamidoamine dendrimers able to achieve cell-specific DOX delivery and release into the cytoplasm of hepatic cancer cells. G5 is functionalized with poly(ethylene glycol) (PEG) brushes displaying N-acetylgalactosamine (NAcGal) ligands to target hepatic cancer cells. DOX is attached to G5 through one of two aromatic azo-linkages, L3 or L4, achieving either P1 ((NAcGalβ -PEGc)16.6 -G5-(L3-DOX)11.6 ) or P2 ((NAcGalβ -PEGc)16.6 -G5-(L4-DOX)13.4 ) conjugates. After confirming the conjugates' biocompatibility, flow cytometry studies show P1/P2 achieve 100% uptake into hepatic cancer cells at 30-60 × 10(-9) m particle concentration. This internalization correlates with cytotoxicity against HepG2 cells with 50% inhibitory concentration (IC50 ) values of 24.8, 1414.0, and 237.8 × 10(-9) m for free DOX, P1, and P2, respectively. Differences in cytotoxicity prompted metabolomics analysis to identify the intracellular release behavior of DOX. Results show that P1/P2 release alternative DOX metabolites than free DOX. Stable isotope tracer studies show that the different metabolites induce different effects on metabolic cycles. Namely, free DOX reduces glycolysis and increases fatty acid oxidation, while P1/P2 increase glycolysis, likely as a response to high oxidative stress. Overall, P1/P2 conjugates offer a platform drug delivery technology for improving hepatic cancer therapy.

  12. 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.

  13. Biological performance of a novel biodegradable polyamidoamine hydrogel as guide for peripheral nerve regeneration.

    Science.gov (United States)

    Magnaghi, Valerio; Conte, Vincenzo; Procacci, Patrizia; Pivato, Giorgio; Cortese, Paolo; Cavalli, Erika; Pajardi, Giorgio; Ranucci, Elisabetta; Fenili, Fabio; Manfredi, Amedea; Ferruti, Paolo

    2011-07-01

    Polyamidoamines (PAAs) are a well-known family of synthetic biocompatible and biodegradable polymers, which can be prepared as soft hydrogels characterized by low interfacial tension and tunable elasticity. For the first time we report here on the in vivo performance of a PAA hydrogel implant as scaffold for tissue engineering. In particular, an amphoteric agmatine-deriving PAA hydrogel shaped as small tubing was obtained by radical polymerization of a soluble functional oligomeric precursor and used as conduit for nerve regeneration in a rat sciatic nerve cut model. The animals were analyzed at 30, 90, and 180 days post-surgery. PAA tubing proved to facilitate nerve regeneration. Good surgical outcomes were achieved with no signs of inflammation or neuroma. Moreover, nerve regeneration was morphologically sound and the quality of functional recovery satisfactory. In conclusion, PAA hydrogel scaffolds may represent a novel and promising material for peripheral nerve regeneration.

  14. Structural properties of star-like dendrimers in solution

    Energy Technology Data Exchange (ETDEWEB)

    Rathgeber, S. [Forschungszentrum Juelich GmbH, IFF Weiche Materie, 52425 Juelich (Germany); Gast, A.P. [Stanford University, Stanford, CA 94305-5025 (United States); Hedrick, J.L. [IBM Almaden Research Center, San Jose, CA 95120-6099 (United States)

    2002-07-01

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

  15. Structural properties of star-like dendrimers in solution

    Science.gov (United States)

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

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

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

    Science.gov (United States)

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

    2015-05-20

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

  17. 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.

  18. 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.

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

    Science.gov (United States)

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

    2016-06-24

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

  20. 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.

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

    Science.gov (United States)

    Martínez-Klimov, Mark Euguenii; Organista-Mateos, Ulises; Borja-Miranda, Andrés; Rivera, Margarita; Amelines-Sarria, Oscar; Martínez-García, Marcos

    2015-09-22

    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.

  2. 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.

  3. 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.

  4. Preparation and termination of carbosilane dendrimer based on siloxane tetramer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chung Kyun; Park, Eun Mi [Donga Univ., Pusan (Korea, Republic of)

    1998-02-01

    Dendritic macromolecules of the first to fourth generation were synthesized, using alkenylation and hydrosilation cycles with allylmagnesium bromide and dichloromethylsilane as building blocks and siloxane tetramer (Me(CH{sub 2}=CH)SiO){sub 4} as core molecule. By the reaction of the dichloromethylsilyl-capped generation (G4P) with p-bromophenol, p-phenylphenol and lithium phenyethynylide, dendrimers with specific functions (G4P-BP) (Mw: 16,300), G4P-PP (16,121), and G4P-PA (11,764) have been produced. Analysis of new dendrimers by NMR, UV and MALDI mass spectrometry suggests that they are pure and unified.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. Polyphenylene Dendrimers with Perylene Diimide as a Luminescent Core

    NARCIS (Netherlands)

    Herrmann, Andreas; Weil, Tanja; Sinigersky, Veselin; Wiesler, Uwe-Martin; Vosch, Tom; Hofkens, Johan; Schryver, Frans C. De; Müllen, Klaus

    2001-01-01

    A novel synthesis is presented of a fourfold ethynyl-substituted perylene diimide dye 4, which acts as a core molecule for the buildup of polyphenylene dendrimers. Around the luminescent core 4, a first-generation (5), a second-generation (6), and a third-generation (7) polyphenylene dendritic envir

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

    Directory of Open Access Journals (Sweden)

    Monika Dabrzalska

    2017-02-01

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

  11. 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].

  12. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-04-15

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

  14. Structural characterization of poly(amino)ester dendrimers and related impurities by electrospray tandem mass spectrometry.

    Science.gov (United States)

    Tintaru, Aura; Monnier, Valérie; Bouillon, Camille; Giordanengo, Rémi; Quéléver, Gilles; Peng, Ling; Charles, Laurence

    2010-08-15

    An acid-terminated poly(amino)ester dendrimer was studied by electrospray ionization tandem mass spectrometry to establish its fragmentation pathways, with the aim of using them to investigate the structure of any defective molecules generated during the dendrimer synthesis. This poly(amino)ester dendrimer could be ionized in both polarities but the most structurally relevant dissociation pathways were found from the deprotonated molecule in negative ion mode. The dissociation pattern of this dendrimer is fully described and supported by accurate mass measurements. The main dissociation reactions of the negatively charged polyacidic dendrimer were shown to consist of (i) the release of carbon dioxide and ethene within a branch, which proceeds as many times as intact neutral branches are available; and (ii) the elimination of an entire dendrimer arm. Monitoring the occurrence of these reactions together with any deviation from these two main routes allowed six major dendritic impurities to be structurally characterized.

  15. Synthesis and self-assembly of PAMAM/PAA Janus dendrimers

    Science.gov (United States)

    Gao, Chunmei; Liu, Mingzhu; Lü, Shaoyu; Zhang, Xinjie; Chen, Yuanmou

    2014-03-01

    Janus dendrimers have two differently functionalized segments which are located on opposite sides. They have many excellent properties and broad application prospects. In this study, poly(amido amine)/poly(acrylic acid) (PAMAM/PAA) Janus dendrimers were prepared by click chemistry. One of the first steps taken was the synthesis of N-Boc-G3.0 PAMAM dendrimers with primary amine groups at the periphery. Second, by amide coupling between propargylic acid and N-Boc-G3.0 PAMAM, PAMAM dendrimers with alkyne were successfully synthesized. After being dissolved in aqueous solutions with different pH, Janus dendrimers spontaneously form flowerlike micellar, Janus particles, and spherical micelles due to primary amino, tertiary amino, and carboxyl groups in the dendrimers. This self-assembly behavior depending on pH changes has a number of potential applications in the field of materials.

  16. Diffusion of Alexa Fluor 488-conjugated dendrimers in rat aortic tissue.

    Science.gov (United States)

    Cho, Brenda S; Roelofs, Karen J; Majoros, Istvan J; Baker, James R; Stanley, James C; Henke, Peter K; Upchurch, Gilbert R

    2006-11-01

    In this study, the distribution of labeled dendrimers in native and aneurysmal rat aortic tissue was examined. Adult male rats underwent infrarenal aorta perfusion with generation 5 (G5) acetylated Alexa Fluor 488-conjugated dendrimers for varying lengths of time. In a second set of experiments, rats underwent aortic elastase perfusion followed by aortic dendrimer perfusion 7 days later. Aortic diameters were measured prior to and postelastase perfusion, and again on the day of harvest. Aortas were harvested 0, 12, or 24 h postperfusion, fixed, and mounted. Native aortas were harvested and viewed as negative controls. Aortic cross-sections were viewed and imaged using confocal microscopy. Dendrimers were quantified (counts/high-powered field). Results were evaluated by repeated measures ANOVA and Student's t-test. We found that in native aortas, dendrimers penetrated the aortic wall in all groups. For all perfusion times, fewer dendrimers were present as time between dendrimer perfusion and aortic harvest increased. Longer perfusion times resulted in increased diffusion of dendrimers throughout the aortic wall. By 24 h, the majority of the dendrimers were through the wall. Dendrimers in aneurysmal aortas, on day 0 postdendrimer perfusion, diffused farther into the aortic wall than controls. In conclusion, this study documents labeled dendrimers delivered intra-arterially to native rat aortas in vivo, and the temporal diffusion of these molecules within the aortic wall. Increasing perfusion time and length of time prior to harvest resulted in continued dendrimer diffusion into the aortic wall. These preliminary data provide a novel mechanism whereby local inhibitory therapy may be delivered locally to aortic tissue.

  17. Adsorption behaviors of Hg(II) on chitosan functionalized by amino-terminated hyperbranched polyamidoamine polymers.

    Science.gov (United States)

    Ma, Fang; Qu, Rongjun; Sun, Changmei; Wang, Chunhua; Ji, Chunnuan; Zhang, Ying; Yin, Ping

    2009-12-30

    The adsorption behaviors of Hg(II) on adsorbents, chitosan functionalized by generation 1.0-3.0 of amino-terminated hyperbranched polyamidoamine polymers (denoted as CTS-1.0, CTS-2.0 and CTS-3.0, respectively), were studied. The optimum pH corresponding to the maximum adsorption capacities was found to be 5.0 for the three adsorbents. The experimental equilibrium data of Hg(II) on the three adsorbents were fitted to the Freundlich and the Langmuir models, and it is found that the Langmuir isotherm was the best fitting model to describe the equilibrium adsorption. The kinetics data indicated that the adsorption process of Hg(II) ions on CTS-1.0, CTS-2.0 and CTS-3.0 were governed by the film diffusion and followed pseudo-second-order rate model. Thermodynamic analysis and FTIR analysis revealed that the adsorption behaviors of Hg(II) ions on the three adsorbents could be considered as spontaneous, endothermic and chemical sorption process, resulting in their higher adsorption capacities at higher temperature.

  18. Sediment washing by EDTA and its reclamation by sodium polyamidoamine-multi dithiocarbamate.

    Science.gov (United States)

    Deng, Tianlin; Zhang, Bingru; Li, Fengting; Jin, Luyao

    2017-02-01

    Sodium polyamidoamine-multi dithiocarbamate (PAMAM-DTC) is a kind of heavy metals capturing agent, containing functional groups of dithiocarbamate that could strongly chelate heavy metals. In this paper, it was applied to precipitate heavy metal ions from meal-EDTA and reclaim EDTA during sediment washing process. The extracting performance of fresh EDTA was studied as a function of EDTA concentration, liquid/sediment (L/S), pH, and extraction time. Then the EDTA effluents were treated with PAMAM-DTC, Na2S and sodium diethyldithiocarbamate (DDTC) to compare their effectiveness on capturing metals from metal-EDTA complexes. Four divalent heavy metals were investigated (Pb, Cd, Cu, Zn). PAMAM-DTC shows much better performance. Pb, Cd and Cu could almost be precipitated completely by PAMAM-DTC under the dosage of 350 mg L(-1), while Zn could be only partly precipitated which may due to its failure in competition with the other three metal ions on chelation with PAMAM-DTC. The reclaimed EDTA was reused in three cycles of sediment washing, and the amount of heavy metals extracted just slightly decreased in each cycle.

  19. 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.

  20. In Silico Characterization of the Binding Affinity of Dendrimers to Penicillin-Binding Proteins (PBPs): Can PBPs be Potential Targets for Antibacterial Dendrimers?

    Science.gov (United States)

    Ahmed, Shaimaa; Vepuri, Suresh B; Ramesh, Muthusamy; Kalhapure, Rahul; Suleman, Nadia; Govender, Thirumala

    2016-04-01

    We have shown that novel silver salts of poly (propyl ether) imine (PETIM) dendron and dendrimers developed in our group exhibit preferential antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus. This led us to examine whether molecular modeling methods could be used to identify the key structural design principles for a bioactive lead molecule, explore the mechanism of binding with biological targets, and explain their preferential antibacterial activity. The current article reports the conformational landscape as well as mechanism of binding of generation 1 PETIM dendron and dendrimers to penicillin-binding proteins (PBPs) in order to understand the antibacterial activity profiles of their silver salts. Molecular dynamics at different simulation protocols and conformational analysis were performed to elaborate on the conformational features of the studied dendrimers, as well as to create the initial structure for further binding studies. The results showed that for all compounds, there were no significant conformational changes due to variation in simulation conditions. Molecular docking calculations were performed to investigate the binding theme between the studied dendrimers and PBPs. Interestingly, in significant accordance with the experimental data, dendron and dendrimer with aliphatic cores were found to show higher activity against S. aureus than the dendrimer with an aromatic core. The latter showed higher activity against MRSA. The findings from this computational and molecular modeling report together with the experimental results serve as a road map toward designing more potent antibacterial dendrimers against resistant bacterial strains.

  1. Sodium sensing in neurons with a dendrimer-based nanoprobe.

    Science.gov (United States)

    Lamy, Christophe M; Sallin, Olivier; Loussert, Céline; Chatton, Jean-Yves

    2012-02-28

    Ion imaging is a powerful methodology to assess fundamental biological processes in live cells. The limited efficiency of some ion-sensing probes and their fast leakage from cells are important restrictions to this approach. In this study, we present a novel strategy based on the use of dendrimer nanoparticles to obtain better intracellular retention of fluorescent probes and perform prolonged fluorescence imaging of intracellular ion dynamics. A new sodium-sensitive nanoprobe was generated by encapsulating a sodium dye in a PAMAM dendrimer nanocontainer. This nanoprobe is very stable and has high sodium sensitivity and selectivity. When loaded in neurons in live brain tissue, it homogenously fills the entire cell volume, including small processes, and stays for long durations, with no detectable alterations of cell functional properties. We demonstrate the suitability of this new sodium nanosensor for monitoring physiological sodium responses such as those occurring during neuronal activity.

  2. 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.

  3. 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].  ……

  4. Hydrogels for osteochondral repair based on photocrosslinkable carbamate dendrimers.

    Science.gov (United States)

    Degoricija, Lovorka; Bansal, Prashant N; Söntjens, Serge H M; Joshi, Neel S; Takahashi, Masaya; Snyder, Brian; Grinstaff, Mark W

    2008-10-01

    First generation, photocrosslinkable dendrimers consisting of natural metabolites (i.e., succinic acid, glycerol, and beta-alanine) and nonimmunogenic poly(ethylene glycol) (PEG) were synthesized divergently in high yields using ester and carbamate forming reactions. Aqueous solutions of these dendrimers were photocrosslinked with an eosin-based photoinitiator to afford hydrogels. The hydrogels displayed a range of mechanical properties based on their structure, generation size, and concentration in solution. All of the hydrogels showed minimal swelling characteristics. The dendrimer solutions were then photocrosslinked in situ in an ex vivo rabbit osteochondral defect (3 mm diameter and 10 mm depth), and the resulting hydrogels were subjected to physiologically relevant dynamic loads. Magnetic resonance imaging (MRI) showed the hydrogels to be fixated in the defect site after the repetitive loading regimen. The ([G1]-PGLBA-MA) 2-PEG hydrogel was chosen for the 6 month pilot in vivo rabbit study because this hydrogel scaffold could be prepared at low polymer weight (10 wt %) and possessed the largest compressive modulus of the 10% formulations, a low swelling ratio, and contained carbamate linkages, which are more hydrolytically stable than the ester linkages. The hydrogel-treated osteochondral defects showed good attachment in the defect site and histological analysis showed the presence of collagen II and glycosaminoglycans (GAGs) in the treated defects. By contrast, the contralateral unfilled defects showed poor healing and negligible GAG or collagen II production. Good mechanical properties, low swelling, good attachment to the defect site, and positive in vivo results illustrate the potential of these dendrimer-based hydrogels as scaffolds for osteochondral defect repair.

  5. 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...

  6. 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

  7. Novel guanidinylated bioresponsive poly(amidoamine)s designed for short hairpin RNA delivery

    Science.gov (United States)

    Yu, Jiankun; Zhang, Jinmin; Xing, Haonan; Sun, Yanping; Yang, Zhen; Yang, Tianzhi; Cai, Cuifang; Zhao, Xiaoyun; Yang, Li; Ding, Pingtian

    2016-01-01

    Two different disulfide (SS)-containing poly(amidoamine) (PAA) polymers were constructed using guanidino (Gua)-containing monomers (ie, arginine [Arg] and agmatine [Agm]) and N,N′-cystamine bisacrylamide (CBA) by Michael-addition polymerization. In order to characterize these two Gua-SS-PAA polymers and investigate their potentials as short hairpin RNA (shRNA)-delivery carriers, pSilencer 4.1-CMV FANCF shRNA was chosen as a model plasmid DNA to form complexes with these two polymers. The Gua-SS-PAAs and plasmid DNA complexes were determined with particle sizes less than 90 nm and positive ζ-potentials under 20 mV at nucleic acid:polymer weight ratios lower than 1:24. Bioresponsive release of plasmid DNA was observed from both newly constructed complexes. Significantly lower cytotoxicity was observed for both polymer complexes compared with polyethylenimine and Lipofectamine 2000, two widely used transfection reagents as reference carriers. Arg-CBA showed higher transfection efficiency and gene-silencing efficiency in MCF7 cells than Agm-CBA and the reference carriers. In addition, the cellular uptake of Arg-CBA in MCF7 cells was found to be higher and faster than Agm-CBA and the reference carriers. Similarly, plasmid DNA transport into the nucleus mediated by Arg-CBA was more than that by Agm-CBA and the reference carriers. The study suggested that guanidine and carboxyl introduced into Gua-SS-PAAs polymers resulted in a better nuclear localization effect, which played a key role in the observed enhancement of transfection efficiency and low cytotoxicity. Overall, two newly synthesized Gua-SS-PAAs polymers demonstrated great potential to be used as shRNA carriers for gene-therapy applications. PMID:27994462

  8. Dendrimer-based organic/inorganic hybrid nanoparticles in biomedical applications

    Science.gov (United States)

    Shen, Mingwu; Shi, Xiangyang

    2010-09-01

    This review reports some recent advances on the synthesis, self-assembly, and biofunctionalization of various dendrimer-based organic/inorganic hybrid nanoparticles (NPs) for various biomedical applications, including but not limited to protein immobilization, gene delivery, and molecular diagnosis. In particular, targeted molecular imaging of cancer using dendrimer-based organic/inorganic hybrid NPs will be introduced in detail.

