Analysis of Biotinylated Generation 4 Poly(amidoamine (PAMAM Dendrimer Distribution in the Rat Brain and Toxicity in a Cellular Model of the Blood-Brain Barrier

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Heather A. Bullen

2013-09-01

Full Text Available Dendrimers are highly customizable nanopolymers with qualities that make them ideal for drug delivery. The high binding affinity of biotin/avidin provides a useful approach to fluorescently label synthesized dendrimer-conjugates in cells and tissues. In addition, biotin may facilitate delivery of dendrimers through the blood-brain barrier (BBB via carrier-mediated endocytosis. The purpose of this research was to: (1 measure toxicity using lactate dehydrogenase (LDH assays of generation (G4 biotinylated and non-biotinylated poly(amidoamine (PAMAM dendrimers in a co-culture model of the BBB, (2 determine distribution of dendrimers in the rat brain, kidney, and liver following systemic administration of dendrimers, and (3 conduct atomic force microscopy (AFM on rat brain sections following systemic administration of dendrimers. LDH measurements showed that biotinylated dendrimers were toxic to cell co-culture after 48 h of treatment. Distribution studies showed evidence of biotinylated and non-biotinylated PAMAM dendrimers in brain. AFM studies showed evidence of dendrimers only in brain tissue of treated rats. These results indicate that biotinylation does not decrease toxicity associated with PAMAM dendrimers and that biotinylated PAMAM dendrimers distribute in the brain. Furthermore, this article provides evidence of nanoparticles in brain tissue following systemic administration of nanoparticles supported by both fluorescence microscopy and AFM.

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

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

2014-05-27

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

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

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

2009-08-19

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

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.

Low-Level Detection of Poly(amidoamine) PAMAM Dendrimers Using Immunoimaging Scanning Probe Microscopy

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Cason, Chevelle A.; Fabré, Thomas A.; Buhrlage, Andrew; Haik, Kristi L.; Bullen, Heather A.

2012-01-01

Immunoimaging scanning probe microscopy was utilized for the low-level detection and quantification of biotinylated G4 poly(amidoamine) PAMAM dendrimers. Results were compared to those of high-performance liquid chromatography (HPLC) and found to provide a vastly improved analytical method for the low-level detection of dendrimers, improving the limit of detection by a factor of 1000 (LOD = 2.5 × 10−13 moles). The biorecognition method is reproducible and shows high specificity and good accur...

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

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Saghir Akhtar

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

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

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

2000-03-01

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

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

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

2008-11-01

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

Aqueous poly(amidoamine) dendrimer G3 and G4 generations with several interior cores at pHs 5 and 7: a molecular dynamics simulation study.

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Kavyani, Sajjad; Amjad-Iranagh, Sepideh; Modarress, Hamid

2014-03-27

Poly(amidoamine) (PAMAM) dendrimers play an important role in drug delivery systems, because the dendrimers are susceptible to gain unique features with modification of their structure such as changing their terminals or improving their interior core. To investigate the core improvement and the effect of core nature on PAMAM dendrimers, we studied two generations G3 and G4 PAMAM dendrimers with the interior cores of commonly used ethylendiamine (EDA), 1,5-diaminohexane (DAH), and bis(3-aminopropyl) ether (BAPE) solvated in water, as an aqueous dendrimer system, by using molecular dynamics simulation and applying a coarse-grained (CG) dendrimer force field. To consider the electrostatic interactions, the simulations were performed at two protonation states, pHs 5 and 7. The results indicated that the core improvement of PAMAM dendrimers with DAH produces the largest size for G3 and G4 dendrimers at both pHs 5 and 7. The increase in the size was also observed for BAPE core but it was not so significant as that for DAH core. By considering the internal structure of dendrimers, it was found that PAMAM dendrimer shell with DAH core had more cavities than with BAPE core at both pHs 5 and 7. Also the moment of inertia calculations showed that the generation G3 is more open-shaped and has higher structural asymmetry than the generation G4. Possessing these properties by G3, specially due to its structural asymmetry, make penetration of water beads into the dendrimer feasible. But for higher generation G4 with its relatively structural symmetry, the encapsulation efficiency for water molecules can be enhanced by changing its core to DAH or BAPE. It is also observed that for the higher generation G4 the effect of core modification is more profound than G3 because the core modification promotes the structural asymmetry development of G4 more significantly. Comparing the number of water beads that penetrate into the PAMAM dendrimers for EDA, DAH, and BAPE cores indicates a

Dendrimers for Drug Delivery

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Abhay Singh Chauhan

2018-04-01

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

Understanding the sorption behavior of Pu{sup 4+} on poly(amidoamine) dendrimer functionalized carbon nanotube. Sorption equilibrium, mechanism, kinetics, radiolytic stability, and back-extraction studies

Energy Technology Data Exchange (ETDEWEB)

Kumar, Parveen [Indian Institute of Technology, Himachal Pradesh (India); Sengupta, Arijit [Bahbha Atomic Research Centre, Mumbai (India). Radiochemistry Div.; Deb, Ashish Kumar Singha; Ali, S. Musharaf [Bahbha Atomic Research Centre, Mumbai (India). Chemical Engineering Div.; Homi Bhabha National Institute, Mumbai (India); Dasgupta, Kinshuk [Bhabha National Institute, Mumbai (India). Mechanical Metallurgy Div.

2017-07-01

Poly(amidoamine) dendrimer functionalized carbon nanotube was demonstrated as highly efficient sorbent of the Pu{sup 4+} from radioactive waste solution. The second generation dendrimer was found to have more efficiency as compared to the 1{sup st} generation might be due to the availability of more functionality for coordinating to the Pu{sup 4+} ion. Analysis of different isotherm models revealed that, Langmuir isotherm was predominantly operating through chemi-sorption (with the sorption energy 10.07 and 16.95 kJ mol{sup -1} for 1{sup st} and 2{sup nd} generation dendrimer) with the sorption capacity 89.22 mg g{sup -1} and 92.48 mg g{sup -1} for 1{sup st} and 2{sup nd} generation dendrimer, respectively. Analysis of different sorption kinetics model revealed that the sorption proceeded via pseudo 2{sup nd} order reaction. The 2{sup nd} generation dendrimer was found to be radiolytically more stable while oxalic acid was found to be suitable for quantitative back extraction of Pu{sup 4+}.

Binding of poly(amidoamine), carbosilane, phosphorus and hybrid dendrimers to thrombin-Constants and mechanisms.

Science.gov (United States)

Shcharbin, Dzmitry; Pedziwiatr-Werbicka, Elzbieta; Vcherashniaya, Aliaksandra; Janaszewska, Anna; Marcinkowska, Monika; Goska, Piotr; Klajnert-Maculewicz, Barbara; Ionov, Maksim; Abashkin, Viktar; Ihnatsyeu-Kachan, Aliaksei; de la Mata, F Javier; Ortega, Paula; Gomez-Ramirez, Rafael; Majoral, Jean-Pierre; Bryszewska, Maria

2017-07-01

Thrombin is an essential part of the blood coagulation system; it is a serine protease that converts soluble fibrinogen into insoluble strands of fibrin, and catalyzes many other coagulation-related reactions. Absorption at its surface of small nanoparticles can completely change the biological properties of thrombin. We have analyzed the influence on thrombin of 3 different kinds of small nanoparticles: dendrimers (phosphorus-based, carbosilane based and polyamidoamine) and 2 hybrid systems containing carbosilane, viologen and phosphorus dendritic scaffolds in one single molecule, bearing different flexibility, size and surface charge. There was significant alteration in the rigidity of the rigid dendrimers in contrast to flexible dendrimers. These differences in their action are important in understanding interactions taking place at a bio-nanointerface. Copyright © 2017 Elsevier B.V. All rights reserved.

Photophysical property of rhodamine-cored poly(amidoamine) dendrimers: Simultaneous effect of spirolactam ring-opening and PET process on sensing trivalent chromium ion

International Nuclear Information System (INIS)

Lei Yonglin; Su Yuanqiang; Huo Jichuan

2011-01-01

Two novel poly(amidoamine) (PAMAM) dendrimers, comprising rhodamine B unit in the core and 1-phenyl-3-methyl-5-pyrazolone unit at the periphery, have been synthesized and characterized. Both dendrimers displayed high selectivity and sensitivity towards Cr 3+ ion. As considering the potential of being applied as fluorescent sensors for Cr 3+ ion, we studied the complexes formed between the dendrimers and Cr 3+ ion. Different PAMAM dendrimers had different recognition mechanism towards Cr 3+ ion. For dendrimer G2, the recognition of Cr 3+ was mainly due to the ring-opening of spirolactam. However, it significantly depended on the simultaneous effect of ring-opening of spirolactam and photoinduced electron transfer (PET) in the case of dendrimer G3. - Highlights: → First synthesize two novel PAMAM simultaneously containing rhodamine and pyrazolone. → Novel dendrimer show high selectivity and sensitivity towards Cr 3+ . → Recognition Cr 3+ of dendrimer G2 is dominantly due to the ring-opening mechanism. → Sensing Cr 3+ of dendrimer G3 is dependent on simultaneous mechanisms of ring-opening and PET.

para-Sulfonatocalix[4]arene and polyamidoamine dendrimer nanocomplexes as delivery vehicles for a novel platinum anticancer agent.

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Pang, Chi Ting; Ammit, Alaina J; Ong, Yu Qing Elysia; Wheate, Nial J

2017-11-01

Novel para-sulfonatocalix[4]arene (sCX[4]) and polyamidoamine (PAMAM) dendrimer nanocomplexes were evaluated as delivery vehicles for the platinum anticancer agent [(1,10-phenanthroline)(1S,2S-diaminocyclohexane)platinum(II)] chloride (PHENSS). Different ratios of sCX[4] to PHENSS were tested for their compatibility, with a ratio of 6:1 sCX[4]:PHENSS having the best solubility. The loading of sCX[4], and sCX[4]-bound PHENSS, onto three different generations of PAMAM dendrimers (G3.0-5.0) was examined using UV-visible spectrophotometry. The quantity of sCX[4] bound was found to increase exponentially with dendrimer size: G3, 15 sCX[4] molecules per dendrimer; G4, 37; and G5, 78. Similarly, the loading of sCX[4]-bound PHENSS also increased with increasing dendrimer size: G3, 7 PHENSS molecules per dendrimer; G4, 14; and G5, 28.5. The loading of sCX[4]-bound PHENSS molecules is significantly lower when compared with that of sCX[4], which indicates that less than half of the binding sites were occupied (45, 44, and 44%, respectively). By 1 H NMR and UV-vis analysis, the nanocomplex was found to be stable in NaCl solutions at concentrations up to 150mM. While PHENSS is more active in vitro than cisplatin against the human breast cancer cell line, MCF-7, delivery of PHENSS using the sCX[4]-dendrimer nanocomplexes, regardless of dendrimer generation, had little effect on PHENSS cytotoxicity. The results of this study may have application in the delivery of a variety of small molecule metal-based drugs for which chemical conjugation to a nanoparticle is undesired or not feasible. Copyright © 2017 Elsevier Inc. All rights reserved.

Synthesis and characterization of polyamidoamine dendrimer-coated multi-walled carbon nanotubes and their application in gene delivery systems

Science.gov (United States)

Pan, Bifeng; Cui, Daxiang; Xu, Ping; Ozkan, Cengiz; Feng, Gao; Ozkan, Mihri; Huang, Tuo; Chu, Bingfeng; Li, Qing; He, Rong; Hu, Guohan

2009-03-01

With the aim of improving the amount and delivery efficiency of genes taken by carbon nanotubes into human cancer cells, different generations of polyamidoamine dendrimer modified multi-walled carbon nanotubes (dMNTs) were fabricated, and characterized by high-resolution transmission electron microscopy, atomic force microscopy, x-ray photoelectron spectroscopy, Raman spectroscopy, Fourier transform infrared spectroscopy and thermogravimetric analysis, revealing the presence of dendrimer capped on the surface of carbon nanotubes. The dMNTs fully conjugated with FITC-labeled antisense c-myc oligonucleotides (asODN), those resultant asODN-dMNTs composites were incubated with human breast cancer cell line MCF-7 cells and MDA-MB-435 cells, and liver cancer cell line HepG2 cells, and confirmed to enter into tumor cells within 15 min by laser confocal microscopy. These composites inhibited the cell growth in time- and dose-dependent means, and down-regulated the expression of the c-myc gene and C-Myc protein. Compared with the composites of CNT-NH2-asODN and dendrimer-asODN, no. 5 generation of dendrimer-modified MNT-asODN composites exhibit maximal transfection efficiencies and inhibition effects on tumor cells. The intracellular gene transport and uptake via dMNTs should be generic for the mammalian cell lines. The dMNTs have potentials in applications such as gene or drug delivery for cancer therapy and molecular imaging.

Synthesis and characterization of polyamidoamine dendrimer-coated multi-walled carbon nanotubes and their application in gene delivery systems

Energy Technology Data Exchange (ETDEWEB)

Pan Bifeng; Cui Daxiang; Xu Ping; Feng Gao; Huang Tuo; Li Qing; He Rong [Department of Bio-Nano-Science and Engineering, National Key Laboratory of Nano/Micro Fabrication Technology, Key Laboratory for Thin Film and Microfabrication of Ministry of Education, Institute of Micro-Nano Science and Technology, Shanghai JiaoTong University, 800 Dongchuan Road, Shanghai 200240 (China); Ozkan, Cengiz [Mechanical Engineering Department, University of California Riverside, 900 University Avenue-Riverside, CA 92521 (United States); Ozkan, Mihri [Electrical Engineering Department, University of California Riverside, 900 University Avenue, Riverside, CA 92521 (United States); Chu, Bingfeng [Department of Stomatology, General Hospital of PLA, 28 Fuxing Road, Beijing100853 (China); Hu Guohan [Department of Neurosurgery of Changzheng Hospital, 415 Fengyang Road, Second Military Medical University, Shanghai 20003 (China)], E-mail: dxcui@sjtu.edu.cn, E-mail: huguohan6504@sina.com

2009-03-25

With the aim of improving the amount and delivery efficiency of genes taken by carbon nanotubes into human cancer cells, different generations of polyamidoamine dendrimer modified multi-walled carbon nanotubes (dMNTs) were fabricated, and characterized by high-resolution transmission electron microscopy, atomic force microscopy, x-ray photoelectron spectroscopy, Raman spectroscopy, Fourier transform infrared spectroscopy and thermogravimetric analysis, revealing the presence of dendrimer capped on the surface of carbon nanotubes. The dMNTs fully conjugated with FITC-labeled antisense c-myc oligonucleotides (asODN), those resultant asODN-dMNTs composites were incubated with human breast cancer cell line MCF-7 cells and MDA-MB-435 cells, and liver cancer cell line HepG2 cells, and confirmed to enter into tumor cells within 15 min by laser confocal microscopy. These composites inhibited the cell growth in time- and dose-dependent means, and down-regulated the expression of the c-myc gene and C-Myc protein. Compared with the composites of CNT-NH{sub 2}-asODN and dendrimer-asODN, no. 5 generation of dendrimer-modified MNT-asODN composites exhibit maximal transfection efficiencies and inhibition effects on tumor cells. The intracellular gene transport and uptake via dMNTs should be generic for the mammalian cell lines. The dMNTs have potentials in applications such as gene or drug delivery for cancer therapy and molecular imaging.

Synthesis and characterization of polyamidoamine dendrimer-coated multi-walled carbon nanotubes and their application in gene delivery systems

International Nuclear Information System (INIS)

Pan Bifeng; Cui Daxiang; Xu Ping; Feng Gao; Huang Tuo; Li Qing; He Rong; Ozkan, Cengiz; Ozkan, Mihri; Chu, Bingfeng; Hu Guohan

2009-01-01

With the aim of improving the amount and delivery efficiency of genes taken by carbon nanotubes into human cancer cells, different generations of polyamidoamine dendrimer modified multi-walled carbon nanotubes (dMNTs) were fabricated, and characterized by high-resolution transmission electron microscopy, atomic force microscopy, x-ray photoelectron spectroscopy, Raman spectroscopy, Fourier transform infrared spectroscopy and thermogravimetric analysis, revealing the presence of dendrimer capped on the surface of carbon nanotubes. The dMNTs fully conjugated with FITC-labeled antisense c-myc oligonucleotides (asODN), those resultant asODN-dMNTs composites were incubated with human breast cancer cell line MCF-7 cells and MDA-MB-435 cells, and liver cancer cell line HepG2 cells, and confirmed to enter into tumor cells within 15 min by laser confocal microscopy. These composites inhibited the cell growth in time- and dose-dependent means, and down-regulated the expression of the c-myc gene and C-Myc protein. Compared with the composites of CNT-NH 2 -asODN and dendrimer-asODN, no. 5 generation of dendrimer-modified MNT-asODN composites exhibit maximal transfection efficiencies and inhibition effects on tumor cells. The intracellular gene transport and uptake via dMNTs should be generic for the mammalian cell lines. The dMNTs have potentials in applications such as gene or drug delivery for cancer therapy and molecular imaging.

Interaction of poly(amidoamine) dendrimers with supported lipid bilayers and cells: hole formation and the relation to transport.

Science.gov (United States)

Hong, Seungpyo; Bielinska, Anna U; Mecke, Almut; Keszler, Balazs; Beals, James L; Shi, Xiangyang; Balogh, Lajos; Orr, Bradford G; Baker, James R; Banaszak Holl, Mark M

2004-01-01

We have investigated poly(amidoamine) (PAMAM) dendrimer interactions with supported 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid bilayers and KB and Rat2 cell membranes using atomic force microscopy (AFM), enzyme assays, flow cell cytometry, and fluorescence microscopy. Amine-terminated generation 7 (G7) PAMAM dendrimers (10-100 nM) were observed to form holes of 15-40 nm in diameter in aqueous, supported lipid bilayers. G5 amine-terminated dendrimers did not initiate hole formation but expanded holes at existing defects. Acetamide-terminated G5 PAMAM dendrimers did not cause hole formation in this concentration range. The interactions between PAMAM dendrimers and cell membranes were studied in vitro using KB and Rat 2 cell lines. Neither G5 amine- nor acetamide-terminated PAMAM dendrimers were cytotoxic up to a 500 nM concentration. However, the dose dependent release of the cytoplasmic proteins lactate dehydrogenase (LDH) and luciferase (Luc) indicated that the presence of the amine-terminated G5 PAMAM dendrimer decreased the integrity of the cell membrane. In contrast, the presence of acetamide-terminated G5 PAMAM dendrimer had little effect on membrane integrity up to a 500 nM concentration. The induction of permeability caused by the amine-terminated dendrimers was not permanent, and leaking of cytosolic enzymes returned to normal levels upon removal of the dendrimers. The mechanism of how PAMAM dendrimers altered cells was investigated using fluorescence microscopy, LDH and Luc assays, and flow cytometry. This study revealed that (1) a hole formation mechanism is consistent with the observations of dendrimer internalization, (2) cytosolic proteins can diffuse out of the cell via these holes, and (3) dye molecules can be detected diffusing into the cell or out of the cell through the same membrane holes. Diffusion of dendrimers through holes is sufficient to explain the uptake of G5 amine-terminated PAMAM dendrimers into cells and is consistent

Understanding AuNP interaction with low-generation PAMAM dendrimers: a CIELab and deconvolution study

International Nuclear Information System (INIS)

Jimenez-Ruiz, A.; Carnerero, J. M.; Castillo, P. M.; Prado-Gotor, R.

2017-01-01

Low-generation polyamidoamine (PAMAM) dendrimers are known to adsorb on the surface of gold nanoparticles (AuNPs) causing aggregation and color changes. In this paper, a thorough study of this affinity using absorption spectroscopy, colorimetric, and emission methods has been carried out. Results show that, for citrate-capped gold nanoparticles, interaction with the dendrimer is not only of an electrostatic character but instead occurs, at least in part, through the dendrimer’s uncharged internal amino groups. The possibilities of the CIELab chromaticity system parameters’ evolution have also been explored in order to quantify dendrimer interaction with the red-colored nanoparticles. By measuring and quantifying 17 nm citrate-capped AuNP color changes, which are strongly dependant on their aggregation state, binding free energies are obtained for the first time for these systems. Results are confirmed via an alternate fitting method which makes use of deconvolution parameters from absorbance spectra. Binding free energies obtained through the use of both means are in good agreement with each other.

Understanding AuNP interaction with low-generation PAMAM dendrimers: a CIELab and deconvolution study

Energy Technology Data Exchange (ETDEWEB)

Jimenez-Ruiz, A., E-mail: ailjimrui@alum.us.es; Carnerero, J. M.; Castillo, P. M.; Prado-Gotor, R., E-mail: pradogotor@us.es [University of Seville, The Department of Physical Chemistry (Spain)

2017-01-15

Low-generation polyamidoamine (PAMAM) dendrimers are known to adsorb on the surface of gold nanoparticles (AuNPs) causing aggregation and color changes. In this paper, a thorough study of this affinity using absorption spectroscopy, colorimetric, and emission methods has been carried out. Results show that, for citrate-capped gold nanoparticles, interaction with the dendrimer is not only of an electrostatic character but instead occurs, at least in part, through the dendrimer’s uncharged internal amino groups. The possibilities of the CIELab chromaticity system parameters’ evolution have also been explored in order to quantify dendrimer interaction with the red-colored nanoparticles. By measuring and quantifying 17 nm citrate-capped AuNP color changes, which are strongly dependant on their aggregation state, binding free energies are obtained for the first time for these systems. Results are confirmed via an alternate fitting method which makes use of deconvolution parameters from absorbance spectra. Binding free energies obtained through the use of both means are in good agreement with each other.