  9. 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.

  10. Unexpected Temperature Behavior of Polyethylene Glycol Spacers in Copolymer Dendrimers in Chloroform

    Science.gov (United States)

    Markelov, Denis A.; Matveev, Vladimir V.; Ingman, Petri; Nikolaeva, Marianna N.; Penkova, Anastasia V.; Lahderanta, Erkki; Boiko, Natalia I.; Chizhik, Vladimir I.

    2016-04-01

    We have studied copolymer dendrimer structure: carbosilane dendrimers with terminal phenylbenzoate mesogenic groups attached by poly(ethylene) glycol (PEG) spacers. In this system PEG spacers are additional tuning to usual copolymer structure: dendrimer with terminal mesogenic groups. The dendrimer macromolecules were investigated in a dilute chloroform solution by 1H NMR methods (spectra and relaxations). It was found that the PEG layer in G = 5 generations dendrimer is “frozen” at high temperatures (above 260 K), but it unexpectedly becomes “unfrozen” at temperatures below 250 K (i.e., melting when cooling). The transition between these two states occurs within a small temperature range (~10 K). Such a behavior is not observed for smaller dendrimer generations (G = 1 and 3). This effect is likely related to the low critical solution temperature (LCST) of PEG and is caused by dendrimer conformations, in which the PEG group concentration in the layer increases with growing G. We suppose that the unusual behavior of PEG fragments in dendrimers will be interesting for practical applications such as nanocontainers or nanoreactors.

  11. 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

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

    DEFF Research Database (Denmark)

    Gichm, Lise; Christensen, Casper; Boas, Ulrik

    2008-01-01

    Dendrimers are well-defined chemical polymers with a characteristic branching pattern that gives rise to attractive features such as antibacterial and antitumor activities as well as drug delivery properties. In addition, dendrimers can solubilize prion protein aggregates at very low concentratio...

  13. 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.

  14. Electron Transfer in Methylene-Blue-Labeled G3 Dendrimers Tethered to Gold

    DEFF Research Database (Denmark)

    Álvarez-Martos, Isabel; Kartashov, Andrey; Ferapontova, Elena

    2016-01-01

    , and their dependence on the dendrimer surface packing, contribute to both mechanistic pathways. Electrical wiring of horse-radish peroxidase and hexose oxidase by using MB-labeled dendrimers allowed the bioelectrocatalytic reduction of H2O2 and oxidation of glucose by these enzymes. The demonstrated electrical...

  15. 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.

  16. Electron-transfer processes in dendrimers and their implication in biology, catalysis, sensing and nanotechnology

    Science.gov (United States)

    Astruc, Didier

    2012-04-01

    The extraordinary development of the design and synthesis of dendrimers has allowed scientists to locate redox sites at precise positions (core, focal points, branching points, termini, cavities) of these perfectly defined macromolecules, which have generation-controlled sizes and topologies matching those of biomolecules. Redox-dendrimer engineering has led to fine modelling studies of electron-transfer metalloproteins, in which the branches of the dendrimers hinder access to the active site in a manner reminiscent of that of the protein. It has also enabled the construction of remarkable catalysts, sensors and printboards, including by sophisticated design of the interface between redox dendrimers and solid-state devices -- for example by functionalizing electrodes and other surfaces. Electron-transfer processes between dendrimers and a variety of other molecules hold promising applications in diverse areas that range from bio-engineering to sensing, catalysis and energy materials.

  17. 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.

  18. Small-angle x-ray scattering study of polymer structure: Carbosilane dendrimers in hexane solution

    Science.gov (United States)

    Shtykova, E. V.; Feigin, L. A.; Volkov, V. V.; Malakhova, Yu. N.; Streltsov, D. R.; Buzin, A. I.; Chvalun, S. N.; Katarzhanova, E. Yu.; Ignatieva, G. M.; Muzafarov, A. M.

    2016-09-01

    The three-dimensional organization of monodisperse hyper-branched macromolecules of regular structure—carbosilane dendrimers of zero, third, and sixth generations—has been studied by small-angle X-ray scattering (SAXS) in solution. The use of modern methods of SAXS data interpretation, including ab initio modeling, has made it possible to determine the internal architecture of the dendrimers in dependence of the generation number and the number of cyclosiloxane end groups (forming the shell of dendritic macromolecules) and show dendrimers to be spherical. The structural results give grounds to consider carbosilane dendrimers promising objects for forming crystals with subsequent structural analysis and determining their structure with high resolution, as well as for designing new materials to be used in various dendrimer-based technological applications.

  19. Dendrimers as a promising tool in ocular therapeutics: Latest advances and perspectives.

    Science.gov (United States)

    Rodríguez Villanueva, Javier; Navarro, Manuel Guzmán; Rodríguez Villanueva, Laura

    2016-09-10

    Dendrimers have called the attention of scientists in the area of drug and gene delivery over the last two decades for their versatility, complexity and multibranching properties. Some strategies for optimizing drug pharmacokinetics and site-specific targeting using dendrimers have been proposed. Among them, those related to treating and managing ocular diseases are of special interest. Ocular therapies suffer from significant disadvantages, including frequent administration, poor penetration and/or rapid elimination. This review provides an overview of the recent and promising progress in the dendrimers field, focusing on both the anterior and posterior segments of the eye ocular targets, the use of dendrimers as a strategy for overcoming obstacles to the traditional treatment of ocular diseases and an outlook on future directions. Finally, a first approach to ocular safety with dendrimers is intended that accounts for the state-of-the-art science to date.

  20. Polymerization of a divalent/tetravalent metal-storing atom-mimicking dendrimer.

    Science.gov (United States)

    Albrecht, Ken; Hirabayashi, Yuki; Otake, Masaya; Mendori, Shin; Tobari, Yuta; Azuma, Yasuo; Majima, Yutaka; Yamamoto, Kimihisa

    2016-12-01

    The phenylazomethine dendrimer (DPA) has a layer-by-layer electron density gradient that is an analog of the Bohr atom (atom mimicry). In combination with electron pair mimicry, the polymerization of this atom-mimicking dendrimer was achieved. The valency of the mimicked atom was controlled by changing the chemical structure of the dendrimer. By mimicking a divalent atom, a one-dimensional (1D) polymer was obtained, and by using a planar tetravalent atom mimic, a 2D polymer was obtained. These poly(dendrimer) polymers could store Lewis acids (SnCl2) in their unoccupied orbitals, thus indicating that these poly(dendrimer) polymers consist of a series of nanocontainers.

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

    Science.gov (United States)

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

    2014-05-28

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

  2. The first peripherally masked thiol dendrimers: a facile and highly efficient functionalization strategy of polyester dendrimers via one-pot xanthate deprotection/thiol-acrylate Michael addition reactions.

    Science.gov (United States)

    Auty, Sam E R; Andrén, Oliver; Malkoch, Michael; Rannard, Steven P

    2014-06-25

    Introducing multiple reactive functional groups at the periphery of dendrimer materials presents considerable challenges if the functionality is able to self-react. An efficient and facile approach to introducing masked thiols at the surface of polyester dendrimers is presented. One-pot, deprotection/thiol-acrylate Michael addition from the xanthate-functional dendritic substrates (generation zero to two) has been achieved for the first time, with high efficiency demonstrated using three acrylates of varying chemistry and avoiding disulfide formation.

  3. 两亲性树枝状大分子作为药物缓释载体的研究%NANOVEHICLES FOR ANTICANCER DRUG DELIVERY BASED ON AMPHIPHILIC DENDRIMERS

    Institute of Scientific and Technical Information of China (English)

    李金娜; 刘丛丛; 王大伟; 张堃; 杨凤英; 齐林双; 王永健

    2011-01-01

    The amphiphilic dendrimers (PAMAMl-Cag) were prepared by cholic acid and the first generation polyamidoamine (Gl PAMAM) dendrimers. Six cholic acid molecules were linked to one Gl PAMAM which was determined by 'H-NMR and acid-base titration. The modified PAMAM dendrimers self-assembled to form dendritic multimolecular micelles in aqueous solutions, with a hydrodynamic diameter of about 273nm measured by dynamic light scattering. The potential of the amphiphilic dendrimers as an anticancer drug carrier was evaluated using methotrexate (MTX) as a model drug. The results showed that MTX released from PAMAM1-CA6 micelles in different buffer, and its release was sensitive to the surrounding. The release rate of MTX was slow in basic solution (pH=10) while it was obviously increased when the pH of the media was reduced. In addition, the in vitro results demonstrated that the anticancer activity of MTX on human hepatocellular liver carcinoma cells was enhanced after MTX was encapsulated by the micelles in the presence of serum. Therefore, the dendritic multimolecular micelles based on low generation dendrimers may be as stimuli-responsive nanocarriers for drug controlled release.%刺用胆酸对1代聚酰胺-胺树枝状大分子进行修饰,得到两亲性树枝状大分子(PAMAM1-CA6).采用1H-NMR和酸碱滴定法测得每个1代PAMAM分子上共价键连了6个胆酸分子,PAMAM1-CA6在水相中自组装成纳米粒子,粒径约为273nm.以抗癌药物氨甲喋呤为模型考察了此两亲性树枝状大分子对药物的缓释行为.在碱性条件下(pH=10),PAMAM1-CA6对氨甲喋呤的释放较为缓慢;随着溶液pH的降低,药物的释放速率明显加快.说明PAMAM1-CA6对氨甲喋呤的释放具有环境响应性.体外细胞实验的结果表明,PAMAM1-CA6能够显著地提高氨甲喋呤的疗效.因此,这类由低代树枝状大分子制得的材料有望成为新型的药物控释载体.

  4. Novel guanidinylated bioresponsive poly(amidoamines designed for short hairpin RNA delivery

    Directory of Open Access Journals (Sweden)

    Yu J

    2016-12-01

    Full Text Available Jiankun Yu,1 Jinmin Zhang,1 Haonan Xing,1 Yanping Sun,1 Zhen Yang,1 Tianzhi Yang,2 Cuifang Cai,1 Xiaoyun Zhao,3 Li Yang,1 Pingtian Ding1 1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China; 2Department of Basic Pharmaceutical Sciences, School of Pharmacy, Husson University, Bangor, ME, USA; 3Department of Microbiology and Cell Biology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China Abstract: Two different disulfide (SS-containing poly(amidoamine (PAA polymers were constructed using guanidino (Gua-containing monomers (ie, arginine [Arg] and agmatine [Agm] and N,N'-cystamine bisacrylamide (CBA by Michael-addition polymerization. In order to characterize these two Gua-SS-PAA polymers and investigate their potentials as short hairpin RNA (shRNA-delivery carriers, pSilencer 4.1-CMV FANCF shRNA was chosen as a model plasmid DNA to form complexes with these two polymers. The Gua-SS-PAAs and plasmid DNA complexes were determined with particle sizes less than 90 nm and positive ζ-potentials under 20 mV at nucleic acid:polymer weight ratios lower than 1:24. Bioresponsive release of plasmid DNA was observed from both newly constructed complexes. Significantly lower cytotoxicity was observed for both polymer complexes compared with polyethylenimine and Lipofectamine 2000, two widely used transfection reagents as reference carriers. Arg-CBA showed higher transfection efficiency and gene-silencing efficiency in MCF7 cells than Agm-CBA and the reference carriers. In addition, the cellular uptake of Arg-CBA in MCF7 cells was found to be higher and faster than Agm-CBA and the reference carriers. Similarly, plasmid DNA transport into the nucleus mediated by Arg-CBA was more than that by Agm-CBA and the reference carriers. The study suggested that guanidine and carboxyl introduced into Gua-SS-PAAs polymers resulted in a better nuclear localization effect, which played a key role in the

  5. Carboxymethyl chitosan-poly(amidoamine) dendrimer core-shell nanoparticles for intracellular lysozyme delivery.

    Science.gov (United States)

    Zhang, Xiaoyang; Zhao, Jun; Wen, Yan; Zhu, Chuanshun; Yang, Jun; Yao, Fanglian

    2013-11-06

    Intracellular delivery of native, active proteins is challenging due to the fragility of most proteins. Herein, a novel polymer/protein polyion complex (PIC) nanoparticle with core-shell structure was prepared. Carboxymethyl chitosan-grafted-terminal carboxyl group-poly(amidoamine) (CM-chitosan-PAMAM) dendrimers were synthesized by amidation and saponification reactions. (1)H NMR was used to characterize CM-chitosan-PAMAM dendrimers. The TEM images and results of lysozyme loading efficiency indicated that CM-chitosan-PAMAM dendrimers could self-assemble into core-shell nanoparticles, and lysozyme was efficiently encapsulated inside the core of CM-chitosan-PAMAM dendrimer nanoparticles. Activity of lysozyme was completely inhibited by CM-chitosan-PAMAM Dendrimers at physiological pH, whereas it was released into the medium and exhibited a significant enzymatic activity in an acidic intracellular environment. Moreover, the CM-chitosan-PAMAM dendrimer nanoparticles did not exhibit significant cytotoxicity in the range of concentrations below 3.16 mg/ml. The results indicated that these CM-chitosan-PAMAM dendrimers have excellent properties as highly potent and non-toxic intracellular protein carriers, which would create opportunities for novel applications in protein delivery.

  6. 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.

  7. 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.

  8. Rational design of dendrimer/lipid nanoassemblies in drug delivery for cancer chemotherapy

    Science.gov (United States)

    Sun, Qihang

    Nanocarriers can minimize the side effects and improve therapeutic efficacy of anticancer drugs. Although some success has been achieved via active or passive drug delivery to tumor cells, the known nanocarriers are far from satisfying therapeutic efficacy expectations. This is because they usually fail in one of the four crucial requirements, that is, to retain drug in blood circulation but release it reliably in tumor cells and to be stealthy in transport in circulation and tumor tissue but sticky upon arrival at the tumor cell. Therefore, the goal of this work is to fabricate nanoassemblies of dendrimers and lipids to address all these challenges. Particularly, nanoassemblies designed and prepared in this work are illustrated to improve the tumor tissue penetration. Examples of dendrimers synthesized in this work are water-insoluble, pH-dependent water-insoluble and water-soluble biodegradable polyester dendrimers. These dendrimers are shown to be encapsulated by commonly used fusogenic and long-circulating lipids to form reliable nanoassemblies. The dendrimer/lipid nanocarriers are used to demonstrate a cascade drug delivery. They are expected to be stable in circulation, due to their appropriately large size, but to release the drug-loaded dendrimers in tumor tissue. The released dendrimers carrying drugs are much smaller and hence expected to have a much deeper penetration throughout the tumor tissue.

  9. Development of TREN dendrimers over mesoporous SBA-15 for CO 2 adsorption

    Science.gov (United States)

    Bhagiyalakshmi, Margandan; Park, Sang Do; Cha, Wang Seog; Jang, Hyun Tae

    2010-09-01

    Mesoporous SBA-15 was synthesized using rice husk ash (RHA) as the silica source and their defective Si-OH groups were grafted with tris(2-aminoethyl) amine (TREN) dendrimers generation through step-wise growth technique. The X-ray diffraction (XRD) and nitrogen adsorption/desorption results of parent SBA-15 obtained from RHA, suggests its resemblance with SBA-15 synthesized using conventional silica sources. Furthermore, the nitrogen adsorption/desorption results of SBA-15/TREN dendrimer generations (G1-G3) illustrates the growth of dendrimer inside the mesopores of SBA-15 and their CO 2 adsorption capacity was determined at 25 °C. The maximum CO 2 adsorption capacity of 5-6 and 7-8 wt% over second and third dendrimer generation was observed which is discernibly higher than the reported melamine and PAMAM dendrimers. The experimental CO 2 adsorption capacity was found to be less than theoretically calculated CO 2 adsorption capacity due to inter and intra molecular amidation as result of steric hindrance during the dendrimer growth. These SBA-15/TREN dendrimer generations also exhibit thermal stability up to 350 °C and CO 2 adsorption capacity remains unaltered upon seven consecutive runs.

  10. Interaction of a patterned amphiphilic polyphenylene dendrimer with a lipid monolayer: electrostatic interactions dominate.

    Science.gov (United States)

    Okuno, Masanari; Mezger, Markus; Stangenberg, René; Baumgarten, Martin; Müllen, Klaus; Bonn, Mischa; Backus, Ellen H G

    2015-02-17

    Dendrimeric macromolecules with defined shape and size are promising candidates for delivering drug or DNA molecules into cells. In this work we study the influence of an amphiphilic polyphenylene dendrimer on a model cell membrane consisting of a condensed 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid monolayer. A small surface pressure decrease is observed when the dendrimer solution is injected into the aqueous phase below the monolayer. X-ray reflectivity measurements show that the surface monolayer remains intact. The molecular-scale picture is obtained with sum-frequency generation spectroscopy. With this technique, we observe that the tails of the surfactant molecules become less ordered upon interaction with the amphiphilic polyphenylene dendrimer. In contrast, the water molecules below the DPPC layer become more ordered. Our observations suggest that electrostatic interactions between the negative charge of the dendrimer and the positively charged part of the DPPC headgroup keep the dendrimer located below the headgroup. No evidence of dendrimer insertion into the membrane has been observed. Apparently before entering the cell membrane the dendrimer can stick at the hydrophilic part of the lipids.

  11. Synthesis, Radiolabeling, and In Vivo Imaging of PEGylated High-Generation Polyester Dendrimers.

    Science.gov (United States)

    McNelles, Stuart A; Knight, Spencer D; Janzen, Nancy; Valliant, John F; Adronov, Alex

    2015-09-14

    A fifth generation aliphatic polyester dendrimer was functionalized with vinyl groups at the periphery and a dipicolylamine Tc(I) chelate at the core. This structure was PEGylated with three different molecular weight mPEGs (mPEG160, mPEG350, and mPEG750) using thiol-ene click chemistry. The size of the resulting macromolecules was evaluated using dynamic light scattering, and it was found that the dendrimer functionalized with mPEG750 was molecularly dispersed in water, exhibiting a hydrodynamic diameter of 9.2 ± 2.1 nm. This PEGylated dendrimer was subsequently radiolabeled using [(99m)Tc(CO)3(H2O)3](+) and purified to high (>99%) radiochemical purity. Imaging studies were initially performed on healthy rats to allow comparison to previous Tc-labeled dendrimers and then on xenograft murine tumor models, which collectively showed that the dendrimers circulated in the blood for an extended period of time (up to 24 h). Furthermore, the radiolabeled dendrimer accumulated in H520 xenograft tumors, which could be visualized by single-photon emission computed tomography (SPECT). The reported PEGylated aliphatic polyester dendrimers represent a new platform for developing tumor-targeted molecular imaging probes and therapeutics.

  12. "Lego" chemistry for the straightforward synthesis of dendrimers.

    Science.gov (United States)

    Maraval, Valérie; Pyzowski, Jaroslaw; Caminade, Anne-Marie; Majoral, Jean-Pierre

    2003-07-25

    A new straightforward method of synthesis of dendrimers, using two branched monomers (CA(2) and DB(2)), is described. Each generation is obtained in a single quantitative step, with only N(2) or H(2)O as byproducts; generation 4 is obtained in only four steps. The end groups are alternatively phosphines and hydrazines; their versatile reactivity is illustrated by the reaction of generation 4 with a branched CD(5) monomer, which increases the number of end groups in a single step from 48 to 250.

  13. Study of the complexation of oxacillin in 1-(4-Carbomethoxypyrrolidone)-terminated PAMAM dendrimers

    DEFF Research Database (Denmark)

    Hansen, Jon Stefan; Ficker, Mario; Petersen, Johannes Fabritius

    2013-01-01

    The complexation of oxacillin to three generations of 1-(4-carbomethoxypyrrolidone)-terminated PAMAM dendrimers was studied with NMR in CD3OD and CDCl3. The stochiometries, which were determined from Job plots, were found to be both solvent- and generation-dependent. The dissociation constants (Kd......) and Gibbs energies for complexation of oxacillin into the 1-(4-carbomethoxypyrrolidone)-terminated PAMAM dendrimer hosts were determined by (1)H NMR titrations and showed weaker binding of oxacillin upon increasing the size (generation) of the dendrimer....

  14. Enhancement of muramyldipeptide (MDP) immunostimulatory activity by controlled multimerization on dendrimers.

    Science.gov (United States)

    Sorensen, Nanna S; Boas, Ulrik; Heegaard, Peter M H

    2011-11-10

    Peptidoglycan is a widespread bacterial PAMP molecule and a powerful initiator of innate immune responses. It consists of repeating units of MDP, which as a monomer is only weakly immunostimulatory. Here, MDP-coupled dendrimers were prepared and investigated for stimulation of pig blood mononuclear cells. Compared to monomeric MDP, MDP-dendrimers induced a markedly enhanced production of IL-12 p40, IL-1β and IL-6 and completely down-regulated surface expression of B7 and MHC class II. These results suggest a possible novel strategy based on controlled multimerization of minimal PAMP motifs on dendrimers for preparing molecularly defined immunostimulators with predictable bioactivities.

  15. Interactions of dendrimers with biological drug targets: reality or mystery - a gap in drug delivery and development research.

    Science.gov (United States)

    Ahmed, Shaimaa; Vepuri, Suresh B; Kalhapure, Rahul S; Govender, Thirumala

    2016-07-21

    Dendrimers have emerged as novel and efficient materials that can be used as therapeutic agents/drugs or as drug delivery carriers to enhance therapeutic outcomes. Molecular dendrimer interactions are central to their applications and realising their potential. The molecular interactions of dendrimers with drugs or other materials in drug delivery systems or drug conjugates have been extensively reported in the literature. However, despite the growing application of dendrimers as biologically active materials, research focusing on the mechanistic analysis of dendrimer interactions with therapeutic biological targets is currently lacking in the literature. This comprehensive review on dendrimers over the last 15 years therefore attempts to identify the reasons behind the apparent lack of dendrimer-receptor research and proposes approaches to address this issue. The structure, hierarchy and applications of dendrimers are briefly highlighted, followed by a review of their various applications, specifically as biologically active materials, with a focus on their interactions at the target site. It concludes with a technical guide to assist researchers on how to employ various molecular modelling and computational approaches for research on dendrimer interactions with biological targets at a molecular level. This review highlights the impact of a mechanistic analysis of dendrimer interactions on a molecular level, serves to guide and optimise their discovery as medicinal agents, and hopes to stimulate multidisciplinary research between scientific, experimental and molecular modelling research teams.

  16. Click chemistry with polymers, dendrimers, and hydrogels for drug delivery.

    Science.gov (United States)

    Lallana, Enrique; Fernandez-Trillo, Francisco; Sousa-Herves, Ana; Riguera, Ricardo; Fernandez-Megia, Eduardo

    2012-04-01

    During the last decades, great efforts have been devoted to design polymers for reducing the toxicity, increasing the absorption, and improving the release profile of drugs. Advantage has been also taken from the inherent multivalency of polymers and dendrimers for the incorporation of diverse functional molecules of interest in targeting and diagnosis. In addition, polymeric hydrogels with the ability to encapsulate drugs and cells have been developed for drug delivery and tissue engineering applications. In the long road to this successful story, pharmaceutical sciences have been accompanied by parallel advances in synthetic methodologies allowing the preparation of precise polymeric materials with enhanced properties. In this context, the introduction of the click concept by Sharpless and coworkers in 2001 focusing the attention on modularity and orthogonality has greatly benefited polymer synthesis, an area where reaction efficiency and product purity are significantly challenged. The purpose of this Expert Review is to discuss the impact of click chemistry in the preparation and functionalization of polymers, dendrimers, and hydrogels of interest in drug delivery.

  17. Organometallic Silicon-Containing Dendrimers and Their Electrochemical Applications

    Science.gov (United States)

    Cuadrado, Isabel

    Dendrimers constitute a unique class of macromolecular architectures that differs from all other synthetic macromolecules in its perfectly branched topology, which is constructed from a multifunctional central core and expands to the periphery that becomes denser with increasing generation number (see Chapter 1) [1-5]. Since the pioneering works published in the late 1970s and the mid-1980s [6-8], the design and synthesis of these tree-like, well-defined molecules, which exhibit a unique combination of chemical and physical properties, is a field which has sustained dramatic growth and has generated enthusiastic studies at the frontiers of organic, inorganic, supramolecular and polymer chemistry, and more recently in the fields of nanoscience, biotechnology and medicine [1-5, 9, 10]. Whereas the initial interest in dendrimers was focused on the synthetic and structural characterization challenges that pose their fractal geometries, nanometer sizes and monodisperse nature, in the last decade the emphasis has been placed mainly on modification of the properties of dendritic molecules by their functionalization

  18. 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.

  19. 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.

  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.

  1. Synthesis of Dendrimer Containing Dialkylated-fluorene Unit as a Core Chromophore via Click Chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Han, Seung Choul; Lee, Jae Wook [Dong-A University, Busan (Korea, Republic of); Jin, Sung Ho [Pusan National University, Busan (Korea, Republic of)

    2012-01-15

    The convergent synthetic strategy for the emissive dendrimers having the chromophore at core via the coppercatalyzed 1,3-dipolar cycloaddition reaction between alkyne and azide was described. 2,7-Diazido-9,9-dioctyl- 9H-fluorene, designed to serve as the core in dendrimer, was stitched with the alkyne-functionalized Frechettype and PAMAM dendrons by the click chemistry leading to the formation of the corresponding fluorescent dendrimers in high yields. The preliminary photoluminescence studies indicated that 2,7-diazido-9,9-dioctyl- 9H-fluorene showed no fluorescence due to the quenching effect from the electron-rich α-nitrogen of the azido group but the dendrimers fluoresced due to the elimination of the quenching through the formation of the triazole ring.

  2. 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].

  3. Phosphorus-Based Dendrimer ABP Treats Neuroinflammation by Promoting IL-10-Producing CD4(+) T Cells.

    Science.gov (United States)

    Hayder, Myriam; Varilh, Marjorie; Turrin, Cédric-Olivier; Saoudi, Abdelhadi; Caminade, Anne-Marie; Poupot, Rémy; Liblau, Roland S

    2015-11-09

    Dendrimers are polyfunctional nano-objects of perfectly defined structure that can provide innovative alternatives for the treatment of chronic inflammatory diseases, including multiple sclerosis (MS). To investigate the efficiency of a recently described amino-bis(methylene phosphonate)-capped ABP dendrimer as a potential drug candidate for MS, we used the classical mouse model of MOG35-55-induced experimental autoimmune encephalomyelitis (EAE). Our study provides evidence that the ABP dendrimer prevents the development of EAE and inhibits the progression of established disease with a comparable therapeutic benefit as the approved treatment Fingolimod. We also show that the ABP dendrimer redirects the pathogenic myelin-specific CD4(+) T cell response toward IL-10 production.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. Dendrimer nanoscaffolds for potential theranostics of prostate cancer with a focus on radiochemistry.

    Science.gov (United States)

    Lo, Su-Tang; Kumar, Amit; Hsieh, Jer-Tsong; Sun, Xiankai

    2013-03-04

    Dendrimers are a class of structurally defined macromolecules featured with a central core, a low-density interior formed by repetitive branching units, and a high-density exterior terminated with surface functional groups. In contrast to their polymeric counterparts, dendrimers are nanosized and symmetrically shaped, which can be reproducibly synthesized on a large scale with monodispersity. These unique features have made dendrimers of increasing interest for drug delivery and other biomedical applications as nanoscaffold systems. Intended to address the potential use of dendrimers for the development of theranostic agents, which combines therapeutics and diagnostics in a single entity for personalized medicine, this review focuses on the reported methodologies of using dendrimer nanoscaffolds for targeted imaging and therapy of prostate cancer. Of particular interest, relevant chemistry strategies are discussed due to their important roles in the design and synthesis of diagnostic and therapeutic dendrimer-based nanoconjugates and potential theranostic agents, targeted or nontargeted. Given the developing status of nanoscaffolded theranostics, major challenges and potential hurdles are discussed along with the examples representing current advances.

  11. 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.

  12. Monolayers of poly(amido amine) dendrimers on mica - In situ streaming potential measurements.

    Science.gov (United States)

    Michna, Aneta; Adamczyk, Zbigniew; Sofińska, Kamila; Matusik, Katarzyna

    2017-01-01

    The deposition of poly(amido amine) dendrimers on mica at various pHs was studied by the atomic force microscopy (AFM) and in situ streaming potential measurements. Bulk characteristics of dendrimers were acquired by using the dynamic light scattering (DLS) and the laser Doppler velocimetry (LDV). The hydrodynamic radius derived from DLS measurements was 5.2nm for the ionic strength of 10(-2)M and pH range 4-10. The electrophoretic mobility, the zeta potential and the number of electrokinetic charges per molecule were derived as a function of pH from the LDV measurements. It was revealed that the dendrimers are positively charged for pH up to 10. This promoted their deposition on negatively charged mica substrate whose kinetics was quantitatively evaluated by direct AFM imaging and streaming potential measurements interpreted in terms of the electrokinetic model. The desorption kinetics of dendrimers under flowing conditions from monolayers of various coverage was also studied. It was revealed that dendrimer deposition was partially reversible for pH above 5.8. The acid-base properties of the dendrimer monolayers deposited on mica were characterized.

  13. Principal physicochemical methods used to characterize dendrimer molecule complexes used as genetic therapy agents, nanovaccines or drug carriers.

    Science.gov (United States)

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

    2017-02-20

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

  14. Controlled doping by self-assembled dendrimer-like macromolecules

    Science.gov (United States)

    Wu, Haigang; Guan, Bin; Sun, Yingri; Zhu, Yiping; Dan, Yaping

    2017-02-01

    Doping via self-assembled macromolecules might offer a solution for developing single atom electronics by precisely placing individual dopants at arbitrary location to meet the requirement for circuit design. Here we synthesize dendrimer-like polyglycerol macromolecules with each carrying one phosphorus atom in the core. The macromolecules are immobilized by the coupling reagent onto silicon surfaces that are pre-modified with a monolayer of undecylenic acid. Nuclear magnetic resonance (NMR) and X-ray photoelectron spectroscopy (XPS) are employed to characterize the synthesized macromolecules and the modified silicon surfaces, respectively. After rapid thermal annealing, the phosphorus atoms carried by the macromolecules diffuse into the silicon substrate, forming dopants at a concentration of 1017 cm‑3. Low-temperature Hall effect measurements reveal that the ionization process is rather complicated. Unlike the widely reported simple ionization of phosphorus dopants, nitrogen and carbon are also involved in the electronic activities in the monolayer doped silicon.

  15. 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.

  16. 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.

  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. Divalent folate modification on PEG: an effective strategy for improving the cellular uptake and targetability of PEGylated polyamidoamine-polyethylenimine copolymer.

    Science.gov (United States)

    Cao, Duanwen; Tian, Shouqin; Huang, Huan; Chen, Jianhai; Pan, Shirong

    2015-01-05

    The stability and targeting ability of nanocarrier gene delivery systems are necessary conditions to ensure the good therapeutic effect and low nonspecific toxicity of cancer treatment. Poly(ethylene glycol) (PEG) has been widely applied for improving stability and as a spacer for linking ligands and nanocarriers to improve targetability. However, the cellular uptake and endosomal escape capacity of nanocarriers has been seriously harmed due to the introduction of PEG. In the present study, we synthesized a new gene delivery vector by coupling divalent folate-PEG (PEG3.4k-FA2) onto polyamidoamine-polyethylenimine (PME) copolymer (PME-(PEG3.4k-FA2)1.72). Both PEG and monovalent folate-PEG (PEG3.4k-FA1) modified PME were prepared as control polymers, which were named as PME-(PEG3.5k)1.69 and PME-(PEG3.4k-FA1)1.66, respectively. PME-(PEG3.4k-FA2)1.72 exhibited strong DNA condensation capacity like parent polymer PME which was not significantly influenced by PEG. PME-(PEG3.4k-FA2)1.72/DNA complexes at N/P = 10 had a diameter ∼143 nm and zeta potential ∼13 mV and showed the lowest cytotoxicity and hemolysis and the highest transfection efficiency among all tested polymers. In folate receptor positive (FR-positive) cells, the cellular uptake and transfection efficiency were increased with the increase in the number of folates coupled on PEG; the order was PME-(PEG3.4k-FA2)1.72 > PME-(PEG3.4k-FA1)1.66 > PME-(PEG3.5k)1.69. Folate competition assays showed that PME-(PEG3.4k-FA2)1.72 complexes had stronger targeting ability than PME-(PEG3.5k)1.69 and PME-(PEG3.4k-FA1)1.66 complexes due to their higher folate density per PEG molecule. Cellular uptake mechanism study showed that the folate density on PEG could change the endocytosis pathway of PME-(PEG3.5k)1.69 from clathrin-mediated endocytosis to caveolae-mediated endocytosis, leading to less lysosomal degradation. Distribution and uptake in 3D multicellular spheroid assays showed that divalent folate could offer PME

  20. A PEM fuel cell based on electrocatalyst and membrane materials modified by PANAM dendrimers

    Energy Technology Data Exchange (ETDEWEB)

    Ledesma-Garcia, J.; Chapman, T.W.; Godinez, L.A. [Centro de Investigacion y Desarrollo Tecnologico en Electroquimica, Queretaro (Mexico)

    2008-10-15

    Due to its high energy conversion efficiency and low emission of pollutants, fuel-cell technology has been generally recognized as a key twenty-first century energy source. For polymer electrolyte membrane fuel cells (PEMFC), it has been found that platinum and its alloys exhibit the best electrocatalytic activity for oxygen reduction. The highest electrocatalytic activity of platinum and its alloys can be achieved when the particles are produced in the nanometer range. In this context, organic molecules have been adopted as templates to control the size of metal nanoparticles. Dendrimers, in particular, have shown promising properties for this application, and strategies that include direct adsorption, electrostatic attachment and covalent bonding have been developed for connecting metal-bearing dendrimers to conducting substrates. This paper reported on the preliminary results of a study that involved the construction and testing of a hydrogen-oxygen PEM fuel cell based on carbon-fiber-paper electrodes coated with hydroxyl-terminated dendrimers that encapsulated nanoparticles of platinum. This prototype cell also employed an ion exchange membrane comprising a cellulose acetate filter functionalized with proton-exchanging dendrimers. A proton-exchange membrane was prepared by binding duplex amine-carboxylate dendrimers to a cellulose-acetate support. With these dendrimer-based materials, a hydrogen-oxygen fuel cell was assembled and the performance compared with cells prepared with Nafion-based membranes. The voltage-current profiles and the power-density curves from the new cell provide encouragement to continue work with these dendrimer-modified materials. The paper discussed the experimental methods, with particular reference to materials; electrode preparation and characterization; proton-exchange membrane preparation; and PEM fuel-cell assembly and testing. It was concluded that the use of the dendritic macromolecules as supports for the nanoparticulate

  1. 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

  2. Poly(dendrimers) with phosphorescent iridium(III) complex-based side chains prepared via ring-opening metathesis polymerization

    NARCIS (Netherlands)

    Lai, W.-Y.; Balfour, M.N.; Levell, J.W.; Bansal, A.K.; Burn, P.L.; Lo, S.-C.; Samuel, I.D.W.

    2012-01-01

    Phosphorescent poly(dendrimers) with a norbornene-derived backbone have been synthesized using ring-opening metathesis polymerization with the Grubbs III catalyst. The dendrimers are comprised of a heteroleptic iridium(III) complex core with two 2-phenylpyridyl ligands and a phenyltriazolyl ligand,

  3. 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.

  4. Zn (II and Cu (II Halide Complexes of Poly(propylene amine Dendrimer Analysed by Infrared and Raman Spectroscopies

    Directory of Open Access Journals (Sweden)

    Ivo Grabchev

    2013-01-01

    Full Text Available Two nondestructive and complementary spectral methods as infrared and Raman spectroscopies have been used for characterizations of poly(propylene amine dendrimers comprising 1,8-naphthalimide units in the dendrimer periphery and their metal complexes with Cu2+ at Zn2+ ions.