Intracellular Ca2+ release mediates cationic but not anionic poly(amidoamine) (PAMAM) dendrimer-induced tight junction modulation.

Science.gov (United States)

Avaritt, Brittany R; Swaan, Peter W

2014-09-01

Poly(amidoamine) (PAMAM) dendrimers show great promise for utilization as oral drug delivery vehicles. These polymers are capable of traversing epithelial barriers, and have been shown to translocate by both transcellular and paracellular routes. While many proof-of-concept studies have shown that PAMAM dendrimers improve intestinal transport, little information exists on the mechanisms of paracellular transport, specifically dendrimer-induced tight junction modulation. Using anionic G3.5 and cationic G4 PAMAM dendrimers with known absorption enhancers, we investigated tight junction modulation in Caco-2 monolayers by visualization and mannitol permeability and compared dendrimer-mediated tight junction modulation to that of established permeation enhancers. [(14)C]-Mannitol permeability in the presence and absence of phospholipase C-dependent signaling pathway inhibitors was also examined and indicated that this pathway may mediate dendrimer-induced changes in permeability. Differences between G3.5 and G4 in tight junction protein staining and permeability with inhibitors were evident, suggesting divergent mechanisms were responsible for tight junction modulation. These dissimilarities are further intimated by the intracellular calcium release caused by G4 but not G3.5. Based on our results, it is apparent that the underlying mechanisms of dendrimer permeability are complex, and the complexities are likely a result of the density and sign of the surface charges of PAMAM dendrimers. The results of this study will have implications on the future use of PAMAM dendrimers for oral drug delivery.

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…

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

Science.gov (United States)

Caminade, Anne-Marie; Majoral, Jean-Pierre

2018-03-09

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

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.

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).

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

In Vitro Evaluation of Third Generation PAMAM Dendrimer Conjugates

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Mohammad Najlah

2017-10-01

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

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

Directory of Open Access Journals (Sweden)

Anne-Marie Caminade

2018-03-01

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

Electronic transport study in PAMAM dendrimers

International Nuclear Information System (INIS)

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

2005-01-01

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

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...

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

International Nuclear Information System (INIS)

Khodadust, Rouhollah; Unsoy, Gozde; Yalcın, Serap; Gunduz, Gungor; Gunduz, Ufuk

2013-01-01

This study focuses on the synthesis and characterization of different generations (G 0 –G 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.

Proton-conductive materials formed by coumarin photocrosslinked ionic liquid crystal dendrimers

NARCIS (Netherlands)

Concellon, A.; Liang, T.; Schenning, A.P.H.J.; Luis Serrano, J.; Romero, P.; Marcos, M.

2018-01-01

In this work, we have successfully examined for the first time the use of ionic dendrimers as building blocks for the preparation of 1D and 2D proton conductive materials. For this purpose, a new family of liquid crystalline dendrimers has been synthesized by ionic self-assembly of poly(amidoamine)

Direct synthesis and morphological characterization of gold-dendrimer nanocomposites prepared using PAMAM succinamic acid dendrimers: preliminary study of the calcification potential.

Science.gov (United States)

Vasile, E; Serafim, A; Petre, D; Giol, D; Dubruel, P; Iovu, H; Stancu, I C

2014-01-01

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

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.

Thermodynamic Properties of a First-Generation Carbosilane Dendrimer with Terminal Phenylethyl Groups

Science.gov (United States)

Sologubov, S. S.; Markin, A. V.; Smirnova, N. N.; Novozhilova, N. A.; Tatarinova, E. A.; Muzafarov, A. M.

2018-02-01

The heat capacity of a first-generation carbosilane dendrimer with terminal phenylethyl groups as a function of temperature in the range from 6 to 520 K is studied for the first time via precision adiabatic vacuum calorimetry and differential scanning calorimetry. Physical transformations, such as low-temperature structural anomaly and glass transition are detected in the above-mentioned range of temperatures, and their standard thermodynamic characteristics are determined and analyzed. The standard thermodynamic functions of the studied dendrimer in the range of T → 0 to 520 K are calculated from the experimental data, as is the standard entropy in the devitrified state at T = 298.15 K. The standard thermodynamic characteristics of the carbosilane dendrimers studied in this work and earlier are compared.

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.

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

International Nuclear Information System (INIS)

López-Cabaña, Z.E.; Valdés, O.; Vergara, C.E.; Camarada, M.B.; Nachtigall, F.M.; González-Nilo, F.D.; Santos, Leonardo S.

2015-01-01

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

Cellular uptake of glucoheptoamidated poly(amidoamine) PAMAM G3 dendrimer with amide-conjugated biotin, a potential carrier of anticancer drugs.

Science.gov (United States)

Uram, Łukasz; Szuster, Magdalena; Filipowicz, Aleksandra; Zaręba, Magdalena; Wałajtys-Rode, Elżbieta; Wołowiec, Stanisław

2017-01-15

In search for soluble derivatives of PAMAM dendrimers as potential carriers for hydrophobic drugs, the conjugates of PAMAM G3 with biotin, further converted into glycodendrimer with d-glucoheptono-1,4-lactone, were prepared. Polyamidoamine dendrimer (PAMAM) of third generation, G3 was functionalized with four biotin equivalents covalently attached to terminal amine nitrogens via amide bond G3 4B . The remaining 28 amine groups were blocked by glucoheptoamide substituents (gh) to give G3 4B28gh or with one fluorescein equivalent (attached by reaction of G3 4B with fluorescein isothiocyanate, FITC) via thiourea bond as FITC followed by exhaustive glucoheptoamidation to get G3 4B27gh1F . As a control the G3 substituted totally with 32 glucoheptoamide residues, G3 gh and its fluorescein labeled analogue G3 31gh1F were synthesized. The glucoheptoamidation of PAMAM G0 dendrimer with glucoheptono-1,4-lactone was performed in order to fully characterize the 1 H NMR spectra of glucoheptoamidated PAMAM dendrimers and to control the derivatization of G3 with glucoheptono-1,4-lactone. Another two derivatives of G3, namely G3 4B28gh1F' and G3 32ghF' , with ester bonded fluorescein were also obtained. Biological properties of obtained dendrimer conjugates were estimated in vitro with human cell lines: normal fibroblast (BJ) and two cancer glioblastoma (U-118 MG) and squamous carcinoma (SCC-15), including cytotoxicity by reduction of XTT and neutral red (NR) assays. Cellular uptake of dendrimer conjugates was evaluated with confocal microscopy. Obtained results confirmed, that biotinylated bioconjugates have always lower cytotoxicity and 3-4 times higher cellular uptake than non-biotinylated dendrimer conjugates in all cell lines. Comparison of various cell lines revealed different dose-dependent cell responses and the lower cytotoxicity of examined dendrimer conjugates for normal fibroblasts and squamous carcinoma, as compared with much higher cytotoxic effects seen in

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

International Nuclear Information System (INIS)

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

2006-01-01

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

Gold nano particle decorated graphene core first generation PAMAM dendrimer for label free electrochemical DNA hybridization sensing.

Science.gov (United States)

Jayakumar, K; Rajesh, R; Dharuman, V; Venkatasan, R; Hahn, J H; Pandian, S Karutha

2012-01-15

A novel first generation (G1) poly(amidoamine) dendrimer (PAMAM) with graphene core (GG1PAMAM) was synthesized for the first time. Single layer of GG1PAMAM was immobilized covalently on mercaptopropionic acid (MPA) monolayer on Au transducer. This allows cost effective and easy deposition of single layer graphene on the Au transducer surface than the advanced vacuum techniques used in the literature. Au nano particles (17.5 nm) then decorated the GG1PAMAM and used for electrochemical DNA hybridization sensing. The sensor discriminates selectively and sensitively the complementary double stranded DNA (dsDNA, hybridized), non-complementary DNA (ssDNA, un-hybridized) and single nucleotide polymorphism (SNP) surfaces. Interactions of the MPA, GG1PAMAM and the Au nano particles were characterized by Ultra Violet (UV), Fourier Transform Infrared (FTIR), Raman spectroscopy (RS), Thermo gravimetric analysis (TGA), Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), Cyclic Voltmetric (CV), Impedance spectroscopy (IS) and Differntial Pulse Voltammetry (DPV) techniques. The sensor showed linear range 1×10(-6) to 1×10(-12) M with lowest detection limit 1 pM which is 1000 times lower than G1PAMAM without graphene core. Copyright © 2011 Elsevier B.V. All rights reserved.

Solubility improvement of an anthelmintic benzimidazole carbamate by association with dendrimers

International Nuclear Information System (INIS)

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

2011-01-01

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

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

Science.gov (United States)

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

2018-05-01

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

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

Science.gov (United States)

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

2016-09-12

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

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

Science.gov (United States)

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

2009-11-01

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

Solubility improvement of an anthelmintic benzimidazole carbamate by association with dendrimers

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L. Fernández

2011-12-01

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

Solubility improvement of an anthelmintic benzimidazole carbamate by association with dendrimers

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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)

Comparative toxicological assessment of PAMAM and thiophosphoryl dendrimers using embryonic zebrafish

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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

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

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

2015-01-01

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

A molecular dynamics study of the structure and inter-particle interactions of polyethylene glycol-conjugated PAMAM dendrimers

OpenAIRE

Lee, Hwankyu; Larson, Ronald G.

2009-01-01

We performed molecular dynamics (MD) simulations of one or two copies of polyethylene glycol of molecular weight 550 (PEG550) and 5000 (PEG5000) Daltons, conjugated to generation 3 (G3) to 5 (G5) polyamidoamine (PAMAM) dendrimers with explicit water using a coarse-grained model. We found the radii of gyration of these dendrimer-PEG molecules to be close to those measured in experiments by Hedden and Bauer (Macromolecules 2003, 36, 1829). Densely grafted PEG ligands (>50% of the dendrimer surf...

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

Energy Technology Data Exchange (ETDEWEB)

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

2007-02-26

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

DNA assisted self-assembly of PAMAM dendrimers.

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

2014-10-09

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

Molecular dynamic analysis of the structure of dendrimers

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

2004-01-01

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

Molecular dynamic analysis of the structure of dendrimers

International Nuclear Information System (INIS)

Canetta, E.; Maino, G.

2004-01-01

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

Fluorescent quantum dot hydrophilization with PAMAM dendrimer

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

2016-05-01

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

Fluorescent quantum dot hydrophilization with PAMAM dendrimer

Energy Technology Data Exchange (ETDEWEB)

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

2016-05-15

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

Fluorescent properties of novel dendrimer dyes based on thiazole orange

International Nuclear Information System (INIS)

Fei Xuening; Gu Yingchun; Lan Yunquan; Shi Bin

2011-01-01

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

Layer-by-Layer-Assembled AuNPs-Decorated First-Generation Poly(amidoamine) Dendrimer with Reduced Graphene Oxide Core as Highly Sensitive Biosensing Platform with Controllable 3D Nanoarchitecture for Rapid Voltammetric Analysis of Ultratrace DNA Hybridization.

Science.gov (United States)

Jayakumar, Kumarasamy; Camarada, María Belén; Dharuman, Venkataraman; Rajesh, Rajendiran; Venkatesan, Rengarajan; Ju, Huangxian; Maniraj, Mahalingam; Rai, Abhishek; Barman, Sudipta Roy; Wen, Yangping

2018-06-12

The structure and electrochemical properties of layer-by-layer-assembled gold nanoparticles (AuNPs)-decorated first-generation (G1) poly(amidoamine) dendrimer (PD) with reduced graphene oxide (rGO) core as a highly sensitive and label-free biosensing platform with a controllable three-dimensional (3D) nanoarchitecture for the rapid voltammetric analysis of DNA hybridization at ultratrace levels were characterized. Mercaptopropinoic acid (MPA) was self-assembled onto Au substrate, then GG1PD formed by the covalent functionalization between the amino terminals of G1PD and carboxyl terminals of rGO was covalently linked onto MPA, and finally AuNPs were decorated onto GG1PD by strong physicochemical interaction between AuNPs and -OH of rGO in GG1PD, which was characterized through different techniques and confirmed by computational calculation. This 3D controllable thin-film electrode was optimized and evaluated using [Fe(CN) 6 ] 3-/4- as the redox probe and employed to covalently immobilize thiol-functionalized single-stranded DNA as biorecognition element to form the DNA nanobiosensor, which achieved fast, ultrasensitive, and high-selective differential pulse voltammetric analysis of DNA hybridization in a linear range from 1 × 10 -6 to 1 × 10 -13 g m -1 with a low detection limit of 9.07 × 10 -14 g m -1 . This work will open a new pathway for the controllable 3D nanoarchitecture of the layer-by-layer-assembled metal nanoparticles-functionalized lower-generation PD with two-dimensional layered nanomaterials as cores that can be employed as ultrasensitive and label-free nanobiodevices for the fast diagnosis of specific genome diseases in the field of biomedicine.

Poly(amido amine) dendrimers in oral delivery.

Science.gov (United States)

Yellepeddi, Venkata K; Ghandehari, Hamidreza

2016-01-01

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

Effect of generation on the electronic properties of light-emitting dendrimers

Science.gov (United States)

Burn, Paul L.; Halim, Mounir; Pillow, Jonathan N. G.; Samuel, Ifor D. W.

1999-12-01

We have compared the optical and electronic properties of a series of porphyrin centered dendrimers containing stilbene dendrons. The first and second generation dendrimers could be spin-coated from solution to form good quality thin films. Incorporation into single layer light-emitting diodes gave red-light emission with maximum external quantum efficiencies of 0.02% and 0.04% for the first and second generation dendrimers respectively. We have determined by photoluminescence studies that energy can be transferred efficiently from the stilbene dendrons to the porphyrin core and that PL emission is from the core. Cyclic voltammetry studies on the dendrimers show that the reductions are porphyrin centered with the dendrons only affecting the rate of heterogeneous electron transfer between the electrode and the dendrimers. This suggests that charge mobility within a dendrimer film in an LED will be affected by the porphyrin edge to porphyrin edge distance. We have studied the hydrodynamic radii of the dendrimers by gel permeation chromatography and found as expected that the average porphyrin edge to dendron edge distance increases with generation. This is consistent with the slowing of heterogeneous electron transfer observed in the cyclic voltammetry on increasing the generation number and suggests that the dendrons are interleaved in the solid state to facilitate charge transport.

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

Folic acid-decorated polyamidoamine dendrimer exhibits high tumor uptake and sustained highly localized retention in solid tumors: Its utility for local siRNA delivery.

Science.gov (United States)

Xu, Leyuan; Yeudall, W Andrew; Yang, Hu

2017-07-15

The utility of folic acid (FA)-decorated polyamidoamine dendrimer G4 (G4-FA) as a vector was investigated for local delivery of siRNA. In a xenograft HN12 (or HN12-YFP) tumor mouse model of head and neck squamous cell carcinomas (HNSCC), intratumorally (i.t.) injected G4-FA exhibited high tumor uptake and sustained highly localized retention in the tumors according to near infrared (NIR) imaging assessment. siRNA against vascular endothelial growth factor A (siVEGFA) was chosen as a therapeutic modality. Compared to the nontherapeutic treatment groups (PBS solution or dendrimer complexed with nontherapeutic siRNA against green fluorescent protein (siGFP)), G4-FA/siVEGFA showed tumor inhibition effects in single-dose and two-dose regimen studies. In particular, two doses of G4-FA/siVEGFA i.t. administered eight days apart resulted in a more profound inhibition of tumor growth, accompanied with significant reduction in angiogenesis, as judged by CD31 staining and microvessel counts. Tumor size reduction in the two-dose regimen study was ascertained semi-quantitatively by live fluorescence imaging of YFP tumors and independently supported antitumor effects of G4-FA/siVEGFA. Taken together, G4-FA shows high tumor uptake and sustained retention properties, making it a suitable platform for local delivery of siRNAs to treat cancers that are readily accessible such as HNSCC. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and is difficult to transfect for gene therapy. We developed folate receptor (FR)-targeted polyamidoamine (PAMAM) dendrimer for enhanced delivery of genes to HNSCC and gained in-depth understanding of how gene delivery and transfection in head and neck squamous cancer cells can be enhanced via FR-targeted PAMAM dendrimers. The results we report here are encouraging and present latest advances in using dendrimers for cancer therapies, in particular for HNSCC. Our work has demonstrated that localized delivery of FR

A review on comparative study of PPI and PAMAM dendrimers

International Nuclear Information System (INIS)

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

2016-01-01

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

A review on comparative study of PPI and PAMAM dendrimers

Energy Technology Data Exchange (ETDEWEB)

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

2016-06-15

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

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

Science.gov (United States)

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

2014-06-01

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

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

Investigation of Dendrimer-Membrane Interactions

Science.gov (United States)

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

2003-03-01

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

Molecular dynamics study of charged dendrimers in salt-free solution : effect of counterions

NARCIS (Netherlands)

Gurtovenko, A.A.; Lyulin, S.V.; Karttunen, M.E.J.; Vattulainen, I.

2006-01-01

Polyamidoamine dendrimers, being protonated under physiological conditions, represent a promising class of nonviral, nanosized vectors for drug and gene delivery. We performed extensive molecular dynamics simulations of a generic model dendrimer in a salt-free solution with dendrimer’s terminal

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

Science.gov (United States)

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

2016-01-01

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

PEGylated Polyamidoamine dendrimer conjugated with tumor homing peptide as a potential targeted delivery system for glioma.

Science.gov (United States)

Jiang, Yan; Lv, Lingyan; Shi, Huihui; Hua, Yabing; Lv, Wei; Wang, Xiuzhen; Xin, Hongliang; Xu, Qunwei

2016-11-01

Glioblastoma multiforme (GBM) is the most common and aggressive primary central nervous system (CNS) tumor with a short survival time. The failure of chemotherapy is ascribed to the low transport of chemotherapeutics across the Blood Brain Tumor Barrier (BBTB) and poor penetration into tumor tissue. In order to overcome the two barriers, small nanoparticles with active targeted capability are urgently needed for GBM drug delivery. In this study, we proposed PEGylated Polyamidoamine (PAMAM) dendrimer nanoparticles conjugated with glioma homing peptides (Pep-1) as potential glioma targeting delivery system (Pep-PEG-PAMAM), where PEGylated PAMAM dendrimer nanoparticle was utilized as carrier due to its small size and perfect penetration into tumor and Pep-1 was used to overcome BBTB via interleukin 13 receptor α2 (IL-13Rα2) mediated endocytosis. The preliminary availability and safety of Pep-PEG-PAMAM as a nanocarrier for glioma was evaluated. In vitro results indicated that a significantly higher amount of Pep-PEG-PAMAM was endocytosed by U87 MG cells. In vivo fluorescence imaging of U87MG tumor-bearing mice confirmed that the fluorescence intensity at glioma site of targeted group was 2.02 folds higher than that of untargeted group (**p<0.01), and glioma distribution experiment further revealed that Pep-PEG-PAMAM exhibited a significantly enhanced accumulation and improved penetration at tumor site. In conclusion, Pep-1 modified PAMAM was a promising nanocarrier for targeted delivery of brain glioma. Copyright © 2016 Elsevier B.V. All rights reserved.

Photoinduced Electron Transfer of PAMAM Dendrimer-Zinc(II) Porphyrin Associates at Polarized Liquid|Liquid Interfaces.

Science.gov (United States)

Nagatani, Hirohisa; Sakae, Hiroki; Torikai, Taishi; Sagara, Takamasa; Imura, Hisanori

2015-06-09

The heterogeneous photoinduced electron-transfer reaction of the ion associates between NH2-terminated polyamidoamine (PAMAM) dendrimers and 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato zinc(II) (ZnTPPS(4-)) was studied at the polarized water|1,2-dichloroethane (DCE) interface. The positive photocurrent arising from the photoreduction of ZnTPPS(4-) by a lipophilic quencher, decamethylferrocene, in the interfacial region was significantly enhanced by the ion association with the PAMAM dendrimers. The photocurrent response of the dendrimer-ZnTPPS(4-) associates was dependent on the pH condition and on the generation of dendrimer. A few cationic additives such as polyallylamine and n-octyltrimethyammonium were also examined as alternatives to the PAMAM dendrimer, but the magnitude of the photocurrent enhancement was rather small. The high photoreactivity of the dendrimer-ZnTPPS(4-) associates was interpreted mainly as a result of the high interfacial concentration of photoreactive porphyrin units associated stably with the dendrimer which was preferably adsorbed at the polarized water|DCE interface. The photochemical data observed in the second and fourth generation PAMAM dendrimer systems demonstrated that the higher generation dendrimer which can incorporate a porphyrin molecule more completely in the interior is less efficient for the photocurrent enhancement at the interface. These results indicated that the photoreactivity of ionic reactant at a polarized liquid|liquid interface can readily be modified via ion association with the charged dendrimer.

Separation of poly(amidoamine) (PAMAM) dendrimer generations by dynamic coating capillary electrophoresis

Czech Academy of Sciences Publication Activity Database

Sedláková, Pavla; Svobodová, Jana; Mikšík, Ivan; Tomás, H.