  5. Poly(amidoamine Hydrogels as Scaffolds for Cell Culturing and Conduits for Peripheral Nerve Regeneration

    Directory of Open Access Journals (Sweden)

    Fabio Fenili

    2011-01-01

    Full Text Available Biodegradable and biocompatible poly(amidoamine-(PAA- based hydrogels have been considered for different tissue engineering applications. First-generation AGMA1 hydrogels, amphoteric but prevailing cationic hydrogels containing carboxylic and guanidine groups as side substituents, show satisfactory results in terms of adhesion and proliferation properties towards different cell lines. Unfortunately, these hydrogels are very swellable materials, breakable on handling, and have been found inadequate for other applications. To overcome this problem, second-generation AGMA1 hydrogels have been prepared adopting a new synthetic method. These new hydrogels exhibit good biological properties in vitro with satisfactory mechanical characteristics. They are obtained in different forms and shapes and successfully tested in vivo for the regeneration of peripheral nerves. This paper reports on our recent efforts in the use of first-and second-generation PAA hydrogels as substrates for cell culturing and tubular scaffold for peripheral nerve regeneration.

  6. Facile and Efficient Synthesis of Carbosiloxane Dendrimers via Orthogonal Click Chemistry Between Thiol and Ene.

    Science.gov (United States)

    Zhang, Zhida; Feng, Shengyu; Zhang, Jie

    2016-02-01

    A combination of a thiol-Michael addition reaction and a free radical mediated thiol-ene reaction is employed as a facile and efficient approach to carbosiloxane dendrimer synthesis. For the first time, carbosiloxane dendrimers are constructed rapidly by an orthogonal click strategy without protection/deprotection procedures. The chemoselectivity of these two thiol-ene click reactions leads to a design of a new monomer containing both electron-deficient carbon-carbon double bonds and unconjugated carbon-carbon double bonds. Siloxane bonds are introduced as the linker between these two kinds of carbon-carbon double bonds. Starting from a bifunctional thiol core, the dendrimers are constructed by iterative thiol-ene click reactions under different but both mild reaction conditions. After simple purification steps the fifth dendrimer with 54 peripheral functional groups is obtained with an excellent overall yield in a single day. Furthermore, a strong blue glow is observed when the dendrimer is excited by a UV lamp.

  7. Role of PAMAM-OH dendrimers against the fibrillation pathway of biomolecules.

    Science.gov (United States)

    Sekar, Gajalakshmi; Florance, Ida; Sivakumar, A; Mukherjee, Amitava; Chandrasekaran, Natarajan

    2016-12-01

    The binding behavior of nanoparticle with proteins determines its biocompatibility. This study reports the interaction of ten different biomolecules (proteins-BSA, HSA, haemoglobin, gamma globulin, transferrin and enzymes-hog and bacillus amylase, lysozyme from chicken and human and laccases from Tramates versicolor) with a surface group hydroxylated Poly AMido AMide dendrimer (PAMAM) of generation 5. The study has utilized various spectroscopic methods like UV-vis spectroscopy, Fluorescence emission, Synchronous, 3-D spectroscopy and Circular Dichroism to detect the binding induced structural changes in biomolecules that occur upon interaction with mounting concentration of the dendrimers. Aggregation of proteins results in the formation of amyloid fibrils causing several human diseases. In this study, fibrillar samples of all ten biomolecules formed in the absence and the presence of dendrimers were investigated with Congo Red absorbance and ThT Assay to detect fibril formation, Trp Emission and 3-D scan to evaluate the effect of fibrillation on aromatic environment of biomolecules, and CD spectroscopy to measure the conformational changes in a quantitative manner. These assays have generated useful information on the role of dendrimers in amyloid fibril formation of biomolecules. The outcomes of the study remain valuable in evaluating the biological safety of PAMAM-OH dendrimers for their biomedical application in vivo.

  8. A multiscale scheme for the simulation of conformational and solution properties of different dendrimer molecules.

    Science.gov (United States)

    Del Río Echenique, Gustavo; Rodríguez Schmidt, Ricardo; Freire, Juan J; Hernández Cifre, José G; García de la Torre, José

    2009-06-24

    We propose a multiscale protocol for the simulation of conformation and dynamics of dendrimer molecules in dilute solution. Conformational properties (radius of gyration, mass distribution, and scattering intensities) and overall hydrodynamic properties (translational diffusion and intrinsic viscosity) are predicted by means of a very simple coarse-grained bead-and-spring model, whose parameters are not adjusted against experimental properties, but rather they are obtained from previous, atomic-level simulations which are also quite simple, performed with small fragments and Langevin dynamics simulation. The scheme is described and applied systematically to four different dendrimer molecules with up to seven generations. The predictive capability of this scheme is tested by comparison with experimental data. It is found that the predicted geometric and hydrodynamic radii of the dendrimer molecules are in agreement (typical error is about 4%) with a large set experimental values of the four dendrimers with various numbers of generations. Agreement with some X-ray scattering experimental intensities also confirms the good prediction of the internal structure. This scheme is easily extendable to study more complex molecules (e.g., functionalized dendrimers) and to simulate internal dynamics.

  9. 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.

  10. 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.

  11. Reprogramming fibroblasts to pluripotency using arginine-terminated polyamidoamine nanoparticles based non-viral gene delivery system

    Science.gov (United States)

    Zhu, Kai; Li, Jun; Lai, Hao; Yang, Cheng; Guo, Changfa; Wang, Chunsheng

    2014-01-01

    Induced pluripotent stem cells (iPSCs) have attracted keen interest in regenerative medicine. The generation of iPSCs from somatic cells can be achieved by the delivery of defined transcription factor (Oct4, Sox2, Klf4, and c-Myc[OSKM]). However, most instances of iPSC-generation have been achieved by potentially harmful genome-integrating viral vectors. Here we report the generation of iPSCs from mouse embryonic fibroblasts (MEFs) using arginine-terminated generation 4 polyamidoamine (G4Arg) nanoparticles as a nonviral transfection vector for the delivery of a single plasmid construct carrying OSKM (pOSKM). Our results showed that G4Arg nanoparticles delivered pOSKM into MEFs at a significantly higher transfection efficiency than did conventional transfection reagents. After serial transfections of pOSKM-encapsulated G4Arg nanoparticles, we successfully generated iPSCs from MEFs. Our study demonstrates that G4Arg nanoparticles may be a promising candidate for generating of virus-free iPSCs that have great potential for clinical application. PMID:25540584

  12. Reprogramming fibroblasts to pluripotency using arginine-terminated polyamidoamine nanoparticles based non-viral gene delivery system

    Directory of Open Access Journals (Sweden)

    Zhu K

    2014-12-01

    Full Text Available Kai Zhu,1,2,* Jun Li,1,2,* Hao Lai,1,2 Cheng Yang,1,2 Changfa Guo,1,2 Chunsheng Wang1,2 1Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, 2Shanghai Institute of Cardiovascular Disease, Shanghai, People’s Republic of China *These authors contributed equally to this article Abstract: Induced pluripotent stem cells (iPSCs have attracted keen interest in regenerative medicine. The generation of iPSCs from somatic cells can be achieved by the delivery of defined transcription factor (Oct4, Sox2, Klf4, and c-Myc[OSKM]. However, most instances of iPSC-generation have been achieved by potentially harmful genome-integrating viral vectors. Here we report the generation of iPSCs from mouse embryonic fibroblasts (MEFs using arginine-terminated generation 4 polyamidoamine (G4Arg nanoparticles as a nonviral transfection vector for the delivery of a single plasmid construct carrying OSKM (pOSKM. Our results showed that G4Arg nanoparticles delivered pOSKM into MEFs at a significantly higher transfection efficiency than did conventional transfection reagents. After serial transfections of pOSKM-encapsulated G4Arg nanoparticles, we successfully generated iPSCs from MEFs. Our study demonstrates that G4Arg nanoparticles may be a promising candidate for generating of virus-free iPSCs that have great potential for clinical application. Keywords: mouse embryonic fibroblasts, induced pluripotent stem cells

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Characterization and evaluation of amphotericin B loaded MDP conjugated poly(propylene imine) dendrimers.

    Science.gov (United States)

    Jain, Keerti; Verma, Ashwni Kumar; Mishra, Prabhat Ranjan; Jain, Narendra Kumar

    2015-04-01

    This paper describes a novel strategy for targeted delivery of amphotericin B (AmB) to macrophages with muramyl dipeptide (MDP) conjugated multimeric poly(propyleneimine) (PPI) dendrimers. Synergistic antiparasitic activity due to immunostimulation by multimeric presentation of MDP on dendrimers was anticipated. MDP conjugated 5.0G PPI (MdPPI) dendrimers were synthesized and characterized. Therapeutic activity and toxicity of dendrimeric formulation of AmB (MdPPIA) were compared with marketed formulations of AmB. Highly significant (PMDP conjugated dendrimeric formulation of AmB as a promising immunostimulant targeted drug delivery system and a safer alternative to marketed formulations. From the clinical editor: Parasitic infections remain a significant issue in the clinical setting. The authors in this article studied the use of ligand anchored dendrimeric formulation of Amphotericin B to target infected macrophages and showed reduced toxicity, high anti-leishmanial activity. This may add another treatment option to available formulations in the future.

  18. Facile synthesis of polyester dendrimers from sequential click coupling of asymmetrical monomers.

    Science.gov (United States)

    Ma, Xinpeng; Tang, Jianbin; Shen, Youqing; Fan, Maohong; Tang, Huadong; Radosz, Maciej

    2009-10-21

    Polyester dendrimers are attractive for in vivo delivery of bioactive molecules due to their biodegradability, but their synthesis generally requires multistep reactions with intensive purifications. A highly efficient approach to the synthesis of dendrimers by simply "sticking" generation by generation together is achieved by combining kinetic or mechanistic chemoselectivity with click reactions between the monomers. In each generation, the targeted molecules are the major reaction product as detected by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The only separation needed is to remove the little unreacted monomer by simple precipitation or washing. This simple clicklike process without complicated purification is particularly suitable for the synthesis of custom-made polyester dendrimers.

  19. 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

    2015-07-14

    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.

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

    Science.gov (United States)

    Kaga, Sadik; Arslan, Mehmet; Sanyal, Rana; Sanyal, Amitav

    2016-04-15

    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.

  1. 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.

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

    Science.gov (United States)

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

    2014-12-01

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

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2005-03-15

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

  9. 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.

  10. 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.

  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. Assessment of nanopolyamidoamine-G7 dendrimer antibacterial effect in aqueous solution

    Directory of Open Access Journals (Sweden)

    Mitra Gholami

    2016-06-01

    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.

  14. 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.

  15. 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.

  16. Anionic linear-globular dendrimers: biocompatible hybrid materials with potential uses in nanomedicine.

    Science.gov (United States)

    Alavidjeh, Mohammad Shafiee; Haririan, Ismaeil; Khorramizadeh, Mohammad Reza; Ghane, Zohre Zarei; Ardestani, Mehdi Shafiee; Namazi, Hassan

    2010-04-01

    The use of dendrimers as nano-sized excipients/vectors in biological and pharmaceutical systems is dependent on the investigation of their toxicological profiles in biological media. In this study, a series of mechanistic in vitro structure-associated cell toxicity evaluations was performed on the two generations of an anionic linear-globular dendrimer G1 and G2 (where PEG is the core, and citric acid is the periphery) each of which has a different size, charge, and MW. In vitro cytotoxicity behavior of the dendrimers with the methods like crystal violet staining, methyl thiazolyl tetrazolium (MTT), and lactate dehydrogenase (LDH) assays was analyzed. The cell death mechanisms (apoptosis-necrosis) induced by the dendrimers were also evaluated in HT1080 cell line. The impact of the dendrimers on the release of the pro-inflammatory cytokines like TNF-alpha (tumor necrosis factor alpha) and IL1-beta (interleukin 1 beta) was assessed in THP-1 cell line. Hemolysis assay and coagulation studies such as PT (prothrombin time) and APTT (activated partial thromboplastin time) on human blood samples were conducted to examine the interactions of the dendrimers with such bio-environments. The results of cell cytotoxicity experiments and the amounts of IL1-beta and TNF-alpha secretions from THP-1 cell line were consistent with the hemoglobin release from the erythrocytes and the results gained from the coagulation studies. In fact, no significant harmful effect was observed for the dendrimers up to the concentration of 0.5 mg/ml. Both apoptosis and necrosis were ascribed to cell death. The G1 with more flexibility, less negative charge, and greater poly dispersity in size versus the G2 displayed more toxicity than the G2 at the concentration of 1 mg/ml and above in most of the experiments. As a whole, these results suggest a biocompatible range for these hybrid structures up to the concentration of 0.5 mg/ml. Therefore, the potentiality for these structures to be employed in the

  17. Oegylated and cross-linking carbazole dendrons and dendrimers: Synthesis, characterization, assembly and thin film fabrication

    Science.gov (United States)

    Felipe, Mary Jane Legaspi

    2011-12-01

    Dendrimers and dendrons (fractional dendrimers) are macromolecular structures that have well-defined molecular weights and precise number of functional groups. Tailoring these structures has provided designer molecules that can be used for various applications including drug delivery, sensors, and anti-biofouling surfaces. Overall, this dissertation provides novel protocols for the understanding of molecular design, synthesis, and structure-property relationship of OEGylated and conjugated carbazole dendrons and dendrimers. In this design, the use of oligo(ethylene glycol) (OEG) allows for the fabrication of biocompatible materials and imparts hydrophilicity on the structure while the carbazole functionality allows the cross-linking of these designer molecules. Such fine-tuning of macromolecular structures leading to the fabrication of anti-biofouling thin films, nanostructuring at the air-water interface, and assembly into supramolecular superstructures are considered in this dissertation. Chapter 2 details the synthesis, characterization, and electrochemical cross-linking of OEGylated linear dendrons and "Janus-type" dendrimers. Cross-linking the carbazole moieties enables the deposition of these films on Au, indium tin oxide-coated glass, and doped silicon through cyclic voltammetry and provides films with secondary level of organization imparted by the inter- and intra-molecular interaction among the carbazole units. Chapter 3 describes the fabrication of nonspecific protein adsorption resistant surfaces through electrochemical grafting of three different dendrons on SAM carbazole-coated gold substrates. The predictable shape of each dendron and the ability to cross-link the carbazole units have enabled parametrization of OEG conformation and density on these interfaces. Chapter 4 demonstrates the fundamental architectural requirements for obtaining stable films with OEGylated linear dendron molecules providing a new architectural design of nanostructuring

  18. 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

  19. 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...

  20. Atomic force microscopy probing of receptor-nanoparticle interactions for riboflavin receptor targeted gold-dendrimer nanocomposites.

    Science.gov (United States)

    Witte, Amanda B; Leistra, Abigail N; Wong, Pamela T; Bharathi, Sophia; Refior, Kevin; Smith, Phillip; Kaso, Ola; Sinniah, Kumar; Choi, Seok Ki

    2014-03-20

    Riboflavin receptors are overexpressed in malignant cells from certain human breast and prostate cancers, and they constitute a group of potential surface markers important for cancer targeted delivery of therapeutic agents and imaging molecules. Here we report on the fabrication and atomic force microscopy (AFM) characterization of a core-shell nanocomposite consisting of a gold nanoparticle (AuNP) coated with riboflavin receptor-targeting poly(amido amine) dendrimer. We designed this nanocomposite for potential applications such as a cancer targeted imaging material based on its surface plasmon resonance properties conferred by AuNP. We employed AFM as a technique for probing the binding interaction between the nanocomposite and riboflavin binding protein (RfBP) in solution. AFM enabled precise measurement of the AuNP height distribution before (13.5 nm) and after chemisorption of riboflavin-conjugated dendrimer (AuNP-dendrimer; 20.5 nm). Binding of RfBP to the AuNP-dendrimer caused a height increase to 26.7 nm, which decreased to 22.8 nm when coincubated with riboflavin as a competitive ligand, supporting interaction of AuNP-dendrimer and its target protein. In summary, physical determination of size distribution by AFM imaging can serve as a quantitative approach to monitor and characterize the nanoscale interaction between a dendrimer-covered AuNP and target protein molecules in vitro.

  1. Synthesis of Novel Amphiphilic Poly (ester-amine) Dendrimers and Their Recognition of Hg2+ at the Air/Water Interface

    Institute of Scientific and Technical Information of China (English)

    申亮; 李富友; 沙耀武; 潘峥峥; 洪啸吟; 黄春辉

    2003-01-01

    Two novel amphiphilic poly(ester-amine)dendrimers were synthesized and characterized by 1H NMR,13C NMR and IR spectra.Their properties of Langmuir film were investigated at the air/water interface.The relationship between the surface pressure and area isotherms of the dendrimers was found to be dependent on the nature of subphases,Interaction between HgCl2 and the dendrimers was observed,indicating that the amphiphilic dendrimers could act as a sensor for Hg2+.

  2. 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.

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

    Science.gov (United States)

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

    2014-03-13

    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 high quantum yield (QY) up to 58%. By preparing CdTe QDs within HPAMAM, the biocompatibility properties of HPAMAM and the optical, electrical properties of CdTe QDs can be combined, endowing the CdTe QDs with biocompatibility. The resulting CdTe QDs can be directly used in biomedical fields, and their potential application in bio-imaging was investigated.

  4. High-Resolution Imaging of Dendrimers Used in Drug Delivery via Scanning Probe Microscopy

    Directory of Open Access Journals (Sweden)

    Lifang Shi

    2011-01-01

    Full Text Available Dendrimers and telodendrimer micelles represent two new classes of vehicles for drug delivery that have attracted much attention recently. Their structural characterization at the molecular and submolecular level remains a challenge due to the difficulties in reaching high resolution when imaging small particles in their native media. This investigation offers a new approach towards this challenge, using scanning tunneling microscopy (STM and atomic force microscopy (AFM. By using new sample preparation protocols, this work demonstrates that (a intramolecular features such as drug molecules and dendrimer termini can be resolved; and (b telodendrimer micelles can be immobilized on the surface without compromising structural integrity, and as such, high resolution AFM imaging may be performed to attain 3D information. This high-resolution structural information should enhance our knowledge of the nanocarrier structure and nanocarrier-drug interaction and, therefore, facilitate design and optimization of the efficiency in drug delivery.

  5. 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.

  6. Triclosan-loaded poly(amido amine) dendrimer for simultaneous treatment and remineralization of human dentine.

    Science.gov (United States)

    Zhou, Yan; Yang, Jiaojiao; Lin, Zaifu; Li, Jiyao; Liang, Kunneng; Yuan, He; Li, Sheyu; Li, Jianshu

    2014-03-01

    In order to treat dental caries of damaged dentine, triclosan-loaded carboxyl-terminated poly(amido amine) dendrimer (PAMAM-COOH) is prepared and characterized. While being incubated in artificial saliva, triclosan-loaded PAMAM-COOH formulation can induce in situ remineralization of hydroxyapatite (HA) on etched dentine, and the regenerated HA has a similar crystal structure with natural dentine. It can also release the encapsulated triclosan for a long period. The interesting drug release profiles are controlled by both dendrimer encapsulation capability and the mineralization degree, which are ideal to obtain multifunctional properties of long-term release of anti-bacterial drug for local treatment during the remineralization process. The triclosan-loaded G4-COOH provides a general strategy to cure dental caries and repair damaged dentine at the same time, which forms a potential restorative material for dental repair.

  7. Palladium(0 Deposited on PAMAM Dendrimers as a Catalyst for C–C Cross Coupling Reactions

    Directory of Open Access Journals (Sweden)

    Tomasz Borkowski

    2011-01-01

    Full Text Available PAMAM dendrimers of generations G2–G3 as well as a partially substituted derivative of generation G4 and a low-molecular-weight tricyclic ligand 4 were used to bind Pd(0 nanoparticles. The obtained adducts were tested as catalysts for C–C cross-coupling reactions, such as the Suzuki-Miyaura, Hiyama, Heck and Sonogashira reaction. The highest yields of the coupling product, diphenylacetylene, were obtained with all the catalysts studied in the Sonogashira coupling performed in ethanol with K2CO3 as base. Very good results, 85–100%, were also found in the Suzuki-Miyaura cross-coupling, while the efficiency of the Hiyama coupling appeared lower, with 38–52% of 2-Methylbiphenyl formed. In all reactions, the G2–Pd(0 catalyst, containing an unmodified dendrimer, afforded the highest yields of the cross-coupling products.

  8. 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.

  9. 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.

  10. 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.

  11. Deposition of Silver Nanoparticles on Dendrimer Functionalized Multiwalled Carbon Nanotubes: Synthesis, Characterization and Antimicrobial Activity

    OpenAIRE

    2011-01-01

    The nanohybrids composed of silver nanoparticles and aromatic polyamide functionalized multiwalled carbon nanotubes (MWCNTs) is successfully synthesized and tested for their antibacterial activity against different pathogens. Prior to deposition of silver nanoparticles, acid treated MWCNTs (MWCNTs-COOH) were successively reacted with p-phenylenediamine and methylmethacrylate to form series of NH2-terminated aromatic polyamide dendrimers on the surface of MWCNTs through Michael addition and am...

  12. 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

    generation were synthesized and investigated as potential materials for high capacity optical data storage with their dimerization efficiency compared to uracil as a reference compound. This allows the impact of increasing the generation number of the dendrimers, both the number of chromophores, as well...... nm with an intensity of 70 mW/cm(2) could be obtained suggesting future use as recording media for optical data storage. (c) 2007 Wiley Periodicals, Inc....

  13. 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.

  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. Synthetic cation-selective nanotube: Permeant cations chaperoned by anions

    Science.gov (United States)

    Hilder, Tamsyn A.; Gordon, Dan; Chung, Shin-Ho

    2011-01-01

    The ability to design ion-selective, synthetic nanotubes which mimic biological ion channels may have significant implications for the future treatment of bacteria, diseases, and as ultrasensitive biosensors. We present the design of a synthetic nanotube made from carbon atoms that selectively allows monovalent cations to move across and rejects all anions. The cation-selective nanotube mimics some of the salient properties of biological ion channels. Before practical nanodevices are successfully fabricated it is vital that proof-of-concept computational studies are performed. With this in mind we use molecular and stochastic dynamics simulations to characterize the dynamics of ion permeation across a single-walled (10, 10), 36 Å long, carbon nanotube terminated with carboxylic acid with an effective radius of 5.08 Å. Although cations encounter a high energy barrier of 7 kT, its height is drastically reduced by a chloride ion in the nanotube. The presence of a chloride ion near the pore entrance thus enables a cation to enter the pore and, once in the pore, it is chaperoned by the resident counterion across the narrow pore. The moment the chaperoned cation transits the pore, the counterion moves back to the entrance to ferry another ion. The synthetic nanotube has a high sodium conductance of 124 pS and shows linear current-voltage and current-concentration profiles. The cation-anion selectivity ratio ranges from 8 to 25, depending on the ionic concentrations in the reservoirs.

  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.

  17. 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.

  18. 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.

  19. Low temperature synthesis of ordered mesoporous stable anatase nanocrystals: the phosphorus dendrimer approach.

    Science.gov (United States)

    Brahmi, Younes; Katir, Nadia; Ianchuk, Mykhailo; Collière, Vincent; Essassi, El Mokhtar; Ouali, Armelle; Caminade, Anne-Marie; Bousmina, Mosto; Majoral, Jean Pierre; El Kadib, Abdelkrim

    2013-04-07

    The scarcity of low temperature syntheses of anatase nanocrystals prompted us to explore the use of surface-reactive fourth generation phosphorus-dendrimers as molds to control the nucleation and growth of titanium-oxo-species during the sol-gel mineralization process. Unexpectedly, the dendritic medium provides at low temperature, discrete anatase nanocrystals (4.8 to 5.2 nm in size), in marked contrast to the routinely obtained amorphous titanium dioxide phase under standard conditions. Upon thermal treatment, heteroatom migration from the branches to the nanoparticle surface and the ring opening polymerization of the cyclophosphazene core provide stable, interpenetrating mesoporous polyphosphazene-anatase hybrid materials (-P[double bond, length as m-dash]N-)n-TiO2. The steric hindrance of the dendritic skeleton, the passivation of the anatase surface by heteroatoms and the ring opening of the core limit the crystal growth of anatase to 7.4 nm and prevent, up to 800 °C, the commonly observed anatase-to-rutile phase transformation. Performing this mineralization in the presence of similar surface-reactive but non-dendritic skeletons (referred to as branch-mimicking dendrimers) failed to generate crystalline anatase and to efficiently limit the crystal growth, bringing thus clear evidence of the virtues of phosphorus dendrimers in the design of novel nanostructured materials.

  20. Asymmetric cation-binding catalysis

    DEFF Research Database (Denmark)

    Oliveira, Maria Teresa; Lee, Jiwoong

    2017-01-01

    and KCN, are selectively bound to the catalyst, providing exceptionally high enantioselectivities for kinetic resolutions, elimination reactions (fluoride base), and Strecker synthesis (cyanide nucleophile). Asymmetric cation-binding catalysis was recently expanded to silicon-based reagents, enabling...... solvents, thus increasing their applicability in synthesis. The expansion of this concept to chiral polyethers led to the emergence of asymmetric cation-binding catalysis, where chiral counter anions are generated from metal salts, particularly using BINOL-based polyethers. Alkali metal salts, namely KF...

  1. Tailor-made graphite oxide-DAB poly(propylene imine) dendrimer intercalated hybrids and their potential for efficient CO2 adsorption

    NARCIS (Netherlands)

    Tsoufis, T.; Katsaros, F.; Sideratou, Z.; Romanos, G.; Ivashenko, O.; Rudolf, P.; Kooi, B. J.; Papageorgiou, S.; Karakassides, M. A.

    2014-01-01

    We report the rational design and synthesis of DAB poly(propylene imine) dendrimer (DAB) intercalated graphite oxide (GO) hybrids with tailorable interlayer distances. The amine groups originating from the intercalated dendrimer molecules cross-link adjacent GO sheets and strongly favour CO2 adsorpt

  2. 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.

  3. 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.

  4. 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.

  5. Continuous flow atomic force microscopy imaging reveals fluidity and time-dependent interactions of antimicrobial dendrimer with model lipid membranes.

    Science.gov (United States)

    Lind, Tania Kjellerup; Zielińska, Paulina; Wacklin, Hanna Pauliina; Urbańczyk-Lipkowska, Zofia; Cárdenas, Marité

    2014-01-28

    In this paper, an amphiphilic peptide dendrimer with potential applications against multi-resistant bacteria such as Staphylococcus aureus was synthesized and studied on model cell membranes. The combination of quartz crystal microbalance and atomic force microscopy imaging during continuous flow allowed for in situ monitoring of the very initial interaction processes and membrane transformations on longer time scales. We used three different membrane compositions of low and high melting temperature phospholipids to vary the membrane properties from a single fluid phase to a pure gel phase, while crossing the phase coexistence boundaries at room temperature. The interaction mechanism of the dendrimer was found to be time-dependent and to vary remarkably with the fluidity and coexistence of liquid-solid phases in the membrane. Spherical micelle-like dendrimer-lipid aggregates were formed in the fluid-phase bilayer and led to partial solubilization of the membrane, while in gel-phase membranes, the dendrimers caused areas of local depressions followed by redeposition of flexible lipid patches. Domain coexistence led to a sequence of events initiated by the formation of a ribbon-like network and followed by membrane solubilization via spherical aggregates from the edges of bilayer patches. Our results show that the dendrimer molecules were able to destroy the membrane integrity through different mechanisms depending on the lipid phase and morphology and shed light on their antimicrobial activity. These findings could have an impact on the efficacy of the dendrimers since lipid membranes in certain bacteria have transition temperatures very close to the host body temperature.

  6. Pulmonary administration of a doxorubicin-conjugated dendrimer enhances drug exposure to lung metastases and improves cancer therapy.

    Science.gov (United States)

    Kaminskas, Lisa M; McLeod, Victoria M; Ryan, Gemma M; Kelly, Brian D; Haynes, John M; Williamson, Mark; Thienthong, Neeranat; Owen, David J; Porter, Christopher J H

    2014-06-10

    Direct administration of chemotherapeutic drugs to the lungs significantly enhances drug exposure to lung resident cancers and may improve chemotherapy when compared to intravenous administration. Direct inhalation of uncomplexed or unencapsulated cytotoxic drugs, however, leads to bolus release and unacceptable lung toxicity. Here, we explored the utility of a 56kDa PEGylated polylysine dendrimer, conjugated to doxorubicin, to promote the controlled and prolonged exposure of lung-resident cancers to cytotoxic drug. After intratracheal instillation to rats, approximately 60% of the dendrimer was rapidly removed from the lungs (within 24h) via mucociliary clearance and absorption into the blood. This was followed by a slower clearance phase that reflected both absorption from the lungs (bioavailability 10-13%) and biodegradation of the dendrimer scaffold. After 7days, approximately 15% of the dose remained in the lungs. A syngeneic rat model of lung metastasised breast cancer was subsequently employed to compare the anticancer activity of the dendrimer with a doxorubicin solution formulation after intravenous and pulmonary administration. Twice weekly intratracheal instillation of the dendrimer led to a >95% reduction in lung tumour burden after 2weeks in comparison to IV administration of doxorubicin solution which reduced lung tumour burden by only 30-50%. Intratracheal instillation of an equivalent dose of doxorubicin solution led to extensive lung-related toxicity and death withinseveral days of a single dose. The data suggest that PEGylated dendrimers have potential as inhalable drug delivery systems to promote the prolonged exposure of lung-resident cancers to chemotherapeutic drugs and to improve anti-cancer activity.

  7. 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

  8. Energetics of dendrimer binding to HIV-1 gp120-CD4 complex and mechanismic aspects of its role as an entry-inhibitor

    Science.gov (United States)

    Saurabh, Suman; Sahoo, Anil Kumar; Maiti, Prabal K.

    2016-10-01

    Experiments and computational studies have established that de-protonated dendrimers (SPL7013 and PAMAM) act as entry-inhibitors of HIV. SPL7013 based Vivagel is currently under clinical development. The dendrimer binds to gp120 in the gp120-CD4 complex, destabilizes it by breaking key contacts between gp120 and CD4 and prevents viral entry into target cells. In this work, we provide molecular details and energetics of the formation of the SPL7013-gp120-CD4 ternary complex and decipher modes of action of the dendrimer in preventing viral entry. It is also known from experiments that the dendrimer binds weakly to gp120 that is not bound to CD4. It binds even more weakly to the CD4-binding region of gp120 and thus cannot directly block gp120-CD4 complexation. In this work, we examine the feasibility of dendrimer binding to the gp120-binding region of CD4 and directly blocking gp120-CD4 complex formation. We find that the process of the dendrimer binding to CD4 can compete with gp120-CD4 binding due to comparable free energy change for the two processes, thus creating a possibility for the dendrimer to directly block gp120-CD4 complexation by binding to the gp120-binding region of CD4.

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

    Directory of Open Access Journals (Sweden)

    Ceña-Diez R

    2016-05-01

    Full Text Available Rafael Ceña-Diez,1–4,* Pilar García-Broncano,1–5,* Francisco Javier de la Mata,4,6 Rafael Gómez,4,6 Mª Ángeles Muñoz-Fernández1–4 1Hospital General Universitario Gregorio Marañon, 2Instituto de Investigación Sanitaria Gregorio Marañon, 3Spanish HIV HGM Biobank, 4Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN, 5Laboratory of Viral Infection and Immunity, National Center of Microbiology, Health Institute of Carlos III, Majadahonda, 6Department of Organic Chemistry and Inorganic Chemistry, University of Alcalá, Alcalá de Henares, Madrid, Spain *These authors contributed equally to this work Abstract: 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. Keywords: G2-S16, dendrimer, HIV-1, SEVI, microbicide, antiretrovirals

  10. Development of TRPN dendrimer-modified disordered mesoporous silica for CO{sub 2} capture

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xiaoyun; Zhang, Sisi; Qin, Hongyan; Wu, Wei, E-mail: wuweiupc@upc.edu.cn

    2014-08-15

    Highlights: • A novel series of TRPN dendrimers are synthesized. • Structurally disordered mesoporous silica was used to develop the CO{sub 2} adsorbent. • The CO{sub 2} adsorption capacity is relatively high. • The sorbent exhibits a high stability after 12 cycling runs. • The sorbent achieves complete desorption at low temperature (60 °C). - Abstract: A novel series of tri(3-aminopropyl) amine (TRPN) dendrimers were synthesized and impregnated on structurally disordered mesoporous silica (DMS) to generate CO{sub 2} adsorbents (TS). The physicochemical and adsorption properties of the adsorbents before and after dendrimer modification were characterized by X-ray diffraction (XRD), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and N{sub 2} adsorption–desorption (N{sub 2}-BET) techniques. CO{sub 2} adsorption–desorption tests indicated that the sorbent demonstrates high CO{sub 2} adsorption capacity (138.1 mg g{sup −1} for G1 sample TS-G1-3CN-50 and 91.7 mg g{sup −1} for G2 sample TS-G2-6CN-50), and can completely desorb CO{sub 2} under vacuum at 60 °C. Its CO{sub 2} adsorption capacity at 25 °C increases with the amine loading, achieving the highest adsorption capacity (140.6 mg g{sup −1} for TS-G1-3CN) at 60%. The developed TS materials exhibited excellent cycling stability. After 12 consecutive adsorption–desorption runs, TS-G1-3CN-50 shows an adsorption capacity of 136.0 mg g{sup −1}, retaining 98.5% of its original value.

  11. Lyophilized mucoadhesive-dendrimer enclosed matrix tablet for extended oral delivery of albendazole.

    Science.gov (United States)

    Mansuri, Shakir; Kesharwani, Prashant; Tekade, Rakesh Kumar; Jain, Narendra Kumar

    2016-05-01

    Dendrimers are multifunctional carriers widely employed for delivering drugs in a variety of disease conditions including HIV/AIDS and cancer. Albendazole (ABZ) is a commonly used anthelmintic drug in human as well as veterinary medicine. In this investigation, ABZ was formulated as a "muco-dendrimer" based sustained released tablet. The mucoadhesive complex was synthesized by anchoring chitosan to fifth generation PPI dendrimer (Muco-PPI) and characterized by UV, FTIR, (1)H NMR spectroscopy and electron microscopy. ABZ was entrapped inside Muco-PPI followed by lyophilization and tableting as matrix tablet. A half-life (t1/2) of 8.06±0.15, 8.17±0.47, 11.04±0.73, 11.49±0.92, 12.52±1.04 and 16.9±1.18h was noted for ABZ (free drug), conventional ABZ tablet (F1), conventional ABZ matrix tablet (F2), PPI-ABZ complex, PPI-ABZ matrix tablet (F3) and Muco-PPI-ABZ matrix tablet (F4), respectively. Thus the novel mucoadhesive-PPI based formulation of ABZ (F4) increased the t1/2 of ABZ significantly by almost twofold as compared to the administration of free drug. The in vivo drug release data showed that the Muco-PPI based formulations have a significantly higher Cmax (2.40±0.02μg/mL) compared with orally administered free ABZ (0.19±0.07μg/mL) as well as conventional tablet (0.20±0.05μg/mL). In addition, the Muco-PPI-ABZ matrix tablet displayed increased mean residence time (MRT) and is therefore a potential candidate to appreciably improve the pharmacokinetic profile of ABZ.

  12. Efficient light harvesting and energy transfer in a red phosphorescent iridium dendrimer.

    Science.gov (United States)

    Cho, Yang-Jin; Hong, Seong Ahn; Son, Ho-Jin; Han, Won-Sik; Cho, Dae Won; Kang, Sang Ook

    2014-12-15

    A series of red phosphorescent iridium dendrimers of the type [Ir(btp)2(pic-PCn)] (Ir-Gn; n = 0, 1, 2, and 3) with two 2-(benzo[b]thiophen-2-yl)pyridines (btp) and 3-hydroxypicolinate (pic) as the cyclometalating and ancillary ligands were prepared in good yields. Dendritic generation was grown at the 3 position of the pic ligand with 4-(9H-carbazolyl)phenyl dendrons connected to 3,5-bis(methyleneoxy)benzyloxy branches (PCn; n = 0, 2, 4, and 8). The harvesting photons on the PCn dendrons followed by efficient energy transfer to the iridium center resulted in high red emissions at ∼600 nm by metal-to-ligand charge transfer. The intensity of the phosphorescence gradually increased with increasing dendrimer generation. Steady-state and time-resolved spectroscopy were used to investigate the energy-transfer mechanism. On the basis of the fluorescence quenching rate constants of the PCn dendrons, the energy-transfer efficiencies for Ir-G1, Ir-G2, and Ir-G3 were 99, 98, and 96%, respectively. The energy-transfer efficiency for higher-generation dendrimers decreased slightly because of the longer distance between the PC dendrons and the core iridium(III) complex, indicating that energy transfer in Ir-Gn is a Förster-type energy transfer. Finally, the light-harvesting efficiencies for Ir-G1, Ir-G2, and Ir-G3 were determined to be 162, 223, and 334%, respectively.

  13. Zero-field-cooled/field-cooled magnetization study of Dendrimer model

    Science.gov (United States)

    Arejdal, M.; Bahmad, L.; Benyoussef, A.