2006-01-01

Roč. 841, č. 1-2 (2006), s. 135-139 ISSN 1570-0232 R&D Projects: GA ČR(CZ) GA203/03/0716; GA ČR(CZ) GA203/05/2539; GA MŠk(CZ) 1M0510 Grant - others:GA-(PT) GRICES Institutional research plan: CEZ:AV0Z50110509 Keywords : PAMAM dendrimer s * dynamic coating Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 2.647, year: 2006

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

International Nuclear Information System (INIS)

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

2017-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2017-03-01

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

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.

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

International Nuclear Information System (INIS)

Baccarin, Marina; Janegitz, Bruno C.; Berté, Rodrigo; Vicentini, Fernando Campanhã; Banks, Craig E.; Fatibello-Filho, Orlando

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"3"+ present in the heme group in Hb, as revealed by cyclic voltammetry in the presence of O_2. An apparent heterogeneous electron transfer rate of 4.1 s"−"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"−"6 to 9.1 × 10"−"5 mol L"−"1 with a detection limit of 4.9 × 10"−"6 mol L"−"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_2O_2 is determined by amperometry using the proposed third generation biosensor. • The direct electron transfer was obtained from Hb using Hb–AgNPs–PAMAM.

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.

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

Science.gov (United States)

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

2017-03-01

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

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

Science.gov (United States)

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

2017-12-01

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

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.

Determination of spectral markers of cytotoxicity and genotoxicity using in vitro Raman microspectroscopy: cellular responses to polyamidoamine dendrimer exposure.

Science.gov (United States)

Efeoglu, Esen; Casey, Alan; Byrne, Hugh J

2017-10-09

Although consumer exposure to nanomaterials is ever increasing, with potential increased applications in areas such as drug and/or gene delivery, contrast agents and diagnosis, the determination of the cyto- and geno-toxic effects of nanomaterials on human health and the environment still remains challenging. Although many techniques have been established and adapted to determine the cytotoxicity and genotoxicity of nano-sized materials, these techniques remain limited by the number of assays required, total cost, and use of labels and they struggle to explain the underlying interaction mechanisms. In this study, Raman microspectroscopy is employed as an in vitro label-free, high content screening technique to observe toxicological changes within the cell in a multi-parametric fashion. The evolution of spectral markers as a function of time and applied dose has been used to elucidate the mechanism of action of polyamidoamine (PAMAM) dendrimers associated with cytotoxicity and their impact on nuclear biochemistry. PAMAM dendrimers are chosen as a model nanomaterial due to their widely studied cytotoxic and genotoxic properties and commercial availability. Point spectra were acquired from the cytoplasm to monitor the cascade of toxic events occurring in the cytoplasm upon nanoparticle exposure, whereas the spectra acquired from the nucleus and the nucleolus were used to explore PAMAM-nuclear material interaction as well as genotoxic responses.

Paramagnetic NMR investigation of dendrimer-based host-guest interactions.

Directory of Open Access Journals (Sweden)

Fei Wang

Full Text Available In this study, the host-guest behavior of poly(amidoamine (PAMAM dendrimers bearing amine, hydroxyl, or carboxylate surface functionalities were investigated by paramagnetic NMR studies. 2,2,6,6-Tetramethylpiperidinyloxy (TEMPO derivatives were used as paramagnetic guest molecules. The results showed that TEMPO-COOH significantly broaden the ¹H NMR peaks of amine- and hydroxyl-terminated PAMAM dendrimers. In comparison, no paramagnetic relaxation enhancement (PRE was observed between TEMPO-NH₂, TEMPO-OH and the three types of PAMAM dendrimers. The PRE phenomenon observed is correlated with the encapsulation of TEMPO-COOH within dendrimer pockets. Protonation of the tertiary amine groups within PAMAM dendrimers plays an important role during this process. Interestingly, the absence of TEMPO-COOH encapsulation within carboxylate-terminated PAMAM dendrimer is observed due to the repulsion of TEMPO-COO- anion and anionic dendrimer surface. The combination of paramagnetic probes and ¹H NMR linewidth analysis can be used as a powerful tool in the analysis of dendrimer-based host-guest systems.

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

Science.gov (United States)

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

2015-08-01

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

The structure of carbosilane dendrimers of higher generations

International Nuclear Information System (INIS)

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

2008-01-01

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

Delivery of paclitaxel across cellular barriers using a dendrimer-based nanocarrier.

Science.gov (United States)

Teow, Huey Minn; Zhou, Zhengyuan; Najlah, Mohammad; Yusof, Siti R; Abbott, N Joan; D'Emanuele, Antony

2013-01-30

The aim of this study was to investigate the ability of a third-generation (G3) polyamidoamine (PAMAM) dendrimer-based carrier to enhance the permeability of paclitaxel (pac) and to overcome cellular barriers. G3 dendrimers were surface modified with lauryl chains (L) and conjugated with paclitaxel (pac) via a glutaric anhydride (glu) linker, followed by labeling with FITC. Biological evaluation of the dendrimer and conjugates was conducted using the human colon adenocarcinoma cell line (Caco-2) and primary cultured porcine brain endothelial cells (PBECs). LDH assay was used to evaluate the cytotoxicity of the dendrimer and conjugates. Cytotoxicity studies showed that the conjugation of lauryl chains and paclitaxel on G3 dendrimer significantly (pdendrimer-drug conjugates demonstrated an increase in the apparent permeability coefficient (P(app)) in both apical to basolateral A→B and basolateral to apical B→A directions across both cell monolayers compared to unmodified G3 and free drug. The B→A P(app) of paclitaxel was significantly (ptransporter system in both cell models. L6-G3-glu-pac conjugate had approximately 12-fold greater permeability across both cell monolayers than that of paclitaxel alone. Copyright © 2012 Elsevier B.V. All rights reserved.

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

OpenAIRE

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

2007-01-01

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

Molecular dynamics study of the structure and interparticle interactions of polyethylene glycol-conjugated PAMAM dendrimers.

Science.gov (United States)

Lee, Hwankyu; Larson, Ronald G

2009-10-08

We performed molecular dynamics (MD) simulations of one or two copies of polyethylene glycol of molecular weight 550 (PEG550) and 5000 (PEG5000) daltons, conjugated to generation 3 (G3) to 5 (G5) polyamidoamine (PAMAM) dendrimers with explicit water using a coarse-grained model. We found the radii of gyration of these dendrimer-PEG molecules to be close to those measured in experiments by Hedden and Bauer (Hedden , R. C. ; Bauer , B. J. Macromolecules 2003 , 36 , 1829.). Densely grafted PEG ligands (>50% of the dendrimer surface) extend like brushes, with layer thickness in agreement with theory for starlike polymers. Two dendrimer-PEG complexes in the box drift away from each other, indicating that no aggregation is induced by either short or long PEG chains, conflicting with a recent view that the cytotoxicity of some PEGylated particles might be due to particle aggregation for long PEG lengths.

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

Science.gov (United States)

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

2015-04-07

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

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

Science.gov (United States)

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

2014-07-01

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

Small Angle Neutron Scattering Studies of the Counterion Effects on the Molecular Conformation and Structure of Charged G4 PAMAM Dendrimers in Aqueous Solutions

International Nuclear Information System (INIS)

Chen, Wei-Ren

2007-01-01

The structural properties of generation 4 (G4) poly(amidoamine) starburst dendrimers (PAMAM) with an ethylenediamine ne (EDA) central core in D O 2 solutions have been studied by small angle neutron scattering. Upon the addition of DCl , SANS patterns show a pronounced inter-particle 2 correlation peaks due to the strong repulsion introduced by the protonation of the amino groups of the dendrimers. By solving the Ornstein-Zernike integral equation (OZ) with hypernetted chain closure (HNC), the dendrimer-dendrimer er structure factor S(Q) is determined and used to fit the experimental data. Quantitative information such as the effective charge per dendrimer and its conformational change at different conditions can be obtained. The results obtained show clear evidence that significant counterion association occurs, strongly mediating the inter-dendrimer interaction. The influence of interplay between counterions and molecular protonation of dendrimers has strong effect on the dendrimer conformation and effective interaction.

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

International Nuclear Information System (INIS)

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

2009-01-01

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

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

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mitra Gholami

2016-06-01

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

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

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

2018-04-01

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

The Debye light scattering equation’s scaling relation reveals the purity of synthetic dendrimers

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Tseng, Hui-Yu; Chen, Hsiao-Ping [National Chung Cheng University, Department of Chemistry and Biochemistry (China); Tang, Yi-Hsuan [Kaohsiung Medical University, Department of Medicinal and Applied Chemistry (China); Chen, Hui-Ting [Kaohsiung Medical University, Department of Fragrance and Cosmetic Science (China); Kao, Chai-Lin, E-mail: clkao@kmu.edu.tw [Kaohsiung Medical University, Department of Medicinal and Applied Chemistry (China); Wang, Shau-Chun, E-mail: chescw@ccu.edu.tw [National Chung Cheng University, Department of Chemistry and Biochemistry (China)

2016-03-15

Spherical dendrimer structures cannot be structurally modeled using conventional polymer models of random coil or rod-like configurations during the calibration of the static light scattering (LS) detectors used to determine the molecular weight (M.W.) of a dendrimer or directly assess the purity of a synthetic compound. In this paper, we used the Debye equation-based scaling relation, which predicts that the static LS intensity per unit concentration is linearly proportional to the M.W. of a synthetic dendrimer in a dilute solution, as a tool to examine the purity of high-generational compounds and to monitor the progress of dendrimer preparations. Without using expensive equipment, such as nuclear magnetic resonance or mass spectrometry, this method only required an affordable flow injection set-up with an LS detector. Solutions of the purified dendrimers, including the poly(amidoamine) (PAMAM) dendrimer and its fourth to seventh generation pyridine derivatives with size range of 5–9 nm, were used to establish the scaling relation with high linearity. The use of artificially impure mixtures of six or seven generations revealed significant deviations from linearity. The raw synthesized products of the pyridine-modified PAMAM dendrimer, which included incompletely reacted dendrimers, were also examined to gauge the reaction progress. As a reaction toward a particular generational derivative of the PAMAM dendrimers proceeded over time, deviations from the linear scaling relation decreased. The difference between the polydispersity index of the incompletely converted products and that of the pure compounds was only about 0.01. The use of the Debye equation-based scaling relation, therefore, is much more useful than the polydispersity index for monitoring conversion processes toward an indicated functionality number in a given preparation.Graphical abstract.

The Debye light scattering equation’s scaling relation reveals the purity of synthetic dendrimers

International Nuclear Information System (INIS)

Tseng, Hui-Yu; Chen, Hsiao-Ping; Tang, Yi-Hsuan; Chen, Hui-Ting; Kao, Chai-Lin; Wang, Shau-Chun

2016-01-01

Spherical dendrimer structures cannot be structurally modeled using conventional polymer models of random coil or rod-like configurations during the calibration of the static light scattering (LS) detectors used to determine the molecular weight (M.W.) of a dendrimer or directly assess the purity of a synthetic compound. In this paper, we used the Debye equation-based scaling relation, which predicts that the static LS intensity per unit concentration is linearly proportional to the M.W. of a synthetic dendrimer in a dilute solution, as a tool to examine the purity of high-generational compounds and to monitor the progress of dendrimer preparations. Without using expensive equipment, such as nuclear magnetic resonance or mass spectrometry, this method only required an affordable flow injection set-up with an LS detector. Solutions of the purified dendrimers, including the poly(amidoamine) (PAMAM) dendrimer and its fourth to seventh generation pyridine derivatives with size range of 5–9 nm, were used to establish the scaling relation with high linearity. The use of artificially impure mixtures of six or seven generations revealed significant deviations from linearity. The raw synthesized products of the pyridine-modified PAMAM dendrimer, which included incompletely reacted dendrimers, were also examined to gauge the reaction progress. As a reaction toward a particular generational derivative of the PAMAM dendrimers proceeded over time, deviations from the linear scaling relation decreased. The difference between the polydispersity index of the incompletely converted products and that of the pure compounds was only about 0.01. The use of the Debye equation-based scaling relation, therefore, is much more useful than the polydispersity index for monitoring conversion processes toward an indicated functionality number in a given preparation.Graphical abstract

Carbon nanotube-polyamidoamine dendrimer hybrid-modified electrodes for highly sensitive electrochemical detection of microRNA24.

Science.gov (United States)

Li, Fengye; Peng, Jing; Zheng, Qiong; Guo, Xiang; Tang, Hao; Yao, Shouzhuo

2015-01-01

A simple and ultrasensitive microRNA (miRNA) electrochemical biosensor employing multiwalled carbon nanotube (MWCNT)-polyamidoamine (PAMAM) dendrimer and methylene blue (MB) redox indicator is reported in this work. The assay utilizes a glass carbon (GC) electrode modified with MWCNT-PAMAM, on which the oligonucleotide capture probes are immobilized. The electrochemical detection of miRNAs is completed by measuring the reduction signal change of MB before and after the probe hybridization with target miRNA (miRNA24 is used as a model case). The MWCNT-PAMAM/GC electrode shows greatly enhanced signal to MB reduction in contrast to bare GC electrode. The functionalization of MWCNT with PAMAM maintains the electrochemical property of MWCNT to MB reduction but minimizes the undesired adsorption of MB on the MWCNT surface. The effect of experimental variables on the miRNA detection is investigated and optimized. A detection limit of 0.5 fM and a linear peak current density-concentration relationship up to 100 nM are obtained following 60 min hybridization. The proposed assay is successfully used to detect miRNA24 in total RNA sample extracted from HeLa cells.

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

International Nuclear Information System (INIS)

Nowacka, Olga; Milowska, Katarzyna; Bryszewska, Maria

2015-01-01

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

Formation of Silver and Gold Dendrimer Nanocomposites

International Nuclear Information System (INIS)

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

1999-01-01

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

Reactive oxygen species (ROS) induced cytokine production and cytotoxicity of PAMAM dendrimers in J774A.1 cells

International Nuclear Information System (INIS)

Naha, Pratap C.; Davoren, Maria; Lyng, Fiona M.; Byrne, Hugh J.

2010-01-01

The immunotoxicity of three generations of polyamidoamine (PAMAM) dendrimers (G-4, G-5 and G-6) was evaluated in mouse macrophage cells in vitro. Using the Alamar blue and MTT assays, a generation dependent cytotoxicity of the PAMAM dendrimers was found whereby G-6 > G-5 > G-4. The toxic response of the PAMAM dendrimers correlated well with the number of surface primary amino groups, with increasing number resulting in an increase in toxic response. An assessment of intracellular ROS generation by the PAMAM dendrimers was performed by measuring the increased fluorescence as a result of intracellular oxidation of Carboxy H 2 DCFDA to DCF both quantitatively using plate reader and qualitatively by confocal laser scanning microscopy. The inflammatory mediators macrophage inflammatory protein-2 (MIP-2), tumour necrosis factor-α (TNF-α) and interleukin-6, (IL-6) were measured by the enzyme linked immunosorbant assay (ELISA) following exposure of mouse macrophage cells to PAMAM dendrimers. A generation dependent ROS and cytokine production was found, which correlated well with the cytotoxicological response and therefore number of surface amino groups. A clear time sequence of increased ROS generation (maximum at ∼ 4 h), TNF-α and IL-6 secretion (maximum at ∼ 24 h), MIP-2 levels and cell death (∼ 72 h) was observed. The intracellular ROS generation and cytokine production induced cytotoxicity point towards the mechanistic pathway of cell death upon exposure to PAMAM dendrimers.

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

Science.gov (United States)

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

2012-03-15

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

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.

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

International Nuclear Information System (INIS)

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

2008-01-01

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

Reactive Landing of Dendrimer Ions onto Activated Self-assembled Monolayer Surfaces

Energy Technology Data Exchange (ETDEWEB)

Hu, Qichi; Laskin, Julia

2014-02-06

The reactivity of gaseous, amine-terminated polyamidoamine (PAMAM) dendrimer ions with activated self-assembled monolayer (SAM) surfaces terminated with N-hydroxysuccinimidyl ester groups (NHS-SAM) is examined using mass-selected ion deposition combined with in situ infrared reflection absorption spectroscopy (IRRAS). The reaction extent is determined from depletion of the infrared band at 1753 cm-1, corresponding to the stretching vibration of the NHS carbonyl groups following ion deposition. For reaction yields below 10%, NHS band depletion follows a linear dependence on the ion dose. By comparing the kinetics plots obtained for 1,12-dodecanediamine and different generations of dendrimer ions (G0–G3) containing 4, 8, 16, and 32 terminal amino group, we demonstrate that the relative reaction efficiency increases linearly with the number of NH2 groups in the molecule. This finding is rationalized assuming the formation of multiple amide bonds upon collision of higher-generation dendrimers with NHS-SAM. Furthermore, by comparing the NHS band depletion following deposition of [M+4H]4+ ions of the G2 dendrimer at 30, 80, and 120 eV, we demonstrate that the ion’s kinetic energy has no measurable effect on reaction efficiency. Similarly, the ion’s charge state only has a minor effect on the reactive landing efficiency of dendrimer ions. Our results indicate that reactive landing is an efficient approach for highly selective covalent immobilization of complex multifunctional molecules onto organic surfaces terminated with labile functional groups.

Effect of Cross-Linking on the Mechanical and Thermal Properties of Poly(amidoamine) Dendrimer/Poly(vinyl alcohol) Hybrid Membranes for CO2 Separation.

Science.gov (United States)

Duan, Shuhong; Kai, Teruhiko; Saito, Takashi; Yamazaki, Kota; Ikeda, Kenichi

2014-04-08

Poly(amidoamine) (PAMAM) dendrimers were incorporated into cross-linked poly(vinyl alcohol) (PVA) matrix to improve carbon dioxide (CO2) separation performance at elevated pressures. In our previous studies, PAMAM/PVA hybrid membranes showed high CO2 separation properties from CO2/H2 mixed gases. In this study, three types of organic Ti metal compounds were selected as PVA cross-linkers that were used to prepare PAMAM/cross-linked PVA hybrid membranes. Characterization of the PAMAM/cross-linked PVA hybrid membranes was conducted using nanoindentation and thermogravimetric analyses. The effects of the cross-linker and CO2 partial pressure in the feed gas on CO2 separation performance were discussed. H2O and CO2 sorption of the PAMAM/PVA hybrid membranes were investigated to explain the obtained CO2 separation efficiencies.

Nature of the effective interaction between dendrimers

International Nuclear Information System (INIS)

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

2014-01-01

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

Nature of the effective interaction between dendrimers

Energy Technology Data Exchange (ETDEWEB)

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

2014-10-14

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

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

Poly(amido)amine (PAMAM) dendrimer-cisplatin complexes for chemotherapy of cisplatin-resistant ovarian cancer cells

Science.gov (United States)

Yellepeddi, Venkata Kashyap; Vangara, Kiran Kumar; Palakurthi, Srinath

2013-09-01

Dendrimer-cisplatin complexes were prepared using PAMAM dendrimers with terminal -NH2 and -COOH groups as well as biotin-conjugated dendrimers. Preformulation parameters of dendrimer-cisplatin complexes were studied using differential scanning calorimetry (DSC) and inductively coupled plasma-mass spectrometry (ICP-MS). Cytotoxicity and mechanism of cytotoxicity of dendrimer-cisplatin complexes was investigated in OVCAR-3, SKOV, A2780 and cisplatin-resistant CP70 human ovarian cancer cell lines. The loading of cisplatin in dendrimers was 11 % (w/w). PAMAM G4 dendrimers with amine surface groups (biotinylated and native) have shown 2.5- to 3.0-fold reduction in IC50 values in ovarian cancer cells when compared with carboxylate surface dendrimers ( p cisplatin complexes resulted in a 7.0-fold increase ( p cisplatin chemotherapy of ovarian cancer.

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

Science.gov (United States)

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

2011-03-17

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

Effect of Cross-Linking on the Mechanical and Thermal Properties of Poly(amidoamine Dendrimer/Poly(vinyl alcohol Hybrid Membranes for CO2 Separation

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Shuhong Duan

2014-04-01

Full Text Available Poly(amidoamine (PAMAM dendrimers were incorporated into cross-linked poly(vinyl alcohol (PVA matrix to improve carbon dioxide (CO2 separation performance at elevated pressures. In our previous studies, PAMAM/PVA hybrid membranes showed high CO2 separation properties from CO2/H2 mixed gases. In this study, three types of organic Ti metal compounds were selected as PVA cross-linkers that were used to prepare PAMAM/cross-linked PVA hybrid membranes. Characterization of the PAMAM/cross-linked PVA hybrid membranes was conducted using nanoindentation and thermogravimetric analyses. The effects of the cross-linker and CO2 partial pressure in the feed gas on CO2 separation performance were discussed. H2O and CO2 sorption of the PAMAM/PVA hybrid membranes were investigated to explain the obtained CO2 separation efficiencies.

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.

Fetal uptake of intra-amniotically delivered dendrimers in a mouse model of intrauterine inflammation and preterm birth.