    2017-01-01

    Being motivated by Dendrimer model with mixed spins σ=3 and S=7/2, we investigated the magnetic nanoparticle system in this study. We analyzed and discussed the ground-state phase diagrams and the stable phases. Then, we elaborated and explained the magnetic properties of the system by using Monte Carlo Simulations (MCS) in the framework of the Ising model. In this way, we determined the blocking temperature, which is deduced through studying the partial-total magnetization and susceptibility as a function of the temperature, and we established the effects of both the exchange coupling interaction and the crystal field on the hysteresis loop.

  14. POxylated Polyurea Dendrimers: Smart Core-Shell Vectors with IC50 Lowering Capacity.

    Science.gov (United States)

    Restani, Rita B; Conde, João; Pires, Rita F; Martins, Pedro; Fernandes, Alexandra R; Baptista, Pedro V; Bonifácio, Vasco D B; Aguiar-Ricardo, Ana

    2015-08-01

    The design and preparation of highly efficient drug delivery platforms using green methodologies is at the forefront of nanotherapeutics research. POxylated polyurea dendrimers are efficiently synthesized using a supercritical-assisted polymerization in carbon dioxide. These fluorescent, pH-responsive and water-soluble core-shell smart nanocarriers show low toxicity in terms of cell viability and absence of glutathione depletion, two of the major side effect limitations of current vectors. The materials are also found to act as good transfection agents, through a mechanism involving an endosomal pathway, being able to reduce 100-fold the IC50 of paclitaxel.

  15. A General Procedure for Surface Modification of Nano-alumina and Its Application to Dendrimers

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A general procedure for surface modification of nano-alumina using N, N'-dicyclohexyl-carbodiimide (DCC) mediated amidation is reported. Aliphatic and aromatic carboxylic acids reacted smoothly with nano-alumina pretreated with 3-aminopropyltriethoxysilane in the presence of DCC, giving modified aluminas having organic surfaces. The grafted aluminas have been characterized qualitatively by FT-IR or 13C CPMAS NMR spectroscopy, and quantitatively by thermogravimetric analysis and elemental analysis. The procedure was applied to polyether dendrons bearing carboxyl groups at the focal points, giving successful grafting of dendrimers onto nano-alumina.

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. Room-Temperature Single-Electron Tunneling in Dendrimer-Stabilized Gold Nanoparticles Anchored at a Molecular Printboard

    NARCIS (Netherlands)

    Nijhuis, Christian A.; Oncel, Nuri; Huskens, Jurriaan; Zandvliet, Harold J.W.; Ravoo, Bart Jan; Poelsema, Bene; Reinhoudt, David N.

    2006-01-01

    Particle in a box: A gold nanoparticle is encapsulated in a fifth-generation guest dendrimer, which binds to a host self-assembled monolayer surface (see figure). The nanoparticle encapsulated in the “molecular box” is a supramolecular junction that exhibits single-electron tunneling at room tempera

  2. 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

  3. Dendrimer-encapsulated Pd nanoparticles as catalysts for C-C cross-couplings in flow microreactors

    NARCIS (Netherlands)

    Ricciardi, R.; Huskens, J.; Verboom, W.

    2015-01-01

    The inner walls of glass microreactors were functionalized with dendrimer-encapsulated Pd nanoparticles. The catalysts were efficient for the Heck–Cassar (copper-free Sonogashira) and Suzuki–Miyaura (SMC) cross-coupling reactions. For the Heck–Cassar reaction between iodobenzene and phenylacetylene,

  4. Synthesis of Novel Hydrocarbon Soluble Multifunctional Anionic Initiators: Tools for Synthesis of Novel Dendrimer and Molecular Brush Polymer Architectures

    Science.gov (United States)

    2015-02-09

    SECURITY CLASSIFICATION OF: A novel hydrocarbon -soluble trifunctional organolithium initiator, with no polar-additive requirements, has been synthesized...Approved for Public Release; Distribution Unlimited Final Report: Synthesis of Novel Hydrocarbon Soluble Multifunctional Anionic Initiators: Tools for...journals: Final Report: Synthesis of Novel Hydrocarbon Soluble Multifunctional Anionic Initiators: Tools for Synthesis of Novel Dendrimer and Molecular

  5. Stepwise Synthesis of Mesoporous Carbon Nitride Functionalized by Melamine Based Dendrimer Amines for Adsorption of CO2 and CH4

    Directory of Open Access Journals (Sweden)

    Mansoor Anbia

    2016-12-01

    Full Text Available In this study, a novel solid dendrimer amine (hyperbranched polymers was prepared using mesoporous carbon nitride functionalized by melamine based dendrimer amines. This adsorbent was denoted MDA-MCN-1. The process was stepwise synthesis and hard-templating method using mesoporous silica SBA-15 as a template. Cyanuric chloride and N,N-diisopropylethylamine (DIPEA, Merck were used for functionalization of the MCN-1. Fourier transform infrared spectroscopy (FT-IR, Nitrogen adsorption-desorption analysis, Small Angle X-ray Scattering (SAXS, X-ray diffraction (XRD and thermogravimetric analysis (TGA were used for characterization of the adsorbent. This material was used for carbon dioxide gas (CO2 and methane gas (CH4 adsorption at high pressure (up to 20 bar and room temperature. The volumetric method was used for the tests of the gas adsorption. The CO2 adsorption capacity of modified mesoporous carbon nitrides was about 4 mmol CO2 per g adsorbent. The methane adsorption capacity of this material was less than that CO2. Modified Mesoporous Carbon Nitride adsorbed about 3.52 mmol CH4 /g adsorbent. The increment of melamine based dendrimer generation on mesoporous surface increased adsorption capacity of both carbon dioxide and methane gases. According to the results obtained, the solid dendrimer amines, (MDA-MCN-1, performs excellently for CO2 and CH4 capture from flow gases and CO2 and CH4 storage.

  6. Influence of the Au/Ag ratio on the catalytic activity of dendrimer-encapsulated bimetallic nanoparticles in microreactors

    NARCIS (Netherlands)

    Ricciardi, R.; Huskens, J.; Verboom, W.

    2015-01-01

    Dendrimer-encapsulated Au/Ag alloy nanoparticles (Au/Ag DENs) were covalently attached to a monolayer-functionalized inner surface of glass microreactors. The influence of the bimetallic alloy structure and of the different metal ratios was investigated for the reduction of 4-nitrophenol using NaBH4

  7. 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

  8. Heavy metal cations permeate the TRPV6 epithelial cation channel.

    Science.gov (United States)

    Kovacs, Gergely; Danko, Tamas; Bergeron, Marc J; Balazs, Bernadett; Suzuki, Yoshiro; Zsembery, Akos; Hediger, Matthias A

    2011-01-01

    TRPV6 belongs to the vanilloid family of the transient receptor potential channel (TRP) superfamily. This calcium-selective channel is highly expressed in the duodenum and the placenta, being responsible for calcium absorption in the body and fetus. Previous observations have suggested that TRPV6 is not only permeable to calcium but also to other divalent cations in epithelial tissues. In this study, we tested whether TRPV6 is indeed also permeable to cations such as zinc and cadmium. We found that the basal intracellular calcium concentration was higher in HEK293 cells transfected with hTRPV6 than in non-transfected cells, and that this difference almost disappeared in nominally calcium-free solution. Live cell imaging experiments with Fura-2 and NewPort Green DCF showed that overexpression of human TRPV6 increased the permeability for Ca(2+), Ba(2+), Sr(2+), Mn(2+), Zn(2+), Cd(2+), and interestingly also for La(3+) and Gd(3+). These results were confirmed using the patch clamp technique. (45)Ca uptake experiments showed that cadmium, lanthanum and gadolinium were also highly efficient inhibitors of TRPV6-mediated calcium influx at higher micromolar concentrations. Our results suggest that TRPV6 is not only involved in calcium transport but also in the transport of other divalent cations, including heavy metal ions, which may have toxicological implications.

  9. The adjuvant mechanism of cationic dimethyldioctadecylammonium liposomes

    DEFF Research Database (Denmark)

    Korsholm, Karen Smith; Agger, Else Marie; Foged, Camilla;

    2007-01-01

    Cationic liposomes are being used increasingly as efficient adjuvants for subunit vaccines but their precise mechanism of action is still unknown. Here, we investigated the adjuvant mechanism of cationic liposomes based on the synthetic amphiphile dimethyldioctadecylammonium (DDA). The liposomes ...

  10. 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

  11. Synthesis of ethylene diamine-based ferrocene terminated dendrimers and their application as burning rate catalysts.

    Science.gov (United States)

    Zain-Ul-Abdin; Wang, Li; Yu, Haojie; Saleem, Muhammad; Akram, Muhammad; Khalid, Hamad; Abbasi, Nasir M; Yang, Xianpeng

    2017-02-01

    Ferrocene-based derivatives are widely used as ferrocene-based burning rate catalysts (BRCs) for ammonium perchlorate (AP)-based propellant. However, in long storage, small ferrocene-based derivatives migrate to the surface of the propellant, which results in changes in the designed burning parameters and finally causes unstable combustion. To retard the migration of ferrocene-based BRCs in the propellant and to increase the combustion of the solid propellant, zero to third generation ethylene diamine-based ferrocene terminated dendrimers (0G, 1G, 2G and 3G) were synthesized. The synthesis of these dendrimers was confirmed by (1)H NMR and FT-IR spectroscopy. The electrochemical behavior of 0G, 1G, 2G and 3G was investigated by cyclic voltammetry (CV) and the burning rate catalytic activity of 0G, 1G, 2G and 3G on thermal disintegration of AP was examined by thermogravimetry (TG) and differential thermogravimetry (DTG) techniques. Anti-migration studies show that 1G, 2G and 3G exhibit improved anti-migration behavior in the AP-based propellant.

  12. 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.

  13. 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

  14. The use of PAMAM dendrimers as a platform for laccase immobilization: kinetic characterization of the enzyme.

    Science.gov (United States)

    Cardoso, Franciane Pinheiro; Aquino Neto, Sidney; Ciancaglini, Pietro; de Andrade, Adalgisa R

    2012-08-01

    The kinetic behavior of the enzyme laccase in solution and immobilized onto carbon platforms using poly(amido amine) (PAMAM) dendrimers has been investigated. The results with the immobilized enzymes have demonstrated that almost ten times more enzyme on the carbon support is required for satisfactory kinetic rates to be achieved. Furthermore, the study as a function of the substrate concentration revealed that the kinetic behavior of the enzyme in solution fits the Michaelis-Menten model. However, when the enzyme is immobilized onto the carbon surface, the catalyzed reaction follows a particular kinetic behavior with apparent positive cooperativity. The highest activity with laccase (in solution or immobilized) is achieved around pH 4.5, and the substrate conversion rate clearly diminishes with rising pH. The optimum temperature lies around 60 °C. The enzyme displays good catalytic activity in a wide range of pH and temperature values. The stability tests evidenced that there is no appreciable reduction in the enzymatic activity after immobilization within the first 30 days. Taking into account both the kinetic and stability tests, one can infer that the use of PAMAM dendrimers seems to be a very attractive approach for the immobilization of enzymes, as well as a feasible and useful methodology for the anchoring of enzymes with potential application in many biotechnological areas.

  15. 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.

  16. Molecular Modeling of PEGylated Peptides, Dendrimers, and Single-Walled Carbon Nanotubes for Biomedical Applications

    Directory of Open Access Journals (Sweden)

    Hwankyu Lee

    2014-03-01

    Full Text Available Polyethylene glycol (PEG has been conjugated to many drugs or drug carriers to increase their solubility and circulating lifetime, and reduce toxicity. This has motivated many experimental studies to understand the effect of PEGylation on delivery efficiency. To complement the experimental findings and uncover the mechanism that cannot be captured by experiments, all-atom and coarse-grained molecular dynamics (MD simulations have been performed. This has become possible, due to recent advances in simulation methodologies and computational power. Simulations of PEGylated peptides show that PEG chains wrap antimicrobial peptides and weaken their binding interactions with lipid bilayers. PEGylation also influences the helical stability and tertiary structure of coiled-coil peptides. PEGylated dendrimers and single-walled carbon nanotubes (SWNTs were simulated, showing that the PEG size and grafting density significantly modulate the conformation and structure of the PEGylated complex, the interparticle aggregation, and the interaction with lipid bilayers. In particular, simulations predicted the structural transition between the dense core and dense shell of PEGylated dendrimers, the phase behavior of self-assembled complexes of lipids, PEGylated lipids, and SWNTs, which all favorably compared with experiments. Overall, these new findings indicate that simulations can now predict the experimentally observed structure and dynamics, as well as provide atomic-scale insights into the interactions of PEGylated complexes with other molecules.

  17. Synthesis of nanoparticle-cored dendrimers by convergent dendritic functionalization of monolayer-protected nanoparticles.

    Science.gov (United States)

    Shon, Young-Seok; Choi, Daeock; Dare, Jonathan; Dinh, Tuong

    2008-06-01

    This article presents a synthesis method for nanoparticle-cored dendrimers (NCDs), which have dendritic architectures around a monolayer-protected gold nanoparticle. The synthesis method is based on a strategy in which the synthesis of monolayer-protected nanoparticles is followed by adding dendrons on functionalized nanoparticles by a single coupling reaction. NMR spectroscopy, IR spectroscopy, and thermogravimetric analysis (TGA) characterizations confirmed the successful coupling reaction between dendrons with different generations ([G1], [G2], and [G3]) and COOH-functionalized nanoparticles ( approximately Au201L71). The dendrimer wedge density also could be controlled by reacting nanoparticles having different loading of COOH groups ( approximately 60 and approximately 10% COOH of the 71 ligands per gold nanoparticle) with functionalized dendrons. Transmission electron microscope results showed that this synthesis strategy maintains the average size of the nanoparticle core during dendron coupling reactions. This control over the composition and core size makes the systematic study of NCDs with different generations possible. The chemical stability of NCDs was found to be affected by dendron generation around the nanoparticle core. The current-potential response of NCD films on microelectrode arrays exhibited better electrical conductivity for NCDs with lower dendron generation.

  18. Promising Low-Toxicity of Viologen-Phosphorus Dendrimers against Embryonic Mouse Hippocampal Cells

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Majoral

    2013-09-01

    Full Text Available A new class of viologen-phosphorus dendrimers (VPDs has been recently shown to possess the ability to inhibit neurodegenerative processes in vitro. Nevertheless, in the Central Nervous Systems domain, there is little information on their impact on cell functions, especially on neuronal cells. In this work, we examined the influence of two VPD (VPD1 and VPD3 of zero generation (G0 on murine hippocampal cell line (named mHippoE-18. Extended analyses of cell responses to these nanomolecules comprised cytotoxicity test, reactive oxygen species (ROS generation studies, mitochondrial membrane potential (ΔΨm assay, cell death detection, cell morphology assessment, cell cycle studies, as well as measurements of catalase (CAT activity and glutathione (GSH level. The results indicate that VPD1 is more toxic than VPD3. However, these two tested dendrimers did not cause a strong cellular response, and induced a low level of apoptosis. Interestingly, VPD1 and VPD3 treatment led to a small decline in ROS level compared to untreated cells, which correlated with slightly increased catalase activity. This result indicates that the VPDs can indirectly lower the level of ROS in cells. Summarising, low-cytotoxicity on mHippoE-18 cells together with their ability to quench ROS, make the VPDs very promising nanodevices for future applications in the biomedical field as nanocarriers and/or drugs per se.

  19. 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.

  20. 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.

  1. Platinum and Other Transition Metal Nanoclusters (Pd, Rh) Stabilized by PAMAM Dendrimer as Excellent Heterogeneous Catalysts: Application to the Methylcyclopentane (MCP) Hydrogenative Isomerization.

    Science.gov (United States)

    Deraedt, Christophe; Melaet, Gérôme; Ralston, Walter T; Ye, Rong; Somorjai, Gabor A

    2017-03-08

    Pt, Rh, and Pd nanoclusters stabilized by PAMAM dendrimer are used for the first time in a gas flow reactor at high temperature (150-250 °C). Pt nanoclusters show a very high activity for the hydrogenation of the methylcyclopentane (MCP) at 200-225 °C with turnover freqency (TOF) up to 334 h(-1) and selectivity up to 99.6% for the ring opening isomerization at very high conversion (94%). Rh nanoclusters show different selectivity for the reaction, that is, ring opening isomerization at 175 °C and cracking at higher temperature whereas Pd nanoclusters perform ring enlargement plus dehydrogenation, while maintaining a high activity. The difference in these results as compared to unsupported/uncapped nanoparticles, demonstrates the crucial role of dendrimer. The tunability of the selectivity of the reaction as well as the very high activity of the metal nanoclusters stabilized by dendrimer under heterogeneous conditions open a new application for dendrimer catalysts.

  2. 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.

  3. Smart AS1411-aptamer conjugated pegylated PAMAM dendrimer for the superior delivery of camptothecin to colon adenocarcinoma in vitro and in vivo.

    Science.gov (United States)

    Alibolandi, Mona; Taghdisi, Seyed Mohammad; Ramezani, Pouria; Hosseini Shamili, Fazileh; Farzad, Sara Amel; Abnous, Khalil; Ramezani, Mohammad

    2017-03-15

    In the current study camptothecin-loaded pegylated PAMAM dendrimer were synthesized and were functionalized with AS1411 anti-nucleolin aptamers for site-specific targeting against colorectal cancer cells which over expresses nucleolin receptors. The morphological properties and size dispersity of the prepared nanoparticles were evaluated using transmission electron microscope (TEM) and DLS. The drug-loading content and encapsulation efficiency were obtained 8.1% and 93.67% respectively. The in vitro release of camptothecin from the formulation was provided the sustained release of encapsulated camptothecin during 4days. Comparative in vitro cytotoxicity experiments demonstrated that the targeted camptothecin loaded-pegylated dendrimers had higher antiproliferation activity, towards nucleolin-positive HT29 and C26 colorectal cancer cells than nucleolin-negative CHO cell line. Fluorscence microscopy and flow cytometry also confirmed the enhanced cellular uptake of AS1411 targeted pegylated-dendrimer. In vivo study in C26 tumor-bearing BALB/C mice revealed that the AS1411-functionalized camptothecin loaded pegylated dendrimers improved antitumor activity and survival rate of the encapsulated camptothecin. Conjugation of AS1411 aptamer to the camptothecin loaded-pegylated dendrimer surface provides site-specific delivery of camptothecin, inhibit C26 tumor growth in vivo and significantly decrease systemic toxicity. These results suggested that the new nucleolin-targeted pegylated PAMAM dendrimer as a delivery system for camptothecin have the potential for the treatment of nucleolin-overexpressed colorectal cancer.

  4. 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.

  5. Tailored control and optimisation of the number of phosphonic acid termini on phosphorus-containing dendrimers for the ex-vivo activation of human monocytes.

    Science.gov (United States)

    Rolland, Olivier; Griffe, Laurent; Poupot, Mary; Maraval, Alexandrine; Ouali, Armelle; Coppel, Yannick; Fournié, Jean-Jacques; Bacquet, Gérard; Turrin, Cédric-Olivier; Caminade, Anne-Marie; Majoral, Jean-Pierre; Poupot, Rémy

    2008-01-01

    The syntheses of a series of phosphonic acid-capped dendrimers is described. This collection is based on a unique set of dendritic structural parameters-cyclo(triphosphazene) core, benzylhydrazone branches and phosphonic acid surface-and was designed to study the influence of phosphonate (phosphonic acid) surface loading towards the activation of human monocytes ex vivo. Starting from the versatile hexachloro-cyclo(triphosphazene) N(3)P(3)Cl(6), six first-generation dendrimers were obtained, bearing one to six full branches, that lead to 4, 8, 12, 16, 20 and 24 phosphonate termini, respectively. The surface loading was also explored at the limit of dense packing by means of a first-generation dendrimer having a cyclo(tetraphosphazene) core and bearing 32 termini, and with a first-generation dendrimer based on a AB(2)/CD(5) growing pattern and bearing 60 termini. Human monocyte activation by these dendrimers confirms the requirement of the whole dendritic structure for bioactivity and identifies the dendrimer bearing four branches, thus 16 phosphonate termini, as the most bioactive.

  6. 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

  7. 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.

  8. 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.

  9. Site-selective Cu deposition on Pt dendrimer-encapsulated nanoparticles: correlation of theory and experiment.

    Science.gov (United States)

    Carino, Emily V; Kim, Hyun You; Henkelman, Graeme; Crooks, Richard M

    2012-03-07

    The voltammetry of Cu underpotential deposition (UPD) onto Pt dendrimer-encapsulated nanoparticles (DENs) containing an average of 147 Pt atoms (Pt(147)) is correlated to density functional theory (DFT) calculations. Specifically, the voltammetric peak positions are in good agreement with the calculated energies for Cu deposition and stripping on the Pt(100) and Pt(111) facets of the DENs. Partial Cu shells on Pt(147) are more stable on the Pt(100) facets, compared to the Pt(111) facets, and therefore, Cu UPD occurs on the 4-fold hollow sites of Pt(100) first. Finally, the structures of Pt DENs having full and partial monolayers of Cu were characterized in situ by X-ray absorption spectroscopy (XAS). The results of XAS studies are also in good agreement with the DFT-optimized models.

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

    Directory of Open Access Journals (Sweden)

    Anjali Sharma

    2015-09-01

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

  11. Biocompatible nanomaterials based on dendrimers, hydrogels and hydrogel nanocomposites for use in biomedicine

    Science.gov (United States)

    Khoa Nguyen, Cuu; Quyen Tran, Ngoc; Phuong Nguyen, Thi; Hai Nguyen, Dai

    2017-03-01

    Over the past decades, biopolymer-based nanomaterials have been developed to overcome the limitations of other macro- and micro- synthetic materials as well as the ever increasing demand for the new materials in nanotechnology, biotechnology, biomedicine and others. Owning to their high stability, biodegradability, low toxicity, and biocompatibility, biopolymer-based nanomaterials hold great promise for various biomedical applications. The pursuit of this review is to briefly describe our recent studies regarding biocompatible biopolymer-based nanomaterials, particularly in the form of dendrimers, hydrogels, and hydrogel composites along with the synthetic and modification approaches for the utilization in drug delivery, tissue engineering, and biomedical implants. Moreover, in vitro and in vivo studies for the toxicity evaluation are also discussed.

  12. 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

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

    DEFF Research Database (Denmark)

    Ficker, Mario

    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......Cardiovascular diseases are the leading causes of death world wide. The present IVUS and angiography techniques cannot suciently distinguish between stable atheromatous lesions and vulnerable plaques. Furthermore, the present cardiovascular drugs can only slow down the processes involved...... and excitation spectra within the biological window for in vivo imaging, which can be used for 2D near-infrared uorescence molecular imaging (2D-NIRF). Furthermore, the compounds expressed no detectable darktoxicity; however, radiation of the compound with light of the right wavelength (670 nm) triggered...

  14. 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.

  15. Study of linear and nonlinear optical properties of dendrimers using density matrix renormalization group method

    Science.gov (United States)

    Mukhopadhyay, S.; Ramasesha, S.

    2009-08-01

    We have used the density matrix renormalization group (DMRG) method to study the linear and nonlinear optical responses of first generation nitrogen based dendrimers with donor acceptor groups. We have employed Pariser-Parr-Pople Hamiltonian to model the interacting π electrons in these systems. Within the DMRG method we have used an innovative scheme to target excited states with large transition dipole to the ground state. This method reproduces exact optical gaps and polarization in systems where exact diagonalization of the Hamiltonian is possible. We have used a correction vector method which tacitly takes into account the contribution of all excited states, to obtain the ground state polarizibility, first hyperpolarizibility, and two photon absorption cross sections. We find that the lowest optical excitations as well as the lowest excited triplet states are localized. It is interesting to note that the first hyperpolarizibility saturates more rapidly with system size compared to linear polarizibility unlike that of linear polyenes.

  16. Study of linear and nonlinear optical properties of dendrimers using density matrix renormalization group method.

    Science.gov (United States)

    Mukhopadhyay, S; Ramasesha, S

    2009-08-21

    We have used the density matrix renormalization group (DMRG) method to study the linear and nonlinear optical responses of first generation nitrogen based dendrimers with donor acceptor groups. We have employed Pariser-Parr-Pople Hamiltonian to model the interacting pi electrons in these systems. Within the DMRG method we have used an innovative scheme to target excited states with large transition dipole to the ground state. This method reproduces exact optical gaps and polarization in systems where exact diagonalization of the Hamiltonian is possible. We have used a correction vector method which tacitly takes into account the contribution of all excited states, to obtain the ground state polarizibility, first hyperpolarizibility, and two photon absorption cross sections. We find that the lowest optical excitations as well as the lowest excited triplet states are localized. It is interesting to note that the first hyperpolarizibility saturates more rapidly with system size compared to linear polarizibility unlike that of linear polyenes.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. Highly sensitive dendrimer-based nanoplasmonic biosensor for drug allergy diagnosis.

    Science.gov (United States)

    Soler, Maria; Mesa-Antunez, Pablo; Estevez, M-Carmen; Ruiz-Sanchez, Antonio Jesus; Otte, Marinus A; Sepulveda, Borja; Collado, Daniel; Mayorga, Cristobalina; Torres, Maria Jose; Perez-Inestrosa, Ezequiel; Lechuga, Laura M

    2015-04-15

    A label-free biosensing strategy for amoxicillin (AX) allergy diagnosis based on the combination of novel dendrimer-based conjugates and a recently developed nanoplasmonic sensor technology is reported. Gold nanodisks were functionalized with a custom-designed thiol-ending-polyamido-based dendron (d-BAPAD) peripherally decorated with amoxicilloyl (AXO) groups (d-BAPAD-AXO) in order to detect specific IgE generated in patient's serum against this antibiotic during an allergy outbreak. This innovative strategy, which follows a simple one-step immobilization procedure, shows exceptional results in terms of sensitivity and robustness, leading to a highly-reproducible and long-term stable surface which allows achieving extremely low limits of detection. Moreover, the viability of this biosensor approach to analyze human biological samples has been demonstrated by directly analyzing and quantifying specific anti-AX antibodies in patient's serum without any sample pretreatment. An excellent limit of detection (LoD) of 0.6ng/mL (i.e. 0.25kU/L) has been achieved in the evaluation of clinical samples evidencing the potential of our nanoplasmonic biosensor as an advanced diagnostic tool to quickly identify allergic patients. The results have been compared and validated with a conventional clinical immunofluorescence assay (ImmunoCAP test), confirming an excellent correlation between both techniques. The combination of a novel compact nanoplasmonic platform and a dendrimer-based strategy provides a highly sensitive label free biosensor approach with over two times better detectability than conventional SPR. Both the biosensor device and the carrier structure hold great potential in clinical diagnosis for biomarker analysis in whole serum samples and other human biological samples.

  2. Dendrimer, liposomes, carbon nanotubes and PLGA nanoparticles: one platform assessment of drug delivery potential.

    Science.gov (United States)

    Mody, Nishi; Tekade, Rakesh Kumar; Mehra, Neelesh Kumar; Chopdey, Prashant; Jain, Narendra Kumar

    2014-04-01

    Liposomes (LIP), nanoparticles (NP), dendrimers (DEN), and carbon nanotubes (CNTs), represent eminent classes of drug delivery devices. A study was carried out herewith by employing docetaxel (DTX) as model drug to assess their comparative drug delivery potentials. Under optimized conditions, highest entrapment of DTX was observed in CNT-based formulation (DTX-CNTs, 74.70 ± 4.9%) followed by nanoparticles (DTX-NP, 62.34 ± 1.5%), liposome (49.2 ± 1.51%), and dendrimers (28.26 ± 1.74%). All the formulations were found to be of nanometric size. In vitro release studies were carried out in PBS (pH 7.0 and 4.0), wherein all the formulations showed biphasic release pattern. Cytotoxicity assay in human cervical cancer SiHa cells inferred lowest IC50 value of 1,235.09 ± 41.93 nM with DTX-CNTs, followed by DTX-DEN, DTX-LIP, DTX-NP with IC50 values of 1,571.22 ± 151.27, 1,653.98 ± 72.89, 1,922.75 ± 75.15 nM, respectively. Plain DTX showed higher hemolytic toxicity of 22.48 ± 0.94%, however loading of DTX inside nanocarriers drastically reduced its hemolytic toxicity (DTX-DEN, 17.22 ± 0.48%; DTX-LIP, 4.13 ± 0.19%; DTX-NP, 6.43 ± 0.44%; DTX-CNTs, 14.87 ± 1.69%).

  3. Preparation, Radiolabelling and Biodistribution Study of ~(177)Lu-DTPA-G3

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Polyamidoamine (PAMAM) dendrimers are new artificial macromolecules with tree-like structure and have characteristics of greater water-solubility, bioavailability and compatibility. It can be carried by the drug molecules. PAMAM have been

  4. 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.

  5. 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.

  6. 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

  7. 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.

  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. Advancements in Anion Exchange Membrane Cations

    Energy Technology Data Exchange (ETDEWEB)

    Sturgeon, Matthew R. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Long, Hai [National Renewable Energy Lab. (NREL), Golden, CO (United States); Park, Andrew M. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Pivovar, Bryan S. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2015-10-15

    Anion-exchange membrane fuel cells (AME-FCs) are of increasingly popular interest as they enable the use of non-Pt fuel cell catalysts, the primary cost limitation of proton exchange membrane fuel cells. Benzyltrimethyl ammonium (BTMA) is the standard cation that has historically been utilized as the hydroxide conductor in AEMs. Herein we approach AEMs from two directions. First and foremost we study the stability of several different cations in a hydroxide solution at elevated temperatures. We specifically targeted BTMA and methoxy and nitro substituted BTMA. We've also studied the effects of adding an akyl spacer units between the ammonium cation and the phenyl group. In the second approach we use computational studies to predict stable ammonium cations, which are then synthesized and tested for stability. Our unique method to study cation stability in caustic conditions at elevated temperatures utilizes Teflon Parr reactors suitable for use under various temperatures and cation concentrations. NMR analysis was used to determine remaining cation concentrations at specific time points with GCMS analysis verifying product distribution. We then compare the experimental results with calculated modeling stabilities. Our studies show that the electron donating methoxy groups slightly increase stability (compared to that of BTMA), while the electron withdrawing nitro groups greatly decrease stability in base. These results give insight into possible linking strategies to be employed when tethering a BTMA like ammonium cation to a polymeric backbone; thus synthesizing an anion exchange membrane.

  10. Cation diffusion in the natural zeolite clinoptilolite

    Energy Technology Data Exchange (ETDEWEB)

    Dyer, A.; White, K.J. [Science Research Institute, Chemistry Division, Cockcroft Building, University of Salford, Salford (United Kingdom)

    1999-12-14

    The natural zeolite clinoptilolite is mined commercially in many parts of the world. It is a selective exchanger for the ammonium cation and this has prompted its use in waste water treatment, swimming pools and in fish farming. It is also used to scavenge radioisotopes in nuclear waste clean-up. Further potential uses for clinoptilolite are in soil amendment and remediation. The work described herein provides thermodynamic data on cation exchange processes in clinoptilolite involving the NH{sub 4}, Na, K, Ca, and Mg cations. The data includes estimates of interdiffusion coefficients together with free energies, entropies and energies of activation for the cation exchanges studied. Suggestions are made as to the mechanisms of cation-exchanges involved.

  11. Facile synthesis of dendrimer-like star-branched poly(isopropylacrylamide) via combination of click chemistry and atom transfer radical polymerization

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    We report a facile synthesis method of dendrimer-like star-branched poly(N-isopropylacrylamide) (PNIPAM) via the combination of click chemistry and atom transfer radical polymerization (ATRP) by employing the arm-first approach.First,the α-azido-ω-chloro-heterodifunctionalized building block,N3-PNIPAM-Cl (G0-Cl),was synthesized via ATRP by 3-azidopropyl 2-chloropropionate as the initiator.Taking advantage of click chemistry,the first generation (G1) of dendrimer-like star-branched PNIPAM,G1-(Cl)3,was facilely prepared via the click coupling reaction between G0-Cl and tripropargylamine.For the construction of second generation (G2) dendrimer-like star-branched PNIPAM,G2-(Cl)6,terminal chloride moieties of G1-(Cl)3 were first converted to azide,and then reacted with excess tripropargylamine to give G1-(alkynyl)6 ;G2-(Cl)6 was subsequently prepared via click reaction between G1-(alkynyl) 6 and G0-Cl.Gel permeation chromatography (GPC) and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry were employed to confirm the successful construction of dendrimer-like star-branched polymers.The unique thermal phase transition behavior of this dendrimer-like star-branched polymer in aqueous solutions was further investigated by turbidimetry and micro-differential scanning calorimetry (Micro-DSC).

  12. 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.

  13. Cation distributions on rapidly solidified cobalt ferrite

    Science.gov (United States)

    De Guire, Mark R.; Kalonji, Gretchen; O'Handley, Robert C.

    1990-01-01

    The cation distributions in two rapidly solidified cobalt ferrites have been determined using Moessbauer spectroscopy at 4.2 K in an 8-T magnetic field. The samples were obtained by gas atomization of a Co0-Fe2O3-P2O5 melt. The degree of cation disorder in both cases was greater than is obtainable by cooling unmelted cobalt ferrite. The more rapidly cooled sample exhibited a smaller departure from the equilibrium cation distribution than did the more slowly cooled sample. This result is explained on the basis of two competing effects of rapid solidification: high cooling rate of the solid, and large undercooling.

  14. Dendrimer-templated Pd nanoparticles and Pd nanoparticles synthesized by reverse microemulsions as efficient nanocatalysts for the Heck reaction: A comparative study.

    Science.gov (United States)

    Noh, Ji-Hyang; Meijboom, Reinout

    2014-02-01

    Palladium nanoparticles (NPs) were prepared using a dendrimer-templated method using G4, G5 and G6 PAMAM-OH dendrimers as well as a reverse microemulsion method using the water/dioctyl sulfosuccinate sodium salt (aerosol-OT, AOT) surfactant/isooctane system with water to surfactant ratios (ω0) of 5, 10 and 13. These 6 catalysts were characterized by UV-Vis spectroscopy, TEM, EDX, and XRD. TEM micrographs showed that the average sizes of 2.74-3.32nm with narrower size distribution were achieved by using dendrimer-templated synthetic methods, whereas the reverse microemulsion method resulted in broad size distribution with an average size of 3.87-5.06nm. The influence of various reaction parameters such as base, catalyst dosing, alkene, aryl halide and temperature on the Heck C-C coupling reaction was evaluated. The activation parameters were derived from the reaction rate of each catalyst obtained at various temperatures. A correlation of catalytic activity, enthalpy of activation and particle size is discussed. Particle size changes of each catalyst were investigated after the catalytic reaction. Overall results indicated that dendrimer-templated Pd NP catalysts showed superior activity as compared to the Pd NPs synthesized by reverse microemulsions, with the dendrimer-templated G5-OH(Pd80) showing the best activity. These catalysts were also reusable for 3 cycles, retaining high yield and showing excellent yields under mild conditions. Therefore, the dendrimer-templated Pd NPs are efficient catalyst systems for the ligand-free Heck C-C coupling reaction.

  15. First generation TREN dendrimers functionalized with naphthyl and/or dansyl units. Ground and excited state electronic interactions and protonation effects.

    Science.gov (United States)

    Passaniti, Paolo; Maestri, Mauro; Ceroni, Paola; Bergamini, Giacomo; Vögtle, Fritz; Fakhrnabavi, Hassan; Lukin, Oleg

    2007-04-01

    We report the photophysical properties (absorption and emission spectra, quantum yield, and lifetime) of five dendrimers of first generation based on a TREN (tris(2-aminoethyl)amine) skeleton functionalized at the periphery with naphthyl and/or 5-dimethylamino-1-naphthalenesulfonamide (hereafter called dansyl) chromophores. Each dendrimer comprises one tertiary amine unit in the core and three branches carrying a sulfonimido unit at the periphery, each one substituted by two identical or different moieties. In particular, TD6 and TN6 contain dansyl (D) or naphthyl (N) units, respectively, while TD3B3, TN3B3 and TN3D3 contain dansyl, naphthyl or benzyl (B) units at the periphery. The spectroscopic behaviour of these dendrimers has been investigated in acetonitrile solution and compared with that of reference compounds. For all dendrimers the absorption bands are red shifted compared to those of monomeric naphthyl and dansyl reference compounds. Moreover, the intense naphthyl and dansyl fluorescence is greatly quenched because of strong interactions between the two aromatic moieties linked by a sulfonimido unit. Protonation of the amine units of the dendrimers by addition of CF(3)SO(3)H (triflic) acid causes a decrease in intensity of the luminescence and a change in the shape of the emission bands. The shapes of the titration curves depend on the dendrimer, but in any case the effect of acid can be fully reversed by successive addition of base (tributylamine). The obtained results reveal that among the intradendrimer interactions the most important one is that taking place (via mesomeric interaction) between the various chromophores and a pair of sulfonimido groups.