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Burd, Irina; Zhang, Fan; Dada, Tahani; Mishra, Manoj K; Borbiev, Talaibek; Lesniak, Wojciech G; Baghlaf, Haitham; Kannan, Sujatha; Kannan, Rangaramanujam M

2014-08-01

Intrauterine inflammation is associated with preterm birth and can lead to fetal neuroinflammation and neurobehavioral disorders in newborns. Dendrimers can intrinsically target and deliver drugs for the treatment of neuroinflammation. We explore whether hydroxyl polyamidoamine (PAMAM) dendrimer (G4-OH)-based nanomedicines can be delivered to the fetus by intra-amniotic administration, in a mouse model of intrauterine inflammation. The time-dependent accumulation of G4-OH-fluorophore conjugate was quantified by fluorescence. These studies suggest that, after intra-amniotic administration, there is significant accumulation of dendrimer in the fetus gut and brain. In addition, there is some fetal-maternal transport of the dendrimer. Confocal microscopy confirmed the presence of G4-OH in the fetal brain, with a large accumulation in the brain blood vessels and the brain parenchyma, and some microglial uptake. We believe that intra-amniotic administration of G4-OH-drug nanomedicines may enable the treatment of diseases related to intrauterine inflammation and fetal neuroinflammation. Using a mouse model of intrauterin inflammation leading to neuroinflammation in the fetus, these investigators demonstrate that intra-amniotic delivery of hydroxyl polyamidoamine (PAMAM) dendrimer (G4-OH)-based nanomedicines may provide an effective method in preventing this complication. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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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.

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

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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

Mechanism of PAMAM Dendrimers Internalization in Hippocampal Neurons.

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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.

Prevention of Synaptic Alterations and Neurotoxic Effects of PAMAM Dendrimers by Surface Functionalization

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Felipe Vidal

2017-12-01

Full Text Available One of the most studied nanocarriers for drug delivery are polyamidoamine (PAMAM dendrimers. However, the alterations produced by PAMAM dendrimers in neuronal function have not been thoroughly investigated, and important aspects such as effects on synaptic transmission remain unexplored. We focused on the neuronal activity disruption induced by dendrimers and the possibility to prevent these effects by surface chemical modifications. Therefore, we studied the effects of fourth generation PAMAM with unmodified positively charged surface (G4 in hippocampal neurons, and compared the results with dendrimers functionalized in 25% of their surface groups with folate (PFO25 and polyethylene glycol (PPEG25. G4 dendrimers significantly reduced cell viability at 1 µM, which was attenuated by both chemical modifications, PPEG25 being the less cytotoxic. Patch clamp recordings demonstrated that G4 induced a 7.5-fold increment in capacitive currents as a measure of membrane permeability. Moreover, treatment with this dendrimer increased intracellular Ca2+ by 8-fold with a complete disruption of transients pattern, having as consequence that G4 treatment increased the synaptic vesicle release and frequency of synaptic events by 2.4- and 3-fold, respectively. PFO25 and PPEG25 treatments did not alter membrane permeability, total Ca2+ intake, synaptic vesicle release or synaptic activity frequency. These results demonstrate that cationic G4 dendrimers have neurotoxic effects and induce alterations in normal synaptic activity, which are generated by the augmentation of membrane permeability and a subsequent intracellular Ca2+ increase. Interestingly, these toxic effects and synaptic alterations are prevented by the modification of 25% of PAMAM surface with either folate or polyethylene glycol.

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

International Nuclear Information System (INIS)

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

2006-01-01

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

Fate and transformation products of amine-terminated PAMAM dendrimers under ozonation and irradiation

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Santiago-Morales, Javier; Rosal, Roberto; Hernando, María D.; Ulaszewska, Maria M.; García-Calvo, Eloy; Fernández-Alba, Amadeo R.

2014-01-01

Highlights: • We detected transformation products from dendrimer under ozonation and irradiation. • Retro-Michael fragmentation pathway with highly oxygenated structures. • High toxicity of G3 PAMAM dendrimer for green algae. • Reactive oxygen species were associated with the toxic damage. • Transformation mixtures could be more toxic than the parent dendrimer. -- Abstract: This article deals with the degradation of a third-generation (G3) poly(amidoamine) (PAMAM) dendrimer under ozonation and irradiation. The identification and quantification of G3 PAMAM dendrimer and its transformation products has been performed by liquid chromatography–electrospray ionization-hybrid quadrupole time-of-flight-mass spectrometry. The dendrimer was completely depleted by ozone in less than 1 min. The effect of ultraviolet irradiation was attributed to hydroxyl-mediated oxidation. The transformation products were attributed to the oxidation of amines, which resulted in highly oxidized structures with abundance of carboxylic acids, which started from the formation of amine oxide and the scission of the C-N bond of the amide group. We studied the toxicity of treated mixtures for six different organisms: the acute toxicity for the bacterium Vibrio fischeri and the microcrustacean Daphnia magna, the multigenerational growth inhibition of the alga Pseudokirchneriella subcapitata, and the seed germination phytotoxicity of Licopersicon esculentum, Lactuca sativa and Lolium perenne. Ozonation and irradiation originated transformation products are more toxic than the parent dendrimer. The toxicity of the dendrimer for the green alga was linked to a strong increase of intracellular reactive oxygen species with intense lipid peroxidation

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.

Use of poly (amidoamine dendrimer for dentinal tubule occlusion: a preliminary study.

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Tianda Wang

Full Text Available The occlusion of dentinal tubules is an effective method to alleviate the symptoms caused by dentin hypersensitivity, a significant health problem in dentistry and daily life. The in situ mineralization within dentinal tubules is a promising treatment for dentin hypersensitivity as it induces the formation of mineral on the sensitive regions and occludes the dentinal tubules. This study was carried out to evaluate the in vitro effect of a whole generation poly(amidoamine (PAMAM dendrimer (G3.0 on dentinal tubule occlusion by inducing mineralization within dentinal tubules. Dentin discs were treated with PAMAM dendrimers using two methods, followed by the in vitro characterization using Attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR, X-ray diffraction (XRD, Field emission scanning electron microscopy (FE-SEM and Energy-Dispersive X-ray Spectroscopy (EDS. These results showed that G3.0 PAMAM dendrimers coated on dentin surface and infiltrated in dentinal tubules could induce hydroxyapatite formation and resulted in effective dentinal tubule occlusion. Moreover, crosslinked PAMAM dendrimers could induce the remineralization of demineralized dentin and thus had the potential in dentinal tubule occlusion. In this in vitro study, dentinal tubules occlusion could be achieved by using PAMAM dendrimers. This could lead to the development of a new therapeutic technique for the treatment of dentin hypersensitivity.

Effect of addition of Proline, ionic liquid [Choline][Pro] on CO2 separation properties of poly(amidoamine) dendrimer / poly(ethylene glycol) hybrid membranes

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Duan, S. H.; Kai, T.; Chowdhury, F. A.; Taniguchi, I.; Kazama, S.

2018-01-01

Poly(amidoamine) (PAMAM) dendrimers were incorporated into cross-linked poly(ethylene glycol) (PEGDMA) matrix to improve carbon dioxide (CO2) separation performance at elevated pressures. In our previous studies, PAMAM/PEGDMA hybrid membranes showed high CO2 separation properties from CO2/H2 mixed gases. In this study, proline, choline and ionic liquid [Choline][Pro] compounds were selected as rate promoters that were used to prepare PAMAM/PEGDMA hybrid membranes. The effect of addition of proline, choline, IL [Choline][Pro] on separation performance of PAMAM/PEGDMA) hybrid membranes for CO2/H2 separation was investigated. Amino acid proline, choline, and IL [Choline][Pro] were used to promote CO2 and amine reaction. With the addition of [Choline][Pro] into PAMAM/PEG membrane, CO2 permeance of PAMAM/PEG hybrid membranes are increased up to 46% without any change of selectivity of membrane for CO2.

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

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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 ...

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

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

2015-11-01

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

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

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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

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

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

2016-07-25

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

Dendrimer-stabilized bismuth sulfide nanoparticles: synthesis, characterization, and potential computed tomography imaging applications.

Science.gov (United States)

Fang, Yi; Peng, Chen; Guo, Rui; Zheng, Linfeng; Qin, Jinbao; Zhou, Benqing; Shen, Mingwu; Lu, Xinwu; Zhang, Guixiang; Shi, Xiangyang

2013-06-07

We report here a general approach to synthesizing dendrimer-stabilized bismuth sulfide nanoparticles (Bi2S3 DSNPs) for potential computed tomography (CT) imaging applications. In this study, ethylenediamine core glycidol hydroxyl-terminated generation 4 poly(amidoamine) dendrimers (G4.NGlyOH) were used as stabilizers to first complex the Bi(III) ions, followed by reaction with hydrogen sulfide to generate Bi2S3 DSNPs. By varying the molar ratio of Bi atom to dendrimer, stable Bi2S3 DSNPs with an average size range of 5.2-5.7 nm were formed. The formed Bi2S3 DSNPs were characterized via different techniques. X-ray absorption coefficient measurements show that the attenuation of Bi2S3 DSNPs is much higher than that of iodine-based CT contrast agent at the same molar concentration of the active element (Bi versus iodine). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay and hemolysis assay reveal that the formed Bi2S3 DSNPs are noncytotoxic and have a negligible hemolysis effect in the studied concentration range. Furthermore, we show that cells incubated with the Bi2S3 DSNPs are able to be imaged using CT, a prominent enhancement at the point of rabbit injected subcutaneously with the Bi2S3 DSNPs is able to be visualized via CT scanning, and the mouse's pulmonary vein can be visualized via CT after intravenous injection of the Bi2S3 DSNPs. With the good biocompatibility, enhanced X-ray attenuation property, and tunable dendrimer chemistry, the designed Bi2S3 DSNPs should be able to be further functionalized, allowing them to be used as a highly efficient contrast agent for CT imaging of different biological systems.

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

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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.

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

Energy Technology Data Exchange (ETDEWEB)

Bodewein, Lambert [Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine and Pharmacology, Frankfurt & Aachen (Germany); Institute of Environmental Research (Biology V), RWTH Aachen University (Germany); Schmelter, Frank; Di Fiore, Stefano [Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Molecular Biology Division, Aachen (Germany); Hollert, Henner [Institute of Environmental Research (Biology V), RWTH Aachen University (Germany); Fischer, Rainer [Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine and Pharmacology, Frankfurt & Aachen (Germany); Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Molecular Biology Division, Aachen (Germany); Fenske, Martina, E-mail: martina.fenske@ime.fraunhofer.de [Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine and Pharmacology, Frankfurt & Aachen (Germany)

2016-08-15

Dendrimers are an emerging class of polymeric nanoparticles with beneficial biomedical applications like early diagnostics, in vitro gene transfection or controlled drug delivery. However, the potential toxic impact of exposure on human health or the environment is often inadequately defined. Thus, polyamidoamine (PAMAM) dendrimers of generations G3.0, 3.5, 4.0, 4.5 and 5.0 and polypropylenimine (PPI) dendrimers G3.0, 4.0 and 5.0 were tested in zebrafish embryos for 96 h and human cancer cell lines for 24 h, to assess and compare developmental in vivo toxicity with cytotoxicity. The zebrafish embryo toxicity of cationic PAMAM and PPI dendrimers increased over time, with EC50 values ranging from 0.16 to just below 1.7 μM at 24 and 48 hpf. The predominant effects were mortality, plus reduced heartbeat and blood circulation for PPI dendrimers. Apoptosis in the embryos increased in line with the general toxicity concentration-dependently. Hatch and dechorionation of the embryos increased the toxicity, suggesting a protective role of the chorion. Lower generation dendrimers were more toxic in the embryos whereas the toxicity in the HepG2 and DU145 cell lines increased with increasing generation of cationic PAMAMs and PPI dendrimers. HepG2 were less sensitive than DU145 cells, with IC50 values ≥ 402 μM (PAMAMs) and ≤ 240 μM (PPIs) for HepG2 and ≤ 13.24 μM (PAMAMs) and ≤ 12.84 μM (PPIs) for DU145. Neither in fish embryos nor cells toxicity thresholds were determinable for anionic PAMAM G3.5 and G4.5. The study demonstrated that the cytotoxicity underestimated the in-vivo toxicity of the dendrimers in the fish embryos. - Highlights: • Zebrafish embryo toxicity of cationic PAMAM and PPI dendrimers increased over time. • Zebrafish embryo toxicity of cationic dendrimers did not increase with generation. • Cationic dendrimers induced apoptosis in zebrafish embryos. • Toxicity of cationic dendrimers was lower in HepG2 and DU145 than zebrafish embryos. �

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

International Nuclear Information System (INIS)

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

2016-01-01

Dendrimers are an emerging class of polymeric nanoparticles with beneficial biomedical applications like early diagnostics, in vitro gene transfection or controlled drug delivery. However, the potential toxic impact of exposure on human health or the environment is often inadequately defined. Thus, polyamidoamine (PAMAM) dendrimers of generations G3.0, 3.5, 4.0, 4.5 and 5.0 and polypropylenimine (PPI) dendrimers G3.0, 4.0 and 5.0 were tested in zebrafish embryos for 96 h and human cancer cell lines for 24 h, to assess and compare developmental in vivo toxicity with cytotoxicity. The zebrafish embryo toxicity of cationic PAMAM and PPI dendrimers increased over time, with EC50 values ranging from 0.16 to just below 1.7 μM at 24 and 48 hpf. The predominant effects were mortality, plus reduced heartbeat and blood circulation for PPI dendrimers. Apoptosis in the embryos increased in line with the general toxicity concentration-dependently. Hatch and dechorionation of the embryos increased the toxicity, suggesting a protective role of the chorion. Lower generation dendrimers were more toxic in the embryos whereas the toxicity in the HepG2 and DU145 cell lines increased with increasing generation of cationic PAMAMs and PPI dendrimers. HepG2 were less sensitive than DU145 cells, with IC50 values ≥ 402 μM (PAMAMs) and ≤ 240 μM (PPIs) for HepG2 and ≤ 13.24 μM (PAMAMs) and ≤ 12.84 μM (PPIs) for DU145. Neither in fish embryos nor cells toxicity thresholds were determinable for anionic PAMAM G3.5 and G4.5. The study demonstrated that the cytotoxicity underestimated the in-vivo toxicity of the dendrimers in the fish embryos. - Highlights: • Zebrafish embryo toxicity of cationic PAMAM and PPI dendrimers increased over time. • Zebrafish embryo toxicity of cationic dendrimers did not increase with generation. • Cationic dendrimers induced apoptosis in zebrafish embryos. • Toxicity of cationic dendrimers was lower in HepG2 and DU145 than zebrafish embryos. �

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

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

2010-01-01

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

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

International Nuclear Information System (INIS)

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

2010-01-01

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

Effect of Mass Transport in the Synthesis of Partially Acetylated Dendrimer: Implications for Functional Ligand–Nanoparticle Distributions

OpenAIRE

Mullen, Douglas G.; Borgmeier, Emilee L.; Fang, Ming; McNerny, Daniel Q.; Desai, Ankur; Baker, James R.; Orr, Bradford G.; Holl, Mark M. Banaszak

2010-01-01

Partial acetylation of the amine-terminated poly(amidoamine) dendrimer has been used in the preparation of dendrimer particles conjugated with a wide variety of functional ligands including targeting moieties, therapeutic agents, and dye molecules. The effectiveness of mass transport during the partial acetylation reaction was found to have a major effect on subsequent distributions of dendrimer–ligand components and to be a major source of inconsistency between batches. This study has broad ...

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

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Scott D Swanson

2008-06-01

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

Endocytic Uptake, Transport and Macromolecular Interactions of Anionic PAMAM Dendrimers within Lung Tissue.

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Morris, Christopher J; Aljayyoussi, Ghaith; Mansour, Omar; Griffiths, Peter; Gumbleton, Mark

2017-12-01

Polyamidoamine (PAMAM) dendrimers are a promising class of nanocarrier with applications in both small and large molecule drug delivery. Here we report a comprehensive evaluation of the uptake and transport pathways that contribute to the lung disposition of dendrimers. Anionic PAMAM dendrimers and control dextran probes were applied to an isolated perfused rat lung (IPRL) model and lung epithelial monolayers. Endocytosis pathways were examined in primary alveolar epithelial cultures by confocal microscopy. Molecular interactions of dendrimers with protein and lipid lung fluid components were studied using small angle neutron scattering (SANS). Dendrimers were absorbed across the intact lung via a passive, size-dependent transport pathway at rates slower than dextrans of similar molecular sizes. SANS investigations of concentration-dependent PAMAM transport in the IPRL confirmed no aggregation of PAMAMs with either albumin or dipalmitoylphosphatidylcholine lung lining fluid components. Distinct endocytic compartments were identified within primary alveolar epithelial cells and their functionality in the rapid uptake of fluorescent dendrimers and model macromolecular probes was confirmed by co-localisation studies. PAMAM dendrimers display favourable lung biocompatibility but modest lung to blood absorption kinetics. These data support the investigation of dendrimer-based carriers for controlled-release drug delivery to the deep lung.

RGD peptide-modified multifunctional dendrimer platform for drug encapsulation and targeted inhibition of cancer cells.

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He, Xuedan; Alves, Carla S; Oliveira, Nilsa; Rodrigues, João; Zhu, Jingyi; Bányai, István; Tomás, Helena; Shi, Xiangyang

2015-01-01

Development of multifunctional nanoscale drug-delivery systems for targeted cancer therapy still remains a great challenge. Here, we report the synthesis of cyclic arginine-glycine-aspartic acid (RGD) peptide-conjugated generation 5 (G5) poly(amidoamine) dendrimers for anticancer drug encapsulation and targeted therapy of cancer cells overexpressing αvβ3 integrins. In this study, amine-terminated G5 dendrimers were used as a platform to be sequentially modified with fluorescein isothiocyanate (FI) via a thiourea linkage and RGD peptide via a polyethylene glycol (PEG) spacer, followed by acetylation of the remaining dendrimer terminal amines. The developed multifunctional dendrimer platform (G5.NHAc-FI-PEG-RGD) was then used to encapsulate an anticancer drug doxorubicin (DOX). We show that approximately six DOX molecules are able to be encapsulated within each dendrimer platform. The formed complexes are water-soluble, stable, and able to release DOX in a sustained manner. One- and two-dimensional NMR techniques were applied to investigate the interaction between dendrimers and DOX, and the impact of the environmental pH on the release rate of DOX from the dendrimer/DOX complexes was also explored. Furthermore, cell biological studies demonstrate that the encapsulation of DOX within the G5.NHAc-FI-PEG-RGD dendrimers does not compromise the anticancer activity of DOX and that the therapeutic efficacy of the dendrimer/DOX complexes is solely related to the encapsulated DOX drug. Importantly, thanks to the role played by RGD-mediated targeting, the developed dendrimer/drug complexes are able to specifically target αvβ3 integrin-overexpressing cancer cells and display specific therapeutic efficacy to the target cells. The developed RGD peptide-targeted multifunctional dendrimers may thus be used as a versatile platform for targeted therapy of different types of αvβ3 integrin-overexpressing cancer cells. Copyright © 2014 Elsevier B.V. All rights reserved.

Lactose-containing starburst dendrimers: influence of dendrimer generation and binding-site orientation of receptors (plant/animal lectins and immunoglobulins) on binding properties.

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André, S; Ortega, P J; Perez, M A; Roy, R; Gabius, H J

1999-11-01

Starburst glycodendrimers offer the potential to serve as high-affinity ligands for clinically relevant sugar receptors. In order to define areas of application, their binding behavior towards sugar receptors with differential binding-site orientation but identical monosaccharide specificity must be evaluated. Using poly(amidoamine) starburst dendrimers of five generations, which contain the p-isothiocyanato derivative of p-aminophenyl-beta-D-lactoside as ligand group, four different types of galactoside-binding proteins were chosen for this purpose, i.e., the (AB)(2)-toxic agglutinin from mistletoe, a human immunoglobulin G fraction, the homodimeric galectin-1 with its two binding sites at opposite ends of the jelly-roll-motif-harboring protein and monomeric galectin-3. Direct solid-phase assays with surface-immobilized glycodendrimers resulted in obvious affinity enhancements by progressive core branching for the plant agglutinin and less pronounced for the antibody and galectin-1. High density of binding of galectin-3 with modest affinity increases only from the level of the 32-mer onwards points to favorable protein-protein interactions of the monomeric lectin and a spherical display of the end groups without a major share of backfolding. When the inhibitory potency of these probes was evaluated as competitor of receptor binding to an immobilized neoglycoprotein or to asialofetuin, a marked selectivity was detected. The 32- and 64-mers were second to none as inhibitors for the plant agglutinin against both ligand-exposing matrices and for galectin-1 on the matrix with a heterogeneous array of interglycoside distances even on the per-sugar basis. In contrast, a neoglycoprotein with the same end group was superior in the case of the antibody and, less pronounced, monomeric galectin-3. Intimate details of topological binding-site presentation and the ligand display on different generations of core assembly are major operative factors which determine the potential

On-Demand Bioadhesive Dendrimers with Reduced Cytotoxicity

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Feng Gao

2018-03-01

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

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

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

2017-07-15

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

Development of Tat-Conjugated Dendrimer for Transdermal DNA Vaccine Delivery.

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Bahadoran, Azadeh; Moeini, Hassan; Bejo, Mohd Hair; Hussein, Mohd Zobir; Omar, Abdul Rahman

In order to enhance cellular uptake and to facilitate transdermal delivery of DNA vaccine, polyamidoamine (PAMAM) dendrimers conjugated with HIV transactivator of transcription (TAT) was developed. First, the plasmid DNA (pIRES-H5/GFP) nanoparticle was formulated using PAMAM dendrimer and TAT peptide and then characterized for surface charge, particle size, DNA encapsulation and protection of the pIRES-H5/GFP DNA plasmid to enzymatic digestion. Subsequently, the potency of the TAT-conjugated dendrimer for gene delivery was evaluated through in vitro transfection into Vero cells followed by gene expression analysis including western blotting, fluorescent microscopy and PCR. The effect of the TAT peptide on cellular uptake of DNA vaccine was studied by qRT-PCR and flow cytometry. Finally, the ability of TAT-conjugated PAMAM dendrimer for transdermal delivery of the DNA plasmid was assessed through artificial membranes followed by qRT-PCR and flow cytometry. TAT-conjugated PAMAM dendrimer showed the ability to form a compact and nanometre-sized polyplexes with the plasmid DNA, having the size range of 105 to 115 nm and a positive charge of +42 to +45 mV over the N/P ratio of 6:1(+/-).  In vitro transfection analysis into Vero cells confirms the high potency of TAT-conjugated PAMAM dendrimer to enhance the cellular uptake of DNA vaccine.  The permeability value assay through artificial membranes reveals that TAT-conjugated PAMAM has more capacity for transdermal delivery of the DNA compared to unmodified PAMAM dendrimer (Pdendrimer is a promising non-viral vector for transdermal use.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

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

International Nuclear Information System (INIS)

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

2009-01-01

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

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

Science.gov (United States)

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

2014-01-07

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

Developmental toxicity of low generation PAMAM dendrimers in zebrafish

International Nuclear Information System (INIS)

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

2007-01-01

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

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

Science.gov (United States)

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

2011-10-01

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

Effect of methotrexate conjugated PAMAM dendrimers on the viability of MES-SA uterine cancer cells

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Samreen Khatri

2014-01-01

Full Text Available The aim of this work was to synthesize methotrexate (MTX-polyamidoamine (PAMAM dendritic nanoconjugates and to study their effect on cell viability in uterine sarcoma cells. The amide-bonded PAMAM dendrimer-MTX conjugates were prepared by conjugation between the amine-terminated G5 dendrimer and the carboxylic groups of the MTX using a dicyclohexylcarbodiimide coupling reaction. The formation of conjugates was evaluated by ultraviolet (UV and 1 H nuclear magnetic resonance ( 1 H NMR spectroscopy studies. The cell survival of MES-SA cells, a uterine sarcoma cell line, was evaluated in the presence of the dendrimer-MTX nanoconjugate, using appropriate controls. The UV and 1 H NMR study confirmed the formation of covalent bonds between the drug and the dendrimer. The cell viability study indicated that the nanoconjugates had significantly improved cell killing compared to the free MTX.

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

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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

Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy.

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Narsireddy, Amreddy; Vijayashree, Kurra; Adimoolam, Mahesh G; Manorama, Sunkara V; Rao, Nalam M

2015-01-01

Challenges in photodynamic therapy (PDT) include development of efficient near infrared-sensitive photosensitizers (5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphine [PS]) and targeted delivery of PS to the tumor tissue. In this study, a dual functional dendrimer was synthesized for targeted PDT. For targeting, a poly(amidoamine) dendrimer (G4) was conjugated with a PS and a nitrilotriacetic acid (NTA) group. A peptide specific to human epidermal growth factor 2 was expressed in Escherichia coli with a His-tag and was specifically bound to the NTA group on the dendrimer. Reaction conditions were optimized to result in dendrimers with PS and the NTA at a fractional occupancy of 50% and 15%, respectively. The dendrimers were characterized by nuclear magnetic resonance, matrix-assisted laser desorption/ionization, absorbance, and fluorescence spectroscopy. Using PS fluorescence, cell uptake of these particles was confirmed by confocal microscopy and fluorescence-activated cell sorting. PS-dendrimers are more efficient than free PS in PDT-mediated cell death assays in HER2 positive cells, SK-OV-3. Similar effects were absent in HER2 negative cell line, MCF-7. Compared to free PS, the PS-dendrimers have shown significant tumor suppression in a xenograft animal tumor model. Conjugation of a PS with dendrimers and with a targeting agent has enhanced photodynamic therapeutic effects of the PS.

Cellular internalization and transport of biodegradable polyester dendrimers on a model of the pulmonary epithelium and their formulation in pressurized metered-dose inhalers.

Science.gov (United States)

Heyder, Rodrigo S; Zhong, Qian; Bazito, Reinaldo C; da Rocha, Sandro R P

2017-03-30

The purpose of this study was to evaluate the effect of generation and surface PEGylation of degradable polyester-based dendrimers nanocarriers on their interactions with an in vitro model of the pulmonary epithelium as well as to assess the ability to formulate such carriers in propellant-based, portable oral-inhalation devices to determine their potential for local and systemic delivery of drugs to and through the lungs. Hydroxyl (-OH) terminated polyester dendrimers of generation 3 and 4 (G3, and G4) were synthesized using a divergent approach. G4 was surface-modified with PEG (1,000Da). All dendrimers and their building blocks were determined to be highly compatible with the model pulmonary epithelium, with toxicity profiles much more favorable than non-degradable polyamidoamine dendrimers (PAMAM). The transport of the species from the apical to basolateral side across polarized Calu-3 monolayers showed to be generation and surface-chemistry (PEGylation) dependent. The extent of the transport is modulated by their interaction with the polarized epithelium and their transient opening of the tight junctions. G3 was the one most efficiently internalized by the epithelium, and had a small impact on the integrity of the monolayer. On the other hand, the PEGylated G4 was the one least internalized by the polarized epithelium, and at the same time had a more pronounced transient impact on the cellular junctions, resulting in more efficient transport across the cell monolayer. PEGylation of the dendrimer surface played other roles as well. PEGylation modulated the degradation profile of the dendrimer, slowing the process in a step-wise fashion - first the PEG layer is shed and then the dendrimer starts degrading. PEGylation also helped increase the solvation of the nanocarriers by the hydrofluoroalkane propellant used in pressurized metered-dose inhalers, resulting in formulations with excellent dispersibility and aerosol quality (deep lung deposition of 88

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

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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.

Dendrimer-assisted controlled growth of carbon nanotubes for enhanced thermal interface conductance

International Nuclear Information System (INIS)

Amama, Placidus B; Cola, Baratunde A; Sands, Timothy D; Xu, Xianfan; Fisher, Timothy S

2007-01-01

Multi-walled carbon nanotubes (MWCNTs) with systematically varied diameter distributions and defect densities were reproducibly grown from a modified catalyst structure templated in an amine-terminated fourth-generation poly(amidoamine) (PAMAM) dendrimer by microwave plasma-enhanced chemical vapor deposition. Thermal interface resistances of the vertically oriented MWCNT arrays as determined by a photoacoustic technique reveal a strong correlation with the quality as assessed by Raman spectroscopy. This study contributes not only to the development of an active catalyst via a wet chemical route for structure-controlled MWCNT growth, but also to the development of efficient and low-cost MWCNT-based thermal interface materials with thermal interface resistances ≤10 mm 2 K W -1

Controllable synthesis of hydroxyapatite nanocrystals via a dendrimer-assisted hydrothermal process

International Nuclear Information System (INIS)

Zhou Zhuohua; Zhou, Ping-Le; Yang Shiping; Yu Xibin; Yang Liangzhun

2007-01-01

The morphology and size of hydroxyapatite Ca 10 (PO 4 ) 6 (OH) 2 (denoted HAP) can be controlled under hydrothermal treatment assisted with different dendrimers, such as carboxylic terminated poly(amidoamine) (PAMAM) and polyhydroxy terminated PAMAM. The structure and morphology were characterized by X-ray diffraction (XRD), infrared spectroscopy (IR) and transmission electron microscopy (TEM). IR spectra were also used to investigate the complexation of Ca 2+ with PAMAM. The results revealed that the inner cores of the PAMAM dendrimers are hydrophilic and potentially open to calcium ions, since interior nitrogen moieties serve as complexation sites, especially in case of the polyhydroxy terminated PAMAM. And the reasonable mechanism of crystallization was proposed that it can be attributed to the localization of nucleation site: external or interior PAMAM. Additionally, the PAMAM dendrimer with carboxylic and polyhydroxy groups has an effective influence on the size and shape of hydroxyapatite (HAP) nanostructures. Different crystal morphology was accomplished by adsorption of different dendrimers onto specific faces of growing crystals, altering the relative growth rates of the different crystallographic faces and leading to different crystal habits

In vitro evaluation of dendrimer prodrugs for oral drug delivery.

Science.gov (United States)

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

2007-05-04

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

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

International Nuclear Information System (INIS)

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

2016-01-01

Highlights: • Methylene blue(MB)-labelled 3 G dendrimers electronically wire flavoenzymes to graphite electrodes. • Dendrimer-templated organization of MB improves electron transfer efficiency. • Covalent attachment of dendrimers to graphite provides stability of binding superior to S-Au. • Sugar-oxidizing hexose oxidase can be wired with no loss of FAD and electrocatalytic activity. - Abstract: Electro-enzymatic biotransformation requires an efficient and robust electronic communication between the biomolecules and electrodes, often performed by the relevant electron transfer (ET) mediating systems. Of those, redox-labeled dendrimeric structures, biocompatible and bearing spatially ordered multiple redox centers, represent an advanced alternative to the existing approaches. Here we show that methylene blue (MB)-labeled G3 PAMAM dendrimers covalently attached to the high-surface area spectroscopic graphite (Gr) electrodes form stable and spatially resolved electronic wires, characterized by the heterogeneous ET rate constant of 7.1 ± 0.1 s"−"1; they can be used for electronic wiring of glucose-oxidizing FAD-containing enzymes, such as hexose oxidase (HOX), and further bioelectrocatalysis of glucose oxidation, starting, at pH 7, from -100 mV vs. Ag/AgCl. Thus, dendrimer-templated electronic wires, comprising MB molecules conjugated to the periphery of the PAMAM and anchored to the surface of cost-effective Gr electrodes represent an efficient and robust tool for protein wiring to electrodes for their perspective bioelectronic applications in biosensors and biofuel cells.

Wiring of heme enzymes by methylene-blue labeled dendrimers

DEFF Research Database (Denmark)

Álvarez-Martos, Isabel; Shahdost-fard, Faezeh; Ferapontova, Elena

2017-01-01

Redox-modified branched 3D dendrimeric nanostructures may be considered as perspective wires for electrical connection between redox enzymes and electrodes. Here, we studied electron transfer (ET) reactions and bioelectrocatalysis of heme-containing horseradish peroxidase (HRP) and heme- and moli......Redox-modified branched 3D dendrimeric nanostructures may be considered as perspective wires for electrical connection between redox enzymes and electrodes. Here, we studied electron transfer (ET) reactions and bioelectrocatalysis of heme-containing horseradish peroxidase (HRP) and heme......- and molibdopterin-containing sulfite oxidase (SOx), wired to gold by the methylene blue (MB)-labeled polyamidoamine (PAMAM) dendrimers. The enzymes’ electrochemical transformation and bioelectrocatalytic function could be followed at both unlabeled and MB-labeled dendrimer-modified electrodes with the formal redox......, optimization of bioelectrocatalysis of complex intermembrane and, possibly, membrane enzymes....

A new approach in the preparation of dendrimer-based bifunctional diethylenetriaminepentaacetic acid MR contrast agent derivatives.

Science.gov (United States)

Nwe, Kido; Xu, Heng; Regino, Celeste Aida S; Bernardo, Marcelino; Ileva, Lilia; Riffle, Lisa; Wong, Karen J; Brechbiel, Martin W

2009-07-01

In this paper, we report a new method to prepare and characterize a contrast agent based on a fourth-generation (G4) polyamidoamine (PAMAM) dendrimer conjugated to the gadolinium complex of the bifunctional diethylenetriamine pentaacetic acid derivative (1B4M-DTPA). The method involves preforming the metal-ligand chelate in alcohol prior to conjugation to the dendrimer. The dendrimer-based agent was purified by a Sephadex G-25 column and characterized by elemental analysis. The analysis and SE-HPLC data gave a chelate to dendrimer ratio of 30:1 suggesting conjugation at approximately every other amine terminal on the dendrimer. Molar relaxivity of the agent measured at pH 7.4 displayed a higher value than that of the analogous G4 dendrimer based agent prepared by the postmetal incorporation method (r(1) = 26.9 vs 13.9 mM(-1) s(-1) at 3 T and 22 degrees C). This is hypothesized to be due to the higher hydrophobicity of this conjugate and the lack of available charged carboxylate groups from noncomplexed free ligands that might coordinate to the metal and thus also reduce water exchange sites. Additionally, the distribution populations of compounds that result from the postmetal incorporation route are eliminated from the current product simplifying characterization as quality control issues pertaining to the production of such agents for clinical use as MR contrast agents. In vivo imaging in mice showed a reasonably fast clearance (t(1/2) = 24 min) suggesting a viable agent for use in clinical application.

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

Energy Technology Data Exchange (ETDEWEB)

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

2010-01-01

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

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

International Nuclear Information System (INIS)

Ilaiyaraja, P.; Ashish Kumar Singha Deb; Ponraju, D.

2015-01-01

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

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

Science.gov (United States)

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

2018-04-13

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

Control of mobility in molecular organic semiconductors by dendrimer generation

Science.gov (United States)

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

2001-04-01

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

Nondispersive hole transport in a spin-coated dendrimer film measured by the charge-generation-layer time-of-flight method

Science.gov (United States)

Markham, Jonathan P. J.; Anthopoulos, Thomas D.; Samuel, Ifor D. W.; Richards, Gary J.; Burn, Paul L.; Im, Chan; Bassler, Heinz

2002-10-01

Measurements of the mobility of a first-generation (G1) bis-fluorene cored dendrimer have been performed on spin-coated samples of 500 nm thickness using the charge-generation-layer time-of-flight (TOF) technique. A 10 nm perylene charge generation layer was excited by the 532 nm line of a Q-switched Nd:YAG laser and the generated carriers swept through the dendrimer film under an applied field. We observe nondispersive hole transport in the dendrimer layer with a room-temperature mobility mu=2.0 x10-4 cm2/V s at a field of 0.55 MV/cm. There is a weak field dependence of the mobility and it increases from mu=1.6 x10-4 cm2/V s at 0.2 MV/cm to mu=3.0 x10-4 cm2/V s at 1.4 MV/cm. These results suggest that the measurement of mobility by TOF in spin-coated samples on thickness scales relevant to organic light-emitting diodes can yield valuable information, and that dendrimers are promising materials for device applications.

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

Science.gov (United States)

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

2015-08-15

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

pH and generation dependent morphologies of PAMAM dendrimers on a graphene substrate.

Science.gov (United States)

Gosika, Mounika; Maiti, Prabal K

2018-03-07

The adsorption of PAMAM dendrimers at solid/water interfaces has been extensively studied, and is mainly driven by electrostatic and van der Waals interactions between the substrate and the dendrimers. However, the pH dependence of the adsorption driven predominantly by the van der Waals interactions is poorly explored, although it is crucial for investigating the potentiality of these dendrimers in supercapacitors and surface patterning. Motivated by this aspect, we have studied the adsorption behavior of PAMAM dendrimers of generations 2 (G2) to 5 (G5) with pH and salt concentration variation, on a charge neutral graphene substrate, using fully atomistic molecular dynamics simulations. The instantaneous snapshots from our simulations illustrate that the dendrimers deform significantly from their bulk structures. Based on various structural property calculations, we classify the adsorbed dendrimer morphologies into five categories and map them to a phase diagram. Interestingly, the morphologies we report here have striking analogies with those reported in star-polymer adsorption studies. From the fractional contacts and other structural property analyses we find that the deformations are more pronounced at neutral pH as compared to high and low pH. Higher generation dendrimers resist deformation following the deformation trend, G2 > G3 > G4 > G5 at any given pH level. As the adsorption here is mainly driven by van der Waals interactions, we observe no desorption of the dendrimers as the salt molarity is increased, unlike that reported in the electrostatically driven adsorption studies.

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. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Practical computational toolkits for dendrimers and dendrons structure design

Science.gov (United States)

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

2017-09-01

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

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

National Research Council Canada - National Science Library

Shibaev, V

1998-01-01

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

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.

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

Science.gov (United States)

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

2010-02-08

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

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

Dendrimer-driven neurotrophin expression differs in temporal patterns between rodent and human stem cells.

Science.gov (United States)

Shakhbazau, Antos; Shcharbin, Dzmitry; Seviaryn, Ihar; Goncharova, Natalya; Kosmacheva, Svetlana; Potapnev, Mihail; Bryszewska, Maria; Kumar, Ranjan; Biernaskie, Jeffrey; Midha, Rajiv

2012-05-07

This study reports the use of a nonviral expression system based on polyamidoamine dendrimers for time-restricted neurotrophin overproduction in mesenchymal stem cells and skin precursor-derived Schwann cells. The dendrimers were used to deliver plasmids for brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3) expression in both rodent and human stem cells, and the timelines of expression were studied. We have found that, despite the fact that transfection efficiencies and protein expression levels were comparable, dendrimer-driven expression in human mesenchymal stem cells was characterized by a more rapid decline compared to rodent cells. Transient expression systems can be beneficial for some neurotrophins, which were earlier reported to cause unwanted side effects in virus-based long-term expression models. Nonviral neurotrophin expression is a biologically safe and accessible alternative to increase the therapeutic potential of autologous adult stem cells and stem cell-derived functional differentiated cells.

Interactions and encapsulation of vitamins C, B3, and B6 with dendrimers in water.

Science.gov (United States)

Boisselier, Elodie; Liang, Liyuan; Dalko-Csiba, Maria; Ruiz, Jaime; Astruc, Didier

2010-05-25

Titrations of commercial diaminobutane (DAB) and polyamidoamine (PAMAM) dendrimers by vitamins C (ascorbic acid, AA), B(3) (nicotinic acid), and B(6) (pyridoxine) were monitored by (1)H NMR spectroscopy using the chemical shifts of both dendrimer and vitamin protons and analyzed by comparison with the titration of propylamine. Quaternarizations of the terminal primary amino groups and intradendritic tertiary amino groups, which are nearly quantitative with vitamin C, were characterized by more or less sharp variations (Deltadelta) of the (1)H chemical shift (delta) at the equivalence points. The peripheral primary amino groups of the DAB dendrimers were quaternarized first, but not selectively, whereas a sharp chemical-shift variation was recorded for the inner methylene protons near the tertiary amines, thereby indicating encapsulation, when all the dendritic amines were quaternarized. With DAB-G5-64-NH(2), some excess acid is required to protonate the inner amino groups, presumably because of basicity decrease due to excess charge repulsion. On the other hand, this selectivity was not observed with PAMAM dendrimers. The special case of the titration of the dendrimers by vitamin B(6) indicates only dominant supramolecular hydrogen-bonding interactions and no quaternarization, with core amino groups being privileged, which indicates the strong tendency to encapsulate vitamins. With vitamin B(3), a carboxylic acid, titration of DAB-G3-16-NH(2) shows that only six peripheral amino groups are protonated on average, even with excess vitamin B(3), because protonation is all the more difficult due to increased charge repulsion, as positive charges accumulate around the dendrimer. Inner amino groups interact with this vitamin, however, thus indicating encapsulation presumably with supramolecular hydrogen bonding without much charge transfer.

Effect of mannose targeting of hydroxyl PAMAM dendrimers on cellular and organ biodistribution in a neonatal brain injury model.

Science.gov (United States)

Sharma, Anjali; Porterfield, Joshua E; Smith, Elizabeth; Sharma, Rishi; Kannan, Sujatha; Kannan, Rangaramanujam M

2018-06-05

Neurotherapeutics for the treatment of central nervous system (CNS) disorders must overcome challenges relating to the blood-brain barrier (BBB), brain tissue penetration, and the targeting of specific cells. Neuroinflammation mediated by activated microglia is a major hallmark of several neurological disorders, making these cells a desirable therapeutic target. Building on the promise of hydroxyl-terminated generation four polyamidoamine (PAMAM) dendrimers (D4-OH) for penetrating the injured BBB and targeting activated glia, we explored if conjugation of targeting ligands would enhance and modify brain and organ uptake. Since mannose receptors [cluster of differentiation (CD) 206] are typically over-expressed on injured microglia, we conjugated mannose to the surface of multifunctional D4-OH using highly efficient, atom-economical, and orthogonal Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) click chemistry and evaluated the effect of mannose conjugation on the specific cell uptake of targeted and non-targeted dendrimers both in vitro and in vivo. In vitro results indicate that the conjugation of mannose as a targeting ligand significantly changes the mechanism of dendrimer internalization, giving mannosylated dendrimer a preference for mannose receptor-mediated endocytosis as opposed to non-specific fluid phase endocytosis. We further investigated the brain uptake and biodistribution of targeted and non-targeted fluorescently labeled dendrimers in a maternal intrauterine inflammation-induced cerebral palsy (CP) rabbit model using quantification methods based on fluorescence spectroscopy and confocal microscopy. We found that the conjugation of mannose modified the distribution of D4-OH throughout the body in this neonatal rabbit CP model without lowering the amount of dendrimer delivered to injured glia in the brain, even though significantly higher glial uptake was not observed in this model. Mannose conjugation to the dendrimer modifies the dendrimer

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

OpenAIRE

Nomani, Alireza; Haririan, Ismaeil; Rahimnia, Ramin; Fouladdel, Shamileh; Gazori, Tarane; Dinarvand, Rassoul; Omidi, Yadollah; Azizi, Ebrahim

2010-01-01

To gain a deeper understanding of the physicochemical phenomenon of self-assembled nanoparticles of different generations and ratios of poly (amidoamine) dendrimer (PAMAM) dendrimer and a short-stranded DNA (antisense oligonucleotide), multiple methods were used to characterize these nanoparticles including photon correlation spectroscopy (PCS); zeta potential measurement; and atomic force microscopy (AFM). PCS and AFM results revealed that, in contrast to larger molecules of DNA, smaller mol...

Fabrication and characterization of dendrimer-functionalized nano-hydroxyapatite and its application in dentin tubule occlusion.

Science.gov (United States)

Lin, Xuandong; Xie, Fangfang; Ma, Xueling; Hao, Yuhong; Qin, Hejia; Long, Jindong

2017-06-01

The occlusion of dentinal tubules is an effective method to alleviate the symptoms of dentin hypersensitivity. In this paper, we successfully modified nano-hydroxyapatite (n-HAP) with carboxyl-terminated polyamidoamine dendrimers by an aqueous-based chemical method and verified by fourier transform infrared spectroscopy (FTIR) and transmission electron microscope (TEM). Then the demineralization dentin discs were randomly divided into 4 groups, corresponding to subsequent brushing experiments: deionized water and kept in artificial saliva (AS), dendrimer-functionalized n-HAP and stored in AS, n-HAP and saved in AS, dendrimer-functionalized n-HAP and stored in deionized water. After 7 days of simulated brushing, dentin discs followed the in vitro characterization using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy and microhardness test. These data suggested that dendrimer-functionalized n-HAP could crosslink with collagen fibers and resulted in effective dentinal tubule occlusion. Moreover, the new material can induce the HAP formation with the help of superficial carboxyl and fill the spaces in dentinal tubules furtherly. The microhardness of dendrimer-functionalized n-HAP-treated specimens was significantly higher than others. In summary, dendrimer-functionalized n-HAP can be a new therapeutic material for the treatment of dentin hypersensitivity.

Structure of Carbon Nanotube-dendrimer composite

OpenAIRE

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

2012-01-01

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

Peptide Dendrimer/Lipid Hybrid Systems Are Efficient DNA Transfection Reagents: Structure–Activity Relationships Highlight the Role of Charge Distribution Across Dendrimer Generations

Science.gov (United States)

2013-01-01

Efficient DNA delivery into cells is the prerequisite of the genetic manipulation of organisms in molecular and cellular biology as well as, ultimately, in nonviral gene therapy. Current reagents, however, are relatively inefficient, and structure–activity relationships to guide their improvement are hard to come by. We now explore peptide dendrimers as a new type of transfection reagent and provide a quantitative framework for their evaluation. A collection of dendrimers with cationic and hydrophobic amino acid motifs (such as KK, KA, KH, KL, and LL) distributed across three dendrimer generations was synthesized by a solid-phase protocol that provides ready access to dendrimers in milligram quantities. In conjunction with a lipid component (DOTMA/DOPE), the best reagent, G1,2,3-KL ((LysLeu)8(LysLysLeu)4(LysLysLeu)2LysGlySerCys-NH2), improves transfection by 6–10-fold over commercial reagents under their respective optimal conditions. Emerging structure–activity relationships show that dendrimers with cationic and hydrophobic residues distributed in each generation are transfecting most efficiently. The trigenerational dendritic structure has an advantage over a linear analogue worth up to an order of magnitude. The success of placing the decisive cationic charge patterns in inner shells rather than previously on the surface of macromolecules suggests that this class of dendrimers significantly differs from existing transfection reagents. In the future, this platform may be tuned further and coupled to cell-targeting moieties to enhance transfection and cell specificity. PMID:23682947

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

Counterion Association and Structural Conformation Change of Charged PAMAM Dendrimer in Aqueous Solutions Revealed by Small Angle Neutron Scattering

International Nuclear Information System (INIS)

Chen, Wei-Ren

2009-01-01

Our previous study of the structure change of poly(amidoamine) starburst dendrimers (PAMAM) dendrimer of generation 5 (G5) have demonstrated that although the overall molecular size is practically unaffected by increasing DCl concentration, a configurational transformation, from a diffusive density profile to a more uniform density distribution, is clearly observed. In the current paper, the focus is placed on understanding the effect of counterion identity on the inter-molecular structure and the conformational properties by studying the effect due to DBr using small angle neutron scattering (SANS) and integral equation theory. While the overall molecular size is found to be essentially unaffected by the change in the pD of solutions, it is surprising that the intra-molecular configurational transformation is not observed when DBr is used. The overall effective charge of a dendrimer is nearly the same for 1, the effect of counterion identity becomes significant, the effective charge carried by a charged G5 PAPAM protonated by DBr becomes smaller than that of solutions with DCl. As a consequence, a counterion identity dependence of counterion association is revealed: Under the same level of molecular protonation, the specific counterion association, which is defined as the ratio of bound chloride anions to positively charged amines per molecule, is larger for the G5 PAMAM dendrimer charged by DBr than the one by DCl.

Surface functionality affects the biodistribution and microglia-targeting of intra-amniotically delivered dendrimers.

Science.gov (United States)

Zhang, Fan; Nance, Elizabeth; Zhang, Zhi; Jasty, Venkatasai; Kambhampati, Siva P; Mishra, Manoj K; Burd, Irina; Romero, Roberto; Kannan, Sujatha; Kannan, Rangaramanujam M

2016-09-10

Cerebral Palsy (CP) is a chronic childhood disorder with limited therapeutic options. Maternal intrauterine inflammation/infection is a major risk factor in the pathogenesis of CP. In pre-clinical models, dendrimer-based therapies are viable in postnatal period, attenuating inflammation and improving motor function in vivo. However, treatment to the mother, in the prenatal period, may provide the possibility of preventing/resolving inflammation at early stages. Towards this goal, we used a maternal intrauterine inflammation-induced rabbit model of CP to study fetal-maternal transport and neuroinflammation targeting of intra-amniotically administrated dendrimers with neutral/anionic surface functionality. Our study suggested both hydroxyl-terminated 'neutral' (D-OH) and carboxyl-terminated 'anionic' (D-COOH) Polyamidoamine (PAMAM) dendrimers were absorbed by fetuses and demonstrated bi-directional transport between fetuses and mother. D-OH was more effective in crossing the fetal blood-brain barrier, and targeting activated microglia. The cell-specific targeting was associated with the extent of microglia activation. This study demonstrated intra-amniotically administered hydroxyl PAMAM dendrimers could be an effective drug delivery vehicle for targeting fetal inflammation and preventing subsequent neurologic injury associated with chorioamnionitis. Copyright © 2016 Elsevier B.V. All rights reserved.

Polyphenylene dendrimers

International Nuclear Information System (INIS)

Marek, T.

2002-01-01

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

Light-emitting dendrimer film morphology: A neutron reflectivity study

Science.gov (United States)

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

2010-06-01

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

Molecular dynamics simulation of coarse-grained poly(L-lysine) dendrimers.

Science.gov (United States)

Rahimi, Ali; Amjad-Iranagh, Sepideh; Modarress, Hamid

2016-03-01

Poly(L-lysine) (PLL) dendrimer are amino acid based macromolecules and can be used as drug delivery agents. Their branched structure allows them to be functionalized by various groups to encapsulate drug agents into their structure. In this work, at first, an attempt was made on all-atom simulation of PLL dendrimer of different generations. Based on all-atom results, a course-grained model of this dendrimer was designed and its parameters were determined, to be used for simulation of three generations of PLL dendrimer, at two pHs. Similar to the all-atom, the coarse-grained results indicated that by increasing the generation, the dendrimer becomes more spherical. At pH 7, the dendrimer had larger size, whereas at pH 12, due to back folding of branching chains, they had the tendency to penetrate into the inner layers. The calculated radial probability and radial distribution functions confirm that at pH 7, the PLL dendrimer has more cavities and as a result it can encapsulate more water molecules into its inner structure. By calculating the moment of inertia and the aspect ratio, the formation of spherical structure for PLL dendrimer was confirmed.

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.

A dual-targeting nanocarrier based on poly(amidoamine) dendrimers conjugated with transferrin and tamoxifen for treating brain gliomas.

Science.gov (United States)

Li, Yan; He, Hai; Jia, Xinru; Lu, Wan-Liang; Lou, Jinning; Wei, Yen

2012-05-01

A pH-sensitive dual-targeting drug carrier (G4-DOX-PEG-Tf-TAM) was synthesized with transferrin (Tf) conjugated on the exterior and Tamoxifen (TAM) in the interior of the fourth generation PAMAM dendrimers for enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. It was found that, on average, 7 doxorubicine (DOX) molecules, over 30 PEG(1000) and PEG(2000) chains and one Tf group were bonded on the periphery of each G4 PAMAM dendrimer, while 29 TAM molecules were encapsulated into the interior of per dendrimer. The pH-triggered DOX release was 32% at pH 4.5 and 6% at pH 7.4, indicating a comparatively fast drug release at weak acidic condition and stable state of the carrier at physiological environment. The in vitro assay of the drug transport across the BBB model showed that G4-DOX-PEG-Tf-TAM exhibited higher BBB transportation ability with the transporting ratio of 6.06% in 3 h. The carrier was internalized into C6 glioma cells upon crossing the BBB model by the coactions of TfR-mediated endocytosis and the inhibition effect of TAM to the drug efflux transports. Moreover, it also displayed the in vitro accumulation of DOX in the avascular C6 glioma spheroids made the tumor volume effectively reduced. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

2010-06-03

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

Multiple signal amplified electrochemiluminescent immunoassay for brombuterol detection using gold nanoparticles and polyamidoamine dendrimers-silver nanoribbon

Energy Technology Data Exchange (ETDEWEB)

Dong, Tiantian; Hu, Liuyi; Zhao, Kang; Deng, Anping, E-mail: denganping@suda.edu.cn; Li, Jianguo, E-mail: lijgsd@suda.edu.cn

2016-11-16

Electrochemiluminescent (ECL) immunosensor with multiple signal amplification was designed based on gold nanoparticles (AuNPs), polyamidoamine dendrimers (PAMAM) and silver-cysteine hybrid nanoribbon (SNR). Low toxic L-cysteine capped CdSe QDs was chosen as the ECL signal probe. To verify the proposed ultrasensitive ECL immunosensor for β-adrenergic agonists (β-AA), we detected Brombuterol (Brom) as a proof-of-principle analyte. Therein, AuNPs as the substrate can simplify the experiment process, accelerate the electron transfer rate, and carry more coating antigen (Ag-OVA) to enlarge ECL signal. On one hand, SNR on the surface of electrode can avoid the aggregation of AuNPs, and SNR-PAMAM-AuNPs also can be acted as a good accelerator for electron transfer. On the other hand, PAMAM (16 -NH{sub 2}) functionalized SNR (SNR-PAMAM) with numerous amino groups could be employed to bond abundant actived QDs to further amplify ECL signal. The new immunosensor can offer a simple, reliable, rapid, and selective detection for Brom, which have a dynamic range of 0.005–700 ng mL{sup −1} with a low detection limit at 1.5 pg mL{sup −1}. The proposed biosensor will extend the application of nanomaterials in ECL immunoassays and open a new road for the detection of Brom and other β-AA in the future. - Highlights: • A multiple signal amplification ECL immunosensor of eco-friendly CdSe QDs for brombuterol determination was developed. • Besides substrates, AuNPs and PAMAM-SNR were creatively used to accelerate the electron transport between electrode and QDs. • SNR-PAMAM with numerous amino groups also could be employed to bond abundant actived QDs to amplify ECL signal. • Competitive immunoassay was performed with ECL to detect small molecules of brombuterol. • It provided a method for detecting Brom and enlarged the usage of QDs, AuNPs and SNR-PAMAM in ECL biosensing.

Multiple signal amplified electrochemiluminescent immunoassay for brombuterol detection using gold nanoparticles and polyamidoamine dendrimers-silver nanoribbon

International Nuclear Information System (INIS)

Dong, Tiantian; Hu, Liuyi; Zhao, Kang; Deng, Anping; Li, Jianguo

2016-01-01

Electrochemiluminescent (ECL) immunosensor with multiple signal amplification was designed based on gold nanoparticles (AuNPs), polyamidoamine dendrimers (PAMAM) and silver-cysteine hybrid nanoribbon (SNR). Low toxic L-cysteine capped CdSe QDs was chosen as the ECL signal probe. To verify the proposed ultrasensitive ECL immunosensor for β-adrenergic agonists (β-AA), we detected Brombuterol (Brom) as a proof-of-principle analyte. Therein, AuNPs as the substrate can simplify the experiment process, accelerate the electron transfer rate, and carry more coating antigen (Ag-OVA) to enlarge ECL signal. On one hand, SNR on the surface of electrode can avoid the aggregation of AuNPs, and SNR-PAMAM-AuNPs also can be acted as a good accelerator for electron transfer. On the other hand, PAMAM (16 -NH_2) functionalized SNR (SNR-PAMAM) with numerous amino groups could be employed to bond abundant actived QDs to further amplify ECL signal. The new immunosensor can offer a simple, reliable, rapid, and selective detection for Brom, which have a dynamic range of 0.005–700 ng mL"−"1 with a low detection limit at 1.5 pg mL"−"1. The proposed biosensor will extend the application of nanomaterials in ECL immunoassays and open a new road for the detection of Brom and other β-AA in the future. - Highlights: • A multiple signal amplification ECL immunosensor of eco-friendly CdSe QDs for brombuterol determination was developed. • Besides substrates, AuNPs and PAMAM-SNR were creatively used to accelerate the electron transport between electrode and QDs. • SNR-PAMAM with numerous amino groups also could be employed to bond abundant actived QDs to amplify ECL signal. • Competitive immunoassay was performed with ECL to detect small molecules of brombuterol. • It provided a method for detecting Brom and enlarged the usage of QDs, AuNPs and SNR-PAMAM in ECL biosensing.

Organic Light-Emitting Diodes Using Multifunctional Phosphorescent Dendrimers with Iridium-Complex Core and Charge-Transporting Dendrons

Science.gov (United States)

Tsuzuki, Toshimitsu; Shirasawa, Nobuhiko; Suzuki, Toshiyasu; Tokito, Shizuo

2005-06-01

We report a novel class of light-emitting materials for use in organic light-emitting diodes (OLEDs): multifunctional phosphorescent dendrimers that have a phosphorescent core and dendrons based on charge-transporting building blocks. We synthesized first-generation and second-generation dendrimers consisting of a fac-tris(2-phenylpyridine)iridium [Ir(ppy)3] core and hole-transporting phenylcarbazole-based dendrons. Smooth amorphous films of these dendrimers were formed by spin-coating them from solutions. The OLEDs using the dendrimer exhibited bright green or yellowish-green emission from the Ir(ppy)3 core. The OLEDs using the film containing a mixture of the dendrimer and an electron-transporting material exhibited higher efficiency than those using the neat dendrimer film. The external quantum efficiency of OLEDs using the film containing a mixture of the first-generation dendrimer and an electron-transporting material was as high as 7.6%.

Effect of deoxycholate conjugation on stability of pDNA/polyamidoamine-diethylentriamine (PAM-DET) polyplex against ionic strength.

Science.gov (United States)

Jeong, Yunseong; Jin, Geun-Woo; Choi, Eunjung; Jung, Ji Hyuk; Park, Jong-Sang

2011-11-28

Polyplexes formed from cationic polymer/pDNA have been known to be vulnerable to external ionic strength. To improve polyplex stability against ionic strength, we attempted the chemical conjugation of the hydrophobic deoxycholate (DC) moiety to the polyamidoamine-diethylenetriamine (PAM-DET) dendrimer. Dynamic light scattering studies showed that the tolerance of the resulting PAM-DET-DC against ionic strength is higher than that of PAM-DET. In addition, we confirmed that the stability of polyplex has a strong relationship with the degree of conjugation of the DC moiety to the PAM-DET dendrimer and the charge ratio of PAM-DET-DC. Furthermore, the transfection efficiency of the PAM-DET-DC polyplex is higher than that of PAM-DET but its cytotoxicity remains the same. Therefore, the chemical conjugation of DC is a safe and effective method for increasing the stability of supramolecules formed from electrostatic interaction. Copyright © 2011 Elsevier B.V. All rights reserved.

Enhanced A3 adenosine receptor selectivity of multivalent nucleoside-dendrimer conjugates

Directory of Open Access Journals (Sweden)

Shainberg Asher

2008-10-01

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

Amplified spontaneous emission and laser emission from a high optical-gain medium of dye-doped dendrimer

International Nuclear Information System (INIS)

Yokoyama, Shiyoshi; Nakahama, Tatsuo; Mashiko, Shinro

2005-01-01

We measured the amplified spontaneous emission and laser emission from high-gain media of laser-dye encapsulated dendrimers. A highly branched poly(amidoamine) (PAMAM-OH) dendrimer formed a guest-host complex with a conventional laser-dye (DCM), resulting in a high optical-gain. Of particular note was the appearance of a laser threshold, above which a super-narrowed laser spectrum was observed, although laser feedback was caused without any mirror cavity devices. The optical feedback was attributed to spatial confinement of the light due to gain guiding under optical excitation. The laser spectrum clearly indicated a resonant laser-mode with a spectrum linewidth of less than 0.1 nm. This order of spectrum narrowing is comparable to that seen in the laser emission from ordinary laser devices

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

Science.gov (United States)

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

2010-07-20

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

Physico-chemical studies on the interaction of dendrimers with lipid bilayers. 1. Effect of dendrimer generation and liposome surface charge.

Science.gov (United States)

Roy, Biplab; Panda, Amiya Kumar; Parimi, Srinivas; Ametov, Igor; Barnes, Timothy; Prestidge, Clive A

2014-01-01

Studies on the interaction of different generation poly (amido amine) (PAMAM) dendrimers (2G, 4G and 6G) and liposomes of different compositions were carried out by a combined turbidity, dynamic light scattering and atomic force microscopic measurements. Liposomes comprising soy lecithin (SLC, negative surface charge), 1, 2-palmitoyl-sn-glycero-3-phosphatidylcholine (DPPC, mildly positive surface charge), 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol (DPPG, negatively charged) and a biologically simulated mixture of DPPC + DPPG (7:3, M/M, negatively charged) were used as model bilayers. 30 wt% cholesterol was used in each combination as it is known to control the fluidity of membrane bilayers. Silica was used as a negatively charged hard sphere model with an aim to compare the results. Both the turbidity and hydrodynamic diameter values of all the liposomes, except DPPC, passed through maxima upon the progressive addition of PAMAM; the effect was insignificant in case of DPPC. Formation of dendriosome, a complex formed between dendrimer and liposome, resulted in the charge reversal of the negatively charged liposomes. Interaction between PAMAM and liposome was found to be governed by electrostatic as well as hydrogen bonding. Generation dependent PAMAM activity followed the order: 6G >4G>2G in terms of overall dendrimer concentration. However, interestingly, the order was reverse when PAMAM activity was considered in terms of total end group concentrations. AFM studies reveal the rupture of bilayer structure upon addition of dendrimer.

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

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. Copyright © 2013 Elsevier B.V. All rights reserved.

Charge transport properties of carbazole dendrimers in organic field-effect transistors

Science.gov (United States)

Mutkins, Karyn; Chen, Simon S. Y.; Aljada, Muhsen; Powell, Ben J.; Olsen, Seth; Burn, Paul L.; Meredith, Paul

2011-10-01

We report three generations of p-type dendrimer semiconductors comprised of spirobifluorene cores, carbazole branching units and fluorene surface groups for use in organic field-effect transistors (OFETs). The group of dendrimers are defined by their generation and noted as SBF-(Gx)2, where x is the generation. Top contact-bottom gate OFETs were fabricated by spin-coating the dendrimers onto an n-octyltrichlorosilane (OTS) passivated silicon dioxide surface. The dendrimer films were found to be amorphous. The highest mobility was measured for the first generation dendrimer (SBF-(G1)2), which had an average mobility of (6.6 +/- 0.2) × 10-5 cm2/V s and an ON/OFF ratio of 3.0 × 104. As the generation of the dendrimer was increased there was only a slight decrease in the measured mobility in spite of the significantly different molecular sizes of the dendrimers. The mobility of SBF-(G3)2, which had a hydrodynamic radius almost twice of SBF-(G1)2, still had an average mobility of (4.7 +/- 0.6) × 10-5 cm2/V s and an ON/OFF ratio of 2.7 × 103. Density functional theory calculations showed that the highest occupied molecular orbital was distributed over the core and carbazole units meaning that both intra- and intermolecular charge transfer could occur enabling the hole mobility to remain essentially constant even though the dendrimers would pack differently in the solid-state.

Tailoring the dendrimer core for efficient gene delivery.

Science.gov (United States)

Hu, Jingjing; Hu, Ke; Cheng, Yiyun

2016-04-15

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

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

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.

Dendrimer brain uptake and targeted therapy for brain injury in a large animal model of hypothermic circulatory arrest.

Science.gov (United States)

Mishra, Manoj K; Beaty, Claude A; Lesniak, Wojciech G; Kambhampati, Siva P; Zhang, Fan; Wilson, Mary A; Blue, Mary E; Troncoso, Juan C; Kannan, Sujatha; Johnston, Michael V; Baumgartner, William A; Kannan, Rangaramanujam M

2014-03-25

Treatment of brain injury following circulatory arrest is a challenging health issue with no viable therapeutic options. Based on studies in a clinically relevant large animal (canine) model of hypothermic circulatory arrest (HCA)-induced brain injury, neuroinflammation and excitotoxicity have been identified as key players in mediating the brain injury after HCA. Therapy with large doses of valproic acid (VPA) showed some neuroprotection but was associated with adverse side effects. For the first time in a large animal model, we explored whether systemically administered polyamidoamine (PAMAM) dendrimers could be effective in reaching target cells in the brain and deliver therapeutics. We showed that, upon systemic administration, hydroxyl-terminated PAMAM dendrimers are taken up in the brain of injured animals and selectively localize in the injured neurons and microglia in the brain. The biodistribution in other major organs was similar to that seen in small animal models. We studied systemic dendrimer-drug combination therapy with two clinically approved drugs, N-acetyl cysteine (NAC) (attenuating neuroinflammation) and valproic acid (attenuating excitotoxicity), building on positive outcomes in a rabbit model of perinatal brain injury. We prepared and characterized dendrimer-NAC (D-NAC) and dendrimer-VPA (D-VPA) conjugates in multigram quantities. A glutathione-sensitive linker to enable for fast intracellular release. In preliminary efficacy studies, combination therapy with D-NAC and D-VPA showed promise in this large animal model, producing 24 h neurological deficit score improvements comparable to high dose combination therapy with VPA and NAC, or free VPA, but at one-tenth the dose, while significantly reducing the adverse side effects. Since adverse side effects of drugs are exaggerated in HCA, the reduced side effects with dendrimer conjugates and suggestions of neuroprotection offer promise for these nanoscale drug delivery systems.

Magnetic solid-phase extraction of non-steroidal anti-inflammatory drugs from environmental water samples using polyamidoamine dendrimer functionalized with magnetite nanoparticles as a sorbent.

Science.gov (United States)

Alinezhad, Heshmatollah; Amiri, Amirhassan; Tarahomi, Mehrasa; Maleki, Behrooz

2018-06-01

A novel polyamidoamine dendrimer functionalized with Fe 3 O 4 nanoparticles (Fe 3 O 4 @PAMAM) had been fabricated and used as magnetic solid-phase extraction (MSPE) adsorbent. The Fe 3 O 4 @PAMAM nanocomposites were characterized by X-ray powder diffraction, Fourier transform infrared spectroscopy, field-emission scanning electron spectroscopy, elemental analytical, and thermal gravimetric analysis. The MSPE method coupled with high-performance liquid chromatography with an ultraviolet detection system was applied for the separation/analysis of non-steroidal anti-inflammatory drugs (NSAIDs). Major parameters affecting the extraction efficiency of the selected drugs were optimized. Under optimal conditions, the enrichment factors for the proposed method were 701835. The linear range, limit of detection, correlation coefficient (r), and relative standard deviation (RSD) were found to be 0.15-500 ng mL -1 , 0.050.08 ng mL -1 , 0.99320.9967, and 4.5-7.0% (n = 5, 0.2, 10 and 300 ng mL -1 ), respectively. The method was successfully applied to the determination of NSAIDs in the real water samples. The recoveries of spiked water samples were in the range of 93.6-98.9% with RSDs varying from 6.1% to 9.0%, showing the good accuracy of the method. Copyright © 2018 Elsevier B.V. All rights reserved.

In Vitro/In Vivo Evaluation of Dexamethasone--PAMAM Dendrimer Complexes for Retinal Drug Delivery.

Science.gov (United States)

Yavuz, Burçin; Pehlivan, Sibel Bozdağ; Vural, İmran; Ünlü, Nurşen

2015-11-01

Current treatment options for diabetic retinopathy (DR) have side effects because of invasive application and topical application does not generally result in therapeutic levels in the target tissue. Therefore, improving the drug delivery to retina, following topical administration, might be a solution to DR treatment problems. The purpose of this study was to investigate the complexation effects of poly(amidoamine) (PAMAM) dendrimers on ocular absorption of dexamethasone (DEX). Using different PAMAM generations, complex formulations were prepared and characterized. Formulations were evaluated in terms of cytotoxicity and cell permeability, as well as ex vivo transport across ocular tissues. The ocular pharmacokinetic properties of DEX formulations were studied in Sprague-Dawley rats following topical and subconjunctival applications, to evaluate the effect of PAMAM on retinal delivery of DEX. Methyl-thiazol-tetrazolium (MTT) assay indicated that all groups resulted in cell viability comparable to DEX solution (87.5%), with the cell viability being the lowest for G3 complex at 73.5%. Transport study results showed that dendrimer complexation increases DEX transport across both cornea and sclera tissues. The results of in vivo studies were also indicated that especially anionic DEX-PAMAM complex formulations have reached higher DEX concentrations in ocular tissues compared with plain DEX suspension. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Some new aspects of dendrimer applications

International Nuclear Information System (INIS)

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

2005-01-01

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

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

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

International Nuclear Information System (INIS)

Uzun, K.; Cevik, E.; Senel, M.; Soezeri, H.; Baykal, A.; Abasiyanik, M. F.; Toprak, M. S.

2010-01-01

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

Poly-(amidoamine) dendrimers with a precisely core positioned sulforhodamine B molecule for comparative biological tracing and profiling

DEFF Research Database (Denmark)

Wu, Lin-Ping; Ficker, Mario; Mejlsøe, Søren Leth

2017-01-01

of the fluorophore was not affected by pH and temperature. Since the stoichiometry of the fluorophore to the dendrimer is 1:1, we were able to directly compare uptake kinetics, the mode of uptake, trafficking and safety of dendrimers of different end-terminal functionality (carboxylated vs. pyrrolidonated) by two...... phenotypically different human endothelial cell types (the human brain capillary endothelial cell line hCMEC/D3 and human umbilical vein endothelial cells), and without interference of the fluorophore in uptake processes. The results demonstrate comparable uptake kinetics and a predominantly clathrin...

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.

PAMAM dendrimer hydrogel film—biocompatible material to an efficient dermal delivery of drugs

Science.gov (United States)

Magalhães, Thamiris Machado; Guerra, Rodrigo Cinti; San Gil, Rosane Aguiar da Silva; Valente, Ana Paula; Simão, Renata Antoun; Soares, Bluma Guenther; Mendes, Thamara de Carvalho; Pyrrho, Alexandre dos Santos; Sousa, Valeria Pereira de; Rodrigues-Furtado, Vanessa Lúcia

2017-08-01

We report the preparation, characterization, and drug release kinetics of a pH-responsive hydrogel film from a dendrimer megamer. The megamer (GP32) is a three-dimensional reticulated structure with a mean diameter of 71.16 nm (PDI 0.150) and was prepared by the reaction between Poly(amidoamine) generation4 (PAMAM G4) dendrimer and glutaraldehyde (G:P molar ratio 32). The crosslinking units in the megamer are provided mainly by the bicyclic dimer 2-hydroxy-3,4,4a,7,8,8a-hexahydro-2 H-chromene-6-carbaldehyde as determined by high-resolution (800 MHz) 1H NMR and FTIR. The hydrogel film (F[GP32]) is formed upon evaporation of a methanolic solution of the megamer and has a high degree of organization and homogeneity. Further crosslinking with glutaraldehyde (CLF[GP32]) enhanced the mechanical properties of the hydrogel film. The chemical constitution and unique megamer architecture enable the hydrogel film to carry both lipophilic and hydrophilic substances. The film did not cause any dermal irritation or clinical signs of toxicity in tests on rabbits, allowed for a sustained release of ketoprofen and played an important role in the process of drug delivery into the receptor medium. This performance taken together with the absence of toxicity makes this hydrogel film a good choice for dermal sustained drug release. [Figure not available: see fulltext.

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

, characterized by the heterogeneous ET rate constant of 7.1 0.1 s1; they can be used for electronic wiring of glucose-oxidizing FAD-containing enzymes, such as hexose oxidase (HOX), and further bioelectrocatalysis of glucose oxidation, starting, at pH 7, from -100 mV vs. Ag/AgCl. Thus, dendrimer...

pH responsiveness of dendrimer-like poly(ethylene oxide)s.

Science.gov (United States)

Feng, Xiaoshuang; Taton, Daniel; Borsali, Redouane; Chaikof, Elliot L; Gnanou, Yves

2006-09-06

Poly(ethylene oxide) (PEO) and poly(acrylic acid) (PAA), two polymers known to form pH-sensitive aggregates through noncovalent interactions, were assembled in purposely designed architecture -a dendrimer-like PEO scaffold carrying short inner PAA chains-to produce unimolecular systems that exhibit pH responsiveness. Because of the particular placement of the PAA chains within the dendrimer-like structure, intermolecular complexation between acrylic acid (AA) and ethylene oxide (EO) units-and thus macroscopic aggregation or even mesoscopic micellization-could be avoided in favor of the sole intramolecular complexation. The sensitivity of such interactions to pH was exploited to generate dendrimer-like PEOs that reversibly shrink and expand with the pH. Such PAA-carrying dendrimer-like PEOs were synthesized in two main steps. First, a fifth-generation dendrimer-like PEO was obtained by combining anionic ring-opening polymerization (AROP) of ethylene oxide from a tris-hydroxylated core and selective branching reactions of PEO chain ends. To this end, an AB(2)C-type branching agent was designed: the latter includes a chloromethyl (A) group for its covalent attachment to the arm ends, two geminal hydroxyls (B(2)) protected in the form of a ketal ring for the growth of subsequent PEO generations by AROP, and a vinylic (C) double bonds for further functionalization of the interior of dendrimer-like PEOs. Reiteration of AROP and derivatization of PEO branches allowed us to prepare a dendrimer-like PEO of fourth generation with a total molar mass of 52,000 g x mol(-1), containing 24 external hydroxyl functions and 21 inner vinylic groups in the interior. A fifth generation of PEO chains was generated from this parent dendrimer-like PEO of fourth generation using a "conventional" AB(2)-type branching agent, and 48 PEO branches could be grown by AROP. The 48 outer hydroxy-end groups of the fifth-generation dendrimer-like PEO obtained were subsequently quantitatively

Water dispersal and functionalization of hydrophobic Iron oxide nanoparticles with lipid-modified poly(amidoamine) dendrimers

NARCIS (Netherlands)

Boni, A; Albertazzi, L.; Innocenti, C; Gemmi, M; Bifone, A

2013-01-01

A novel and facile method for water dispersal of hydrophobic iron oxide nanoparticles based on the amphiphilic PAMAM-C-12 dendrimer is described. Stable and highly concentrated water dispersions of multifunctional, magnetic nanoparticles were obtained with this single-step approach, and showed

Activated Microglia Targeting Dendrimer-Minocycline Conjugate as Therapeutics for Neuroinflammation.

Science.gov (United States)

Sharma, Rishi; Kim, Soo-Young; Sharma, Anjali; Zhang, Zhi; Kambhampati, Siva Pramodh; Kannan, Sujatha; Kannan, Rangaramanujam M

2017-11-15

Brain-related disorders have outmatched cancer and cardiovascular diseases worldwide as the leading cause of morbidity and mortality. The lack of effective therapies and the relatively dry central nervous system (CNS) drug pipeline pose formidable challenge. Superior, targeted delivery of current clinically approved drugs may offer significant potential. Minocycline has shown promise for the treatment of neurological diseases owing to its ability to penetrate the blood-brain barrier (BBB) and potency. Despite its potential in the clinic and in preclinical models, the high doses needed to affect a positive therapeutic response have led to side effects. Targeted delivery of minocycline to the injured site and injured cells in the brain can be highly beneficial. Systemically administered hydroxyl poly(amidoamine) (PAMAM) generation-6 (G6) dendrimers have a longer blood circulation time and have been shown to cross the impaired BBB. We have successfully prepared and characterized the in vitro efficacy and in vivo targeting ability of hydroxyl-G6 PAMAM dendrimer-9-amino-minocycline conjugate (D-mino). Minocycline is a challenging drug to carry out chemical transformations due to its inherent instability. We used a combination of a highly efficient and mild copper catalyzed azide-alkyne click reaction (CuAAC) along with microwave energy to conjugate 9-amino-minocycline (mino) to the dendrimer surface via enzyme responsive linkages. D-mino was further evaluated for anti-inflammatory and antioxidant activity in lipopolysaccharides-activated murine microglial cells. D-mino conjugates enhanced the intracellular availability of the drug due to their rapid uptake, suppressed inflammatory cytokine tumor necrosis factor α (TNF-α) production, and reduced oxidative stress by suppressing nitric oxide production, all significantly better than the free drug. Fluorescently labeled dendrimer conjugate (Cy5-D-mino) was systematically administered (intravenous, 55 mg/kg) on postnatal

Dendrimer Brain Uptake and Targeted Therapy for Brain Injury in a Large Animal Model of Hypothermic Circulatory Arrest

Science.gov (United States)

2015-01-01

Treatment of brain injury following circulatory arrest is a challenging health issue with no viable therapeutic options. Based on studies in a clinically relevant large animal (canine) model of hypothermic circulatory arrest (HCA)-induced brain injury, neuroinflammation and excitotoxicity have been identified as key players in mediating the brain injury after HCA. Therapy with large doses of valproic acid (VPA) showed some neuroprotection but was associated with adverse side effects. For the first time in a large animal model, we explored whether systemically administered polyamidoamine (PAMAM) dendrimers could be effective in reaching target cells in the brain and deliver therapeutics. We showed that, upon systemic administration, hydroxyl-terminated PAMAM dendrimers are taken up in the brain of injured animals and selectively localize in the injured neurons and microglia in the brain. The biodistribution in other major organs was similar to that seen in small animal models. We studied systemic dendrimer–drug combination therapy with two clinically approved drugs, N-acetyl cysteine (NAC) (attenuating neuroinflammation) and valproic acid (attenuating excitotoxicity), building on positive outcomes in a rabbit model of perinatal brain injury. We prepared and characterized dendrimer-NAC (D-NAC) and dendrimer-VPA (D-VPA) conjugates in multigram quantities. A glutathione-sensitive linker to enable for fast intracellular release. In preliminary efficacy studies, combination therapy with D-NAC and D-VPA showed promise in this large animal model, producing 24 h neurological deficit score improvements comparable to high dose combination therapy with VPA and NAC, or free VPA, but at one-tenth the dose, while significantly reducing the adverse side effects. Since adverse side effects of drugs are exaggerated in HCA, the reduced side effects with dendrimer conjugates and suggestions of neuroprotection offer promise for these nanoscale drug delivery systems. PMID:24499315

Computer simulations of dendrimer-polyelectrolyte complexes.

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Pandav, Gunja; Ganesan, Venkat

2014-08-28

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

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

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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

Dendrimer ligands-capped CH3NH3PbBr3 perovskite nanocrystals with delayed halide exchange and record stability against both moisture and water

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Xu, Yiren; Xu, Shuhong; Shao, Haibao; Jiang, Han; Cui, Yiping; Wang, Chunlei

2018-06-01

CH3NH3PbBr3 perovskite nanocrystals (NCs) suffer from poor stability because of their high sensitivity to environmental moisture and water. To solve this problem, previous works mainly focus on embedding perovskite NCs into water-resistant matrix to form large composites (size of microns or larger). As an alternative solution without serious changing of NC size, enhancing the stability of perovskite NCs themselves by ligand engineering is rarely reported. In this work, we used hyperbranched polyamidoamine (PAMAM) dendrimers with two different generations (G0 and G4) to synthesize CH3NH3PbBr3 perovskite NCs with high photoluminescence (PL) quantum yields (QY) above 70% and a new record stability. A novel dendrimers generation-dependent stability of perovskite NCs was observed. The water-resistance time is 18 h (27 h) for perovskite NCs capped by G0 (G4) generation of PAMAM, which is 7 times (11 times) longer than that of traditional oleic acid-capped NCs. Similar PAMAM generation-related stability is also observed in moisture-resistance tests. The stability time against moisture is 500 h (800 h) for G0 (G4) generation of PAMAM-capped perovskite NCs, which is a new record stability time against moisture for CH3NH3PbBr3 perovskite NCs. In addition, our results also indicate that PAMAM ligands outside perovskite NCs can dramatically slow down the speed of halide exchange. Even for the mixture of perovskite NCs with two different halide composition, the original luminescence properties of PAMAM-capped perovskite NCs can retain after mixing. In view of slow halide exchange speed, excellent water and moisture stability, PAMAM dendrimers-capped perovskite NCs and their mixture are available as color conversion single layer in fabrication of light-emitting diodes (LED).

Dendrimer ligands-capped CH3NH3PbBr3 perovskite nanocrystals with delayed halide exchange and record stability against both moisture and water.

Science.gov (United States)

Xu, Yiren; Xu, Shuhong; Shao, Haibao; Jiang, Han; Cui, Yiping; Wang, Chunlei

2018-06-08

CH 3 NH 3 PbBr 3 perovskite nanocrystals (NCs) suffer from poor stability because of their high sensitivity to environmental moisture and water. To solve this problem, previous works mainly focus on embedding perovskite NCs into water-resistant matrix to form large composites (size of microns or larger). As an alternative solution without serious changing of NC size, enhancing the stability of perovskite NCs themselves by ligand engineering is rarely reported. In this work, we used hyperbranched polyamidoamine (PAMAM) dendrimers with two different generations (G0 and G4) to synthesize CH 3 NH 3 PbBr 3 perovskite NCs with high photoluminescence (PL) quantum yields (QY) above 70% and a new record stability. A novel dendrimers generation-dependent stability of perovskite NCs was observed. The water-resistance time is 18 h (27 h) for perovskite NCs capped by G0 (G4) generation of PAMAM, which is 7 times (11 times) longer than that of traditional oleic acid-capped NCs. Similar PAMAM generation-related stability is also observed in moisture-resistance tests. The stability time against moisture is 500 h (800 h) for G0 (G4) generation of PAMAM-capped perovskite NCs, which is a new record stability time against moisture for CH 3 NH 3 PbBr 3 perovskite NCs. In addition, our results also indicate that PAMAM ligands outside perovskite NCs can dramatically slow down the speed of halide exchange. Even for the mixture of perovskite NCs with two different halide composition, the original luminescence properties of PAMAM-capped perovskite NCs can retain after mixing. In view of slow halide exchange speed, excellent water and moisture stability, PAMAM dendrimers-capped perovskite NCs and their mixture are available as color conversion single layer in fabrication of light-emitting diodes (LED).

Effective transvascular delivery of nanoparticles across the blood-brain tumor barrier into malignant glioma cells

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Sharma Kamal

2008-12-01

Full Text Available Abstract Background Effective transvascular delivery of nanoparticle-based chemotherapeutics across the blood-brain tumor barrier of malignant gliomas remains a challenge. This is due to our limited understanding of nanoparticle properties in relation to the physiologic size of pores within the blood-brain tumor barrier. Polyamidoamine dendrimers are particularly small multigenerational nanoparticles with uniform sizes within each generation. Dendrimer sizes increase by only 1 to 2 nm with each successive generation. Using functionalized polyamidoamine dendrimer generations 1 through 8, we investigated how nanoparticle size influences particle accumulation within malignant glioma cells. Methods Magnetic resonance and fluorescence imaging probes were conjugated to the dendrimer terminal amines. Functionalized dendrimers were administered intravenously to rodents with orthotopically grown malignant gliomas. Transvascular transport and accumulation of the nanoparticles in brain tumor tissue was measured in vivo with dynamic contrast-enhanced magnetic resonance imaging. Localization of the nanoparticles within glioma cells was confirmed ex vivo with fluorescence imaging. Results We found that the intravenously administered functionalized dendrimers less than approximately 11.7 to 11.9 nm in diameter were able to traverse pores of the blood-brain tumor barrier of RG-2 malignant gliomas, while larger ones could not. Of the permeable functionalized dendrimer generations, those that possessed long blood half-lives could accumulate within glioma cells. Conclusion The therapeutically relevant upper limit of blood-brain tumor barrier pore size is approximately 11.7 to 11.9 nm. Therefore, effective transvascular drug delivery into malignant glioma cells can be accomplished by using nanoparticles that are smaller than 11.7 to 11.9 nm in diameter and possess long blood half-lives.

Substrate-Triggered Exosite Binding: Synergistic Dendrimer/Folic Acid Action for Achieving Specific, Tight-Binding to Folate Binding Protein.

Science.gov (United States)

Chen, Junjie; van Dongen, Mallory A; Merzel, Rachel L; Dougherty, Casey A; Orr, Bradford G; Kanduluru, Ananda Kumar; Low, Philip S; Marsh, E Neil G; Banaszak Holl, Mark M

2016-03-14

Polymer-ligand conjugates are designed to bind proteins for applications as drugs, imaging agents, and transport scaffolds. In this work, we demonstrate a folic acid (FA)-triggered exosite binding of a generation five poly(amidoamine) (G5 PAMAM) dendrimer scaffold to bovine folate binding protein (bFBP). The protein exosite is a secondary binding site on the protein surface, separate from the FA binding pocket, to which the dendrimer binds. Exosite binding is required to achieve the greatly enhanced binding constants and protein structural change observed in this study. The G5Ac-COG-FA1.0 conjugate bound tightly to bFBP, was not displaced by a 28-fold excess of FA, and quenched roughly 80% of the initial fluorescence. Two-step binding kinetics were measured using the intrinsic fluorescence of the FBP tryptophan residues to give a KD in the low nanomolar range for formation of the initial G5Ac-COG-FA1.0/FBP* complex, and a slow conversion to the tight complex formed between the dendrimer and the FBP exosite. The extent of quenching was sensitive to the choice of FA-dendrimer linker chemistry. Direct amide conjugation of FA to G5-PAMAM resulted in roughly 50% fluorescence quenching of the FBP. The G5Ac-COG-FA, which has a longer linker containing a 1,2,3-triazole ring, exhibited an ∼80% fluorescence quenching. The binding of the G5Ac-COG-FA1.0 conjugate was compared to poly(ethylene glycol) (PEG) conjugates of FA (PEGn-FA). PEG2k-FA had a binding strength similar to that of FA, whereas other PEG conjugates with higher molecular weight showed weaker binding. However, no PEG conjugates gave an increased degree of total fluorescence quenching.

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

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

2013-09-03

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

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.

Functionalized Poly(propylene imine) Dendrimers as Novel Phase Transfer Catalyst in Supercritical Cabon Dioxide

NARCIS (Netherlands)

Goetheer, E.L.V.; Baars, M.W.P.L.; Broeke, van den L.J.P.; Meijer, E.W.; Keurentjes, J.T.F.

2000-01-01

Perfluoro-functionalized poly(propylene imine) dendrimers have been used as reactive extractants for anionic species and as phase transfer catalysts for two types of reactions. Different generations of dendrimers have been used for applications in carbon dioxide. First, the reactive extraction of

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

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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

Molecular dynamics simulations of single siloxane dendrimers: Molecular structure and intramolecular mobility of terminal groups

Science.gov (United States)

Kurbatov, A. O.; Balabaev, N. K.; Mazo, M. A.; Kramarenko, E. Yu.

2018-01-01

Molecular dynamics simulations of two types of isolated siloxane dendrimers of various generations (from the 2nd to the 8th) have been performed for temperatures ranging from 150 K to 600 K. The first type of dendrimer molecules has short spacers consisting of a single oxygen atom. In the dendrimers of the second type, spacers are longer and comprised of two oxygen atoms separated by a single silicon atom. A comparative analysis of molecular macroscopic parameters such as the gyration radius and the shape factor as well as atom distributions within dendrimer interior has been performed for varying generation number, temperature, and spacer length. It has been found that the short-spacer dendrimers of the 7th and 8th generations have a stressed central part with elongated bonds and deformed valence angles. Investigation of the time evolution of radial displacements of the terminal Si atoms has shown that a fraction of the Si groups have a reduced mobility. Therefore, rather long time trajectories (of the order of tens of nanoseconds) are required to study dendrimer intramolecular dynamics.

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

International Nuclear Information System (INIS)

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

2013-01-01

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

Vibrational spectroscopic study of cationic phosphorus dendrimers with aminoethylpiperidine terminal groups

Science.gov (United States)

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

2018-04-01

Two generations of phosphoric dendrimers with piperidine functional groups were synthesized for use in biology and medicine. Neutral samples are soluble in organic solvents but after protonation these dendrimers become water soluble and can be used for biological experiments. The FTIR and FT Raman spectra of two generations of dendrimers Gi constructed from the cyclotriphosphazene core, repeating units sbnd Osbnd C6H4sbnd CHdbnd Nsbnd N(CH3)sbnd P(S)molecular structure and vibrational spectra of the first generation dendrimer was performed by the method of DFT. This molecule has flat, repeating units and a plane of symmetry passing through the core. The calculation of the distribution of potential energy made it possible to classify the bands in the experimental spectra of dendrimers. Amine groups are manifested in the form of a band of NH stretching vibrations at 3389 cm-1 in the IR spectrum of G1. NH+ stretching bands located at 2646 and 2540 cm-1 in the IR spectrum of G2. The stretching vibrations of NH+ groups are noticeably shifted to low frequencies due to the formation of a hydrogen bond with the chlorine atom. The line at 1575 cm-1 in the Raman spectrum of G1 is characteristic for repeating units.

Mean first passage time for random walk on dual structure of dendrimer

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Li, Ling; Guan, Jihong; Zhou, Shuigeng

2014-12-01

The random walk approach has recently been widely employed to study the relations between the underlying structure and dynamic of complex systems. The mean first-passage time (MFPT) for random walks is a key index to evaluate the transport efficiency in a given system. In this paper we study analytically the MFPT in a dual structure of dendrimer network, Husimi cactus, which has different application background and different structure (contains loops) from dendrimer. By making use of the iterative construction, we explicitly determine both the partial mean first-passage time (PMFT, the average of MFPTs to a given target) and the global mean first-passage time (GMFT, the average of MFPTs over all couples of nodes) on Husimi cactus. The obtained closed-form results show that PMFPT and EMFPT follow different scaling with the network order, suggesting that the target location has essential influence on the transport efficiency. Finally, the impact that loop structure could bring is analyzed and discussed.

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.

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-12-02

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

The Synthesis of N-Acetyllactosamine Functionalized Dendrimers, and the Functionalization of Silica Surfaces Using Tunable Dendrons and beta-Cyclodextrins

Science.gov (United States)

Ennist, Jessica Helen

Galectin-3 is beta-galactoside binding protein which is found in many healthy cells. In cancer, the galectin-3/tumor-associated Thomsen-Friedenreich antigen (TF antigen) interaction has been implicated in heterotypic and homotypic cellular adhesion and apoptotic signaling pathways. However, a stronger mechanistic understanding of the role of galectin-3 in these processes is needed. N-acetyllactosamine (LacNAc) is a non-native ligand for galectin-3 which binds with comparable affinity to the TF antigen and therefore an important ligand to study galectin-3 mediated processes. To study galectin-3 mediated homotypic cellular aggregation, four generations of polyamidoamine (PAMAM) dendrimers were functionalized with N-acetyllactosamine using a four-step chemoenzymatic route. The enzymatic step controlled the regiochemistry of the galactose addition to N-acetylglucosamine functionalized dendrimers using a recombinant beta-1,4-Galactosyltransferase-/UDP-4'-Gal Epimerase Fusion Protein (lgtB-galE). Homotypic cellular aggregation, which is promoted by the presence of galectin-3 as it binds to glycosides at the cell surface, was studied using HT-1080 fibrosarcoma, A549 lung, and DU-145 prostate cancer cell lines. In the presence of small LacNAc functionalized PAMAM dendrimers, galectin-3 induced cancer cellular aggregation was inhibited. However, the larger glycodendrimers induced homotypic cellular aggregation. Additionally, novel poly(aryl ether) dendronized silica surfaces designed for reversible adsorbtion of targeted analytes were synthesized, and characterization using X-ray Photoelectron Spectroscopy (XPS) was performed. Using a Cu(I) mediated cycloaddition "click" reaction, beta-cyclodextrin was appended to dendronized surfaces via triazole formation and also to a non-dendronized surface for comparison purposes. First generation G(1) dendrons have more than 6 times greater capacity to adsorb targeted analytes than slides functionalized with monomeric beta

Toxicity of PAMAM dendrimers to Chlamydomonas reinhardtii

International Nuclear Information System (INIS)

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

2010-01-01

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

Wetting and layering transitions in a nano-dendrimer PAMAM structure: Monte Carlo study

Science.gov (United States)

Aouini, S.; Ziti, S.; Labrim, H.; Bahmad, L.

2016-10-01

This study is based on a nano-model of the dendrimer polyamidoamine (PAMAM). The idea is to examine the magnetic properties of such models in the context of wetting and the layering transitions. The studied system consists of spins σ ={1/2} Ising ferromagnetic in real nanostructure found in different scientific domains. To study this system, we perform Monte Carlo simulations leading to interesting results recapitulated in two classes. The former is the ground state phase diagrams study. The latter is the magnetic properties at non null temperatures. Also, we analyzed the effect of the terms present in the Hamiltonian governing our system such as the external magnetic field and the exchange couplings interactions.

Water soluble cationic dextran derivatives containing poly(amidoamine) dendrons for efficient gene delivery.

Science.gov (United States)

Mai, Kaijin; Zhang, Shanshan; Liang, Bing; Gao, Cong; Du, Wenjun; Zhang, Li-Ming

2015-06-05

To develop new dextran derivatives for efficient gene delivery, the conjugation of poly(amidoamine) dendrons onto biocompatible dextran was carried out by a Cu(I)-catalyzed azide-alkyne cycloaddition, as confirmed by FTIR and (1)H NMR analyses. For resultant dextran conjugates with various generations of poly(amidoamine) dendrons, their buffering capacity and in vitro cytotoxicity were evaluated by acid-base titration and MTT tests, respectively. In particular, their physicochemical characteristics for the complexation with plasmid DNA were investigated by the combined analyses from agarose gel electrophoresis, zeta potential, particle size, transmission electron microscopy and fluorescence emission spectra. Moreover, their complexes with plasmid DNA were studied with respect to their transfection efficiency in human embryonic kidney (HEK293) cell lines. In the case of a higher generation of poly(amidoamine) dendrons, such a dextran conjugate was found to have much lower cytotoxicity and better gene delivery capability when compared to branched polyethylenimine (bPEI, 25kDa), a commonly used gene vector. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Dendrimer-based biosensor for chemiluminescent detection of DNA hybridization

International Nuclear Information System (INIS)

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

2011-01-01

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

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.

Preliminary biological evaluation of a urea-functionalized dendrimer

International Nuclear Information System (INIS)

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

2002-01-01

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

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

Dendrimer-protein interactions versus dendrimer-based nanomedicine.

Science.gov (United States)

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

2017-04-01

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

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

International Nuclear Information System (INIS)

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

2013-01-01

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

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.

Interaction of Dendritic Polymers with Synthetic Lipid and Cell Membranes

Science.gov (United States)

Mecke, Almut; Hong, Seungpyo; Bielinska, Anna U.; Banaszak Holl, Mark M.; Orr, Bradford G.; Baker, James R., Jr.

2004-03-01

Polyamidoamine (PAMAM) dendrimers are promising candidates for the development of nanoscale therapeutic transport agents. Here we present studies on dendrimer-membrane interactions leading to a better understanding of possible uptake mechanisms into cells. Using synthetic lipid and natural cell membranes as model systems it is shown that the effect of PAMAM dendrimers on a membrane strongly depends on the dendrimer generation, architecture and chemical properties of the branch end groups. Atomic force microscopy data indicates that generation 7 dendrimers have the ability to form small ( 10-100 nm) holes in a lipid bilayer. When dendrimers with otherwise identical chemical properties are arranged in a covalently linked cluster, no hole formation occurs. Dendrimer-lipid micelle formation is proposed and investigated as a possible mechanism for this behavior. Smaller dendrimers (generation 5) have a greatly reduced ability to remove lipid molecules from a bilayer. In addition to the size of the dendrimer, the charge of the branch end groups plays a significant role for dendrimer-membrane interactions. These results agree well with biological studies using cultured cells and point to a new mechanism of specific targeting and uptake into cells.

Toxicity of PAMAM dendrimers to Chlamydomonas reinhardtii

Energy Technology Data Exchange (ETDEWEB)

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

2010-10-15

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

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

Science.gov (United States)

Qamhieh, K.; Al-Shawwa, J.

2017-06-01

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

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

Science.gov (United States)

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

2014-04-01

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

Charge transport in highly efficient iridium cored electrophosphorescent dendrimers

Science.gov (United States)

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

2004-01-01

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

An intrinsically fluorescent dendrimer as a nanoprobe of cell transport.

Science.gov (United States)

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

2006-07-01

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

Dendrimer-Stabilized Gold Nanostars as a Multifunctional Theranostic Nanoplatform for CT Imaging, Photothermal Therapy, and Gene Silencing of Tumors.

Science.gov (United States)

Wei, Ping; Chen, Jingwen; Hu, Yong; Li, Xin; Wang, Han; Shen, Mingwu; Shi, Xiangyang

2016-12-01

Development of versatile nanomaterials combining diagnostic and therapeutic functionalities within one single nanoplatform is extremely important for tumor theranostics. In this work, the authors report the synthesis of a gold nanostar (Au NS)-based theranostic platform stabilized with cyclic arginine-glycine-aspartic (Arg-Gly-Asp, RGD) peptide-modified amine-terminated generation 3 poly(amidoamine) dendrimers. The formed RGD-modified dendrimer-stabilized Au NSs (RGD-Au DSNSs) are used as a gene delivery vector to complex small interfering RNA (siRNA) for computed tomography (CT) imaging, thermal imaging, photothermal therapy (PTT), and gene therapy of tumors. The results show that the RGD-Au DSNSs are able to compact vascular endothelial growth factor siRNA and specifically deliver siRNA to cancer cells overexpressing α v β 3 integrin. Under near-infrared laser irradiation, the viability of cancer cells is only 20.2% after incubation with the RGD-Au DSNS/siRNA polyplexes, which is much lower than that of cells after single PTT or gene therapy treatment. Furthermore, in vivo results show that the RGD-Au DSNS/siRNA polyplexes enable tumor CT imaging, thermal imaging, PTT, and gene therapy after intratumoral injection. These results indicate that the developed multifunctional nanoconstruct is a promising platform for tumor imaging and combinational PTT and gene therapy. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Science.gov (United States)

Heijs, Dirk-Jan; Malyshev, Victor A.; Knoester, Jasper

2004-09-01

We theoretically study the trapping time distribution and the efficiency of the excitation energy transport in dendritic systems. Trapping of excitations, created at the periphery of the dendrimer, on a trap located at its core, is used as a probe of the efficiency of the energy transport across the dendrimer. The transport process is treated as incoherent hopping of excitations between nearest-neighbor dendrimer units and is described using a rate equation. We account for radiative and nonradiative decay of the excitations while diffusing across the dendrimer. We derive exact expressions for the Laplace transform of the trapping time distribution and the efficiency of trapping, and analyze those for various realizations of the energy bias, number of dendrimer generations, and relative rates for decay and hopping. We show that the essential parameter that governs the trapping efficiency is the product of the on-site excitation decay rate and the trapping time (mean first passage time) in the absence of decay.

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...

Synthesis and evaluation of a glutamic acid-modified hPAMAM complex as a promising versatile gene carrier.

Science.gov (United States)

Hemmati, Mohammad; Kazemi, Bahram; Najafi, Farhood; Zarebkohan, Amir; Shirkoohi, Reza

2016-01-01

Hyperbranched poly(amidoamine) (HPAMAM), structurally analogous to polyamidoamine dendrimer (PAMAM) dendrimers, has been suggested to be an effective carrier for gene delivery. In the present study, glutamic acid-modified hPAMAM was developed as a novel non-viral gene carrier for the first time. The hPAMAM was synthesized by using a modified one-pot method. DNA was found to be bound to hPAMAM at different weight ratios (WhPAMAM/WDNA). The resulting HPAMAM-Glu20 was able to efficiently protect the encapsulated-DNA against degradation for over 2 h. In addition to low cytotoxicity, the transfection efficiency of hPAMAM-Glu20 represented much higher (p glutamic amino acid (Glu)-based gene delivery is an economical, effective and biocompatible method.

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

New Dendrimer-Based Nanoparticles Enhance Curcumin Solubility.

Science.gov (United States)

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

2017-03-01

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

Development of TREN dendrimers over mesoporous SBA-15 for CO2 adsorption

International Nuclear Information System (INIS)

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

2010-01-01

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

Star-shaped Poly(2-oxazoline)s by Dendrimer Endcapping

NARCIS (Netherlands)

Lambermont-Thijs, H.M.L.; Fijten, M.W.M.; Schubert, U.S.; Hoogenboom, R.

2011-01-01

The synthesis of star-shaped poly(2-ethyl-2-oxazoline) is reported by direct end-capping of the living polymer chains with dendritic multiamines. The end-capping kinetics after addition of a first generation polypropylenimine dendrimer are discussed based on monitoring by size exclusion

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

International Nuclear Information System (INIS)

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

2005-01-01

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

Tailoring silver nanoparticle construction using dendrimer templated silica networks

International Nuclear Information System (INIS)

Liu Xiaojun; Kakkar, Ashok

2008-01-01

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

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

Science.gov (United States)

Wang, Bo

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

Folate coupled poly(ethyleneglycol) conjugates of anionic poly(amidoamine) dendrimer for inflammatory tissue specific drug delivery.

Science.gov (United States)

Chandrasekar, Durairaj; Sistla, Ramakrishna; Ahmad, Farhan J; Khar, Roop K; Diwan, Prakash V

2007-07-01

Folate receptor is overexpressed on the activated (but not quiescent) macrophages in both animal models and human patients with naturally occurring rheumatoid arthritis. The aim of this study was to prepare folate targeted poly(ethylene glycol) (PEG) conjugates of anionic dendrimer (G3.5 PAMAM) as targeted drug delivery systems to inflammation and to investigate its biodistribution pattern in arthritic rats. Folate-PEG-PAMAM conjugates, with different degrees of substitution were synthesized by a two-step reaction through a carbodiimide-mediated coupling reaction and loaded with indomethacin. Folate-PEG conjugation increased the drug loading efficiency by 10- to 20-fold and the in vitro release profile indicated controlled release of drug. The plasma pharmacokinetic parameters indicated an increased AUC, circulatory half-life and mean residence time for the folate-PEG conjugates. The tissue distribution studies revealed significantly lesser uptake by stomach for the folate-PEG conjugates, thereby limiting gastric-related side effect. The time-averaged relative drug exposure (r(e)) of the drug in paw for the folate-PEG conjugates ranged from 1.81 to 2.37. The overall drug targeting efficiency (T(e)) was highest for folate-PEG conjugate (3.44) when compared to native dendrimer (1.72). The folate-PEG-PAMAM conjugates are the ideal choice for targeted delivery of antiarthritic drugs to inflammation with reduced side-effects and higher targeting efficiency. Copyright 2007 Wiley Periodicals, Inc.

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.

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 ...

Transepithelial and endothelial transport of poly (amidoamine) dendrimers.

Science.gov (United States)

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

2005-12-14

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

Study of Dendrimers by Topological Indices

Directory of Open Access Journals (Sweden)

Soleimani Najmeh

2017-12-01

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

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

International Nuclear Information System (INIS)

Chen, Wei-Ren

2008-01-01

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

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

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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.

Synthesis of PEGylated polyglutamic acid peptide dendrimer and its application in dissolving thrombus.

Science.gov (United States)

Zhang, Shao-Fei; Gao, Chunmei; Lü, Shaoyu; He, Jiujun; Liu, Mingzhu; Wu, Can; Liu, Yijing; Zhang, Xinyu; Liu, Zhen

2017-11-01

Nattokinase (NK) has been used as a new generation thrombolytic drug, due to its high safety, low cost and low side effects. However, it is sensitive to external environment and may lose the enzyme activity easily. Peptide dendrimer possesses functional groups on its surface, adjustable sizes, biodegradability, biocompatibility, and low toxicity, which could be used as ideal carrier for drug protection and delivery. Demonstrated for the first time in this paper, a PEGylated dendrimer (G n -PEG-G n ) composed of polyglutamic acid is designed and synthesized as delivery platform of NK for thrombus treatment. A panel of PEGylated dendrimers with three different generations of 2, 3, 4 was prepared to investigate the effect of dendrimer architecture on the properties and therapeutic efficacy of the resultant NK-loaded delivery systems in terms of the morphology, dimension and enzyme activity. The results demonstrated that the NK-loaded G 3 -PEG-G 3 (G 3 -PEG-G 3 /NK ratio of 6/1), of all the formulations, displayed the optimal enzyme activity for dissolving thrombus in vitro, thus offering great potential for the treatment of thrombus. Copyright © 2017 Elsevier B.V. All rights reserved.

Aggregation is a critical cause of poor transfer into the brain tissue of intravenously administered cationic PAMAM dendrimer nanoparticles

Science.gov (United States)

Kurokawa, Yoshika; Sone, Hideko; Win-Shwe, Tin-Tin; Zeng, Yang; Kimura, Hiroyuki; Koyama, Yosuke; Yagi, Yusuke; Matsui, Yasuto; Yamazaki, Masashi; Hirano, Seishiro

2017-01-01

Dendrimers have been expected as excellent nanodevices for brain medication. An amine-terminated polyamidoamine dendrimer (PD), an unmodified plain type of PD, has the obvious disadvantage of cytotoxicity, but still serves as an attractive molecule because it easily adheres to the cell surface, facilitating easy cellular uptake. Single-photon emission computed tomographic imaging of a mouse following intravenous injection of a radiolabeled PD failed to reveal any signal in the intracranial region. Furthermore, examination of the permeability of PD particles across the blood–brain barrier (BBB) in vitro using a commercially available kit revealed poor permeability of the nanoparticles, which was suppressed by an inhibitor of caveolae-mediated endocytosis, but not by an inhibitor of macropinocytosis. Physicochemical analysis of the PD revealed that cationic PDs are likely to aggregate promptly upon mixing with body fluids and that this prompt aggregation is probably driven by non-Derjaguin–Landau– Verwey–Overbeek attractive forces originating from the surrounding divalent ions. Atomic force microscopy observation of a freshly cleaved mica plate soaked in dendrimer suspension (culture media) confirmed prompt aggregation. Our study revealed poor transfer of intravenously administered cationic PDs into the intracranial nervous tissue, and the results of our analysis suggested that this was largely attributable to the reduced BBB permeability arising from the propensity of the particles to promptly aggregate upon mixing with body fluids. PMID:28579780

PREPARATION OF CHEMICALLY WELL-DEFINED CARBOHYDRATE DENDRIMER CONJUGATES

DEFF Research Database (Denmark)

2004-01-01

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

Tautomeric forms of PPI dendrimers functionalized with 4-(4′-ethoxybenzoyloxy)salicylaldehyde chromophores

International Nuclear Information System (INIS)

Franckevičius, M.; Vaišnoras, R.; Marcos, M.; Serrano, J