  16. Dendrimer-like alpha-d-glucan nanoparticles activate dendritic cells and are effective vaccine adjuvants.

    Science.gov (United States)

    Lu, Fangjia; Mencia, Alejandra; Bi, Lin; Taylor, Aaron; Yao, Yuan; HogenEsch, Harm

    2015-04-28

    The use of nanoparticles for delivery of vaccine antigens and as vaccine adjuvants is appealing because their size allows efficient uptake by dendritic cells and their biological properties can be tailored to the desired function. Here, we report the effect of chemically modified phytoglycogen, a dendrimer-like α-d-glucan nanoparticle, on dendritic cells in vitro, and the utility of this type of nanoparticle as a vaccine adjuvant in vivo. The modified phytoglycogen nanoparticle, termed Nano-11, has a positive surface charge which enabled electrostatic adsorption of negatively charged protein antigens. The Nano-11-antigen complexes were efficiently phagocytized by dendritic cells. Nano-11 induced increased expression of costimulatory molecules and the secretion of IL-1β and IL-12p40 by dendritic cells. Intramuscular injection of Nano-11-antigen formulations induced a significantly enhanced immune response to two different protein antigens. Examination of the injection site revealed numerous monocytes and relatively few neutrophils at one day after injection. The inflammation had nearly completely disappeared by 2 weeks after injection. These studies indicate that Nano-11 is an effective vaccine delivery vehicle that significantly enhances the immune response. This type of plant based nanoparticle is considered highly cost-effective compared with fully synthetic nanoparticles and appears to have an excellent safety profile making them an attractive adjuvant candidate for prophylactic vaccines.

  17. Effects of dopamine concentration on energy transfer between dendrimer-QD and dye-labeled antibody

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ki Rahm [Department of Chemical and Bio Engineering, Kyungwon University, Bokjung-dong, Sujung-gu, Sungnam-shi, Gyunggi-do 461-701 (Korea, Republic of); Kang, Ik-Joong, E-mail: ijkang@kyungwon.ac.kr [Department of Chemical and Bio Engineering, Kyungwon University, Bokjung-dong, Sujung-gu, Sungnam-shi, Gyunggi-do 461-701 (Korea, Republic of)

    2009-07-15

    The Unified Parkinson's Disease Rating Scale (UPDRS) is currently used to assess Parkinson's disease, and is a key method for determining the progression of disease based on the gross findings of patients. However, this method cannot quantify the extent of disease of patients, which means the administration of drugs cannot be determined on a real-time basis. Thalamotomy also causes discomfort and pain to the patients, and adversely affects treatment as it is performed following the onset of symptoms. Accordingly, the dopamine concentration, which is one of the key factors in determining this disease, needs to be detected quantitatively at ordinary times. Hence, the development of a bio-kit or a bio-sensor is essential for effectively prescribing the correct dopamine concentration in a customizable manner. In this study, the effect of dopamine level on this phenomenon was observed using the Forster resonance energy transfer (FRET) phenomenon generated between a donor and acceptor. By confirming the photoluminescence (PL) and lifetime data, it was demonstrated that the degree of energy transfer increased with increasing dopamine concentration. To apply this phenomenon to an optical sensor, a glass surface was modified with a quantum dot (QD)-encapsulated dendrimer, and analyzed using the contact angle and ATR-FTIR. The topology of surface was determined by an atomic force microscope (AFM).

  18. Zirconia-poly(propylene imine) dendrimer nanocomposite based electrochemical urea biosensor.

    Science.gov (United States)

    Shukla, Sudheesh K; Mishra, Ajay K; Mamba, Bhekie B; Arotiba, Omotayo A

    2014-11-01

    In this article we report a selective urea electrochemical biosensor based on electro-co-deposited zirconia-polypropylene imine dendrimer (ZrO2-PPI) nanocomposite modified screen printed carbon electrode (SPCE). ZrO2 nanoparticles, prepared by modified sol-gel method were dispersed in PPI solution, and electro-co-deposited by cyclic voltammetry onto a SPCE surface. The material and the modified electrodes were characterised using FTIR, electron microscopy and electrochemistry. The synergistic effect of the high active surface area of both materials, i.e. PPI and ZrO2 nanoparticles, gave rise to a remarkable improvement in the electrocatalytic properties of the biosensor and aided the immobilisation of the urease enzyme. The biosensor has an ampereometric response time of ∼4 s in urea concentration ranging from 0.01 mM to 2.99 mM with a correlation coefficient of 0.9985 and sensitivity of 3.89 μA mM(-1) cm(-2). The biosensor was selective in the presence of interferences. Photochemical study of the immobilised enzyme revealed high stability and reactivity.

  19. Dendrimer-like assemblies based on organoclays as multi-host system for sustained drug delivery.

    Science.gov (United States)

    Li, Wei; Sun, Lili; Pan, Lijun; Lan, Zuopin; Jiang, Tao; Yang, Xiaolan; Luo, Jianchun; Li, Ronghua; Tan, Liqing; Zhang, Shurong; Yu, Mingan

    2014-11-01

    Chemical modification of nanoclay will ensure further progress on these materials. In this work, we show that montmorillonite (MTM) nanosheets can be modified with β-cyclodextrin (CD) via a nucleophilic substitution reaction between mono-6-(p-toluenesulfonyl)-6-deoxy-β-CD and an amino group of 3-aminopropyltriethoxysilane (APTES)-functionalized MTM. The resulting MTM-APTES-CD can be further self-assembled into dendrimer-like assemblies, exhibit a well-dispersed property even in Dulbecco's phosphate-buffered saline and do not aggregate for a period of at least 20days. The structure, morphology and assembly mechanism are systematically studied by (29)Si MAS NMR, FT-IR, (1)H NMR, SEM, FE-TEM, DLS and AFM, and the change in assemblies during the drug release is monitored using FE-TEM images. MTT assays indicate that the assemblies only have low cytotoxicity, while CLSM and TEM observations reveal that the assemblies can easily penetrate cultured human endothelial cells. When clopidogrel is used as a guest molecule, the assemblies show not only much higher loading capacities compared to MTM and other containing β-CD assemblies or nanoparticles, but also a sustained release of clopidogrel up to 30days. This is attributed to the fact that the guest molecule is both supramolecularly complexed within the dendritic scaffold and intercalated into CD and MTM hosts. Host-guest systems between assemblies and various guests hold promising applications in drug delivery system and in the biomedical fields.

  20. Detection of parathyroid hormone using an electrochemical impedance biosensor based on PAMAM dendrimers.

    Science.gov (United States)

    Özcan, Hakkı Mevlüt; Sezgintürk, Mustafa Kemal

    2015-01-01

    This paper presents a novel hormone-based impedimetric biosensor to determine parathyroid hormone (PTH) level in serum for diagnosis and monitoring treatment of hyperparathyroidism, hypoparathyroidism and thyroid cancer. The interaction between PTH and the biosensor was investigated by an electrochemical method. The biosensor was based on the gold electrode modified by 12-mercapto dodecanoic (12MDDA). Antiparathyroid hormone (anti-PTH) was covalently immobilized on to poly amidoamine dendrimer (PAMAM) which was bound to a 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide/N-hydroxysuccinimide (EDC/NHS) couple, self-assembled monolayer structure from one of the other NH2 sites. The immobilization of anti-PTH was monitored by electrochemical impedance spectroscopy, cyclic voltammetry and scanning electron microscope techniques. After the optimization studies of immobilization materials such as 12MDDA, EDC-NHS, PAMAM, and glutaraldehyde, the performance of the biosensor was investigated in terms of linearity, sensitivity, repeatability, and reproducibility. PTH was detected within a linear range of 10-60 fg/mL. Finally the described biosensor was used to monitor PTH levels in artificial serum samples.

  1. Spontaneous Formation of Lipid Nanotubes and Lipid Nanofibers from Giant Charged Dendrimer Lipids

    Science.gov (United States)

    Zidovska, Alexandra; Ewert, Kai K.; Safinya, Cyrus R.; Quispe, Joel; Carragher, Bridgett; Potter, Clinton S.

    2007-03-01

    Liposomes have attracted much scientific interest due to their applications in model cells studies and in drug encapsulation. We report on the discovery of new vesicle phases formed in mixtures of MVLBG2, DOPC and water. MVLBG2 is a newly synthesized highly charged (16+) lipid (K. Ewert et al., JACS, 2006) with giant dendrimer headgroup thus leading to a high spontaneous curvature of the molecule. In combination with zero-curvature DOPC, MVLBG2 exhibits a rich phase diagram showing novel vesicle morphologies such as bones, lipid nanotubes and nanofibers as revealed by differential contrast microscopy (DIC) and cryo-TEM. At the micron scale DIC reveals a new phase consisting of bone-like vesicles. This novel morphology persists down to the nanometer scale as shown by cryo-TEM. The nanotubes are of diameter 10-50 nm, length > 1μm and consist of a single lipid bilayer. A surprising new morphology arises resulting from a spontaneous topological transition from tubes to lipid nanorods. Funded by DOE DE-FG-02-06ER46314, NIH GM-59288, NSF DMR-0503347.

  2. Cationic ruthenium alkylidene catalysts bearing phosphine ligands.

    Science.gov (United States)

    Endo, Koji; Grubbs, Robert H

    2016-02-28

    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 bearing bulky phosphine ligands. Simple ligand exchange using silver(i) salts of non-coordinating or weakly coordinating anions provided either PPh3 or chelating Ph2P(CH2)nPPh2 (n = 2 or 3) ligated cationic catalysts. The structures of these newly reported catalysts feature unique geometries caused by ligation of the bulky phosphine ligands. Their activities and selectivities in standard metathesis reactions were also investigated. These cationic ruthenium alkylidene catalysts reported here showed moderate activity and very similar stereoselectivity when compared to the second generation ruthenium dichloride catalyst in ring-closing metathesis, cross metathesis, and ring-opening metathesis polymerization assays.

  3. 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

  4. Cationized Carbohydrate Gas-Phase Fragmentation Chemistry

    Science.gov (United States)

    Bythell, Benjamin J.; Abutokaikah, Maha T.; Wagoner, Ashley R.; Guan, Shanshan; Rabus, Jordan M.

    2016-11-01

    We investigate the fragmentation chemistry of cationized carbohydrates using a combination of tandem mass spectrometry, regioselective labeling, and computational methods. Our model system is D-lactose. Barriers to the fundamental glyosidic bond cleavage reactions, neutral loss pathways, and structurally informative cross-ring cleavages are investigated. The most energetically favorable conformations of cationized D-lactose were found to be similar. In agreement with the literature, larger group I cations result in structures with increased cation coordination number which require greater collision energy to dissociate. In contrast with earlier proposals, the B n -Y m fragmentation pathways of both protonated and sodium-cationized analytes proceed via protonation of the glycosidic oxygen with concerted glycosidic bond cleavage. Additionally, for the sodiated congeners our calculations support sodiated 1,6-anhydrogalactose B n ion structures, unlike the preceding literature. This affects the subsequent propensity of formation and prediction of B n /Y m branching ratio. The nature of the anomeric center (α/β) affects the relative energies of these processes, but not the overall ranking. Low-energy cross-ring cleavages are observed for the metal-cationized analytes with a retro-aldol mechanism producing the 0,2 A 2 ion from the sodiated forms. Theory and experiment support the importance of consecutive fragmentation processes, particularly for the protonated congeners at higher collision energies.

  5. 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.

  6. 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.

  7. Divalent cation shrinks DNA but inhibits its compaction with trivalent cation

    Science.gov (United States)

    Tongu, Chika; Kenmotsu, Takahiro; Yoshikawa, Yuko; Zinchenko, Anatoly; Chen, Ning; Yoshikawa, Kenichi

    2016-05-01

    Our observation reveals the effects of divalent and trivalent cations on the higher-order structure of giant DNA (T4 DNA 166 kbp) by fluorescence microscopy. It was found that divalent cations, Mg(2+) and Ca(2+), inhibit DNA compaction induced by a trivalent cation, spermidine (SPD(3+)). On the other hand, in the absence of SPD(3+), divalent cations cause the shrinkage of DNA. As the control experiment, we have confirmed the minimum effect of monovalent cation, Na(+) on the DNA higher-order structure. We interpret the competition between 2+ and 3+ cations in terms of the change in the translational entropy of the counterions. For the compaction with SPD(3+), we consider the increase in translational entropy due to the ion-exchange of the intrinsic monovalent cations condensing on a highly charged polyelectrolyte, double-stranded DNA, by the 3+ cations. In contrast, the presence of 2+ cation decreases the gain of entropy contribution by the ion-exchange between monovalent and 3+ ions.

  8. Characterization of Pt@Cu Core@Shell Dendrimer-Encapsulated Nanoparticles Synthesized by Cu Underpotential Deposition

    Energy Technology Data Exchange (ETDEWEB)

    E Carino; R Crooks

    2011-12-31

    Dendrimer-encapsulated nanoparticles (DENs) containing averages of 55, 147, and 225 Pt atoms immobilized on glassy carbon electrodes served as the electroactive surface for the underpotential deposition (UPD) of a Cu monolayer. This results in formation of core@shell (Pt@Cu) DENs. Evidence for this conclusion comes from cyclic voltammetry, which shows that the Pt core DENs catalyze the hydrogen evolution reaction before Cu UPD, but that after Cu UPD this reaction is inhibited. Results obtained by in situ electrochemical X-ray absorption spectroscopy (XAS) confirm this finding.

  9. Characterization of Pt@Cu core@shell dendrimer-encapsulated nanoparticles synthesized by Cu underpotential deposition.

    Science.gov (United States)

    Carino, Emily V; Crooks, Richard M

    2011-04-05

    Dendrimer-encapsulated nanoparticles (DENs) containing averages of 55, 147, and 225 Pt atoms immobilized on glassy carbon electrodes served as the electroactive surface for the underpotential deposition (UPD) of a Cu monolayer. This results in formation of core@shell (Pt@Cu) DENs. Evidence for this conclusion comes from cyclic voltammetry, which shows that the Pt core DENs catalyze the hydrogen evolution reaction before Cu UPD, but that after Cu UPD this reaction is inhibited. Results obtained by in situ electrochemical X-ray absorption spectroscopy (XAS) confirm this finding.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Adsorption of precious metals in water by dendrimer modified magnetic nanoparticles.

    Science.gov (United States)

    Yen, Chia-Hsin; Lien, Hsing-Lung; Chung, Jung-Shing; Yeh, Hund-Der

    2017-01-15

    Magnetic nanoparticles modified by third-generation dendrimers (MNP-G3) and MNP-G3 further modified by ethylenediaminetetraacetic acid (EDTA) (MNP-G3-EDTA) were conducted to investigate their ability for recovery of precious metals (Pd(IV), Au(III), Pd(II) and Ag(I)) in water. Experiments were carried out using batch reactors for the studies of adsorption kinetics, adsorption isotherms, competitive adsorption and regeneration. The pseudo second-order model is the best-fit model among others suggesting that the adsorption of precious metals by MNP-G3 in water is a chemisorption process. Three adsorption isotherms namely Langmuir, Freundlich and Dubinin-Radushkevich isotherm were examined and the results showed the similarities and consistency of both linear and nonlinear analyses. Pd(IV) and Au(III) with higher valence exhibited relatively better adsorption efficiency than Pd(II) and Ag(I) with lower valence suggesting that the adsorption of precious metals by MNP-G3 is a function of valence. In the presence of the competing ion Zn(II), the adsorption efficiency of MNP-G3 for all four precious metals was declined significantly. The use of MNP-G3-EDTA revealed an increase in the adsorption efficiency for all four precious metals. However, the low selectivity of MNP-G3 towards precious metals was not enhanced by the modification of EDTA onto the MNP-G3. The regeneration of metal-laden MNP-G3 can be readily performed by using 1.0% HCl solution as a desorbent solution.

  15. 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

    work we have quantified the binding constants for the host-guest interactions between two different host motifs and six different guest molecules. The host molecules, which resemble the periphery of a poly(propylene imine) dendrimer, have been fitted with an anthracene-based fluorescent probe. The two...

  16. 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

  17. Self-assembled and covalently linked capillary coating of diazoresin and cyclodextrin-derived dendrimer for analysis of proteins by capillary electrophoresis.

    Science.gov (United States)

    Yu, Bing; Chi, Ming; Han, Yuxing; Cong, Hailin; Tang, Jianbin; Peng, Qiaohong

    2016-05-15

    Self-assembled and covalently linked capillary coatings of cyclodextrin-derived (CD) dendrimer were prepared using photosensitive diazoresin (DR) as a coupling agent. Layer by layer (LBL) self-assembled DR/CD-dendrimer coatings based on ionic bonding was fabricated first on the inner surface of capillary, and subsequently converted into covalent bonding after treatment with UV light through a unique photochemistry reaction of DR. Protein adsorption on the inner surface of capillary was suppressed by the DR/CD-dendrimer coating, and thus a baseline separation of lysozyme (Lys), myoglobin (Mb), bovine serum albumin (BSA) and ribonuclease A (RNase A) was achieved using capillary electrophoresis (CE). Compared with the bare capillary, the DR/CD-dendrimer covalently linked capillary coatings showed excellent protein separation performance with good stability and repeatability. Because of the replacement of highly toxic and moisture sensitive silane coupling agent by DR in the covalent coating preparation, this method may provide an environmentally friendly and simple way to prepare the covalently coated capillaries for CE.

  18. Immobilization of trypsin on water-soluble dendrimer-modified carbon nanotubes for on-plate proteolysis combined with MALDI-MS analysis.

    Science.gov (United States)

    Zhang, Ying; Cao, Weiman; Liu, Minbo; Yang, Shiping; Wu, Huixia; Lu, Haojie; Yang, Pengyuan

    2010-08-01

    A novel on-plate digestion method combined with MALDI-MS analysis is reported, using trypsin-linked dendrimer-modified carbon nanotubes (dCNTs) as the enzyme immobilization probe. Excellent digestion performance was achieved in a short time without any complicated reduction and alkylation procedures.

  19. Peptide-derivatized SB105-A10 dendrimer inhibits the infectivity of R5 and X4 HIV-1 strains in primary PBMCs and cervicovaginal histocultures.

    Directory of Open Access Journals (Sweden)

    Isabella Bon

    Full Text Available Peptide dendrimers are a class of molecules that exhibit a large array of biological effects including antiviral activity. In this report, we analyzed the antiviral activity of the peptide-derivatized SB105-A10 dendrimer, which is a tetra-branched dendrimer synthetized on a lysine core, in activated peripheral blood mononuclear cells (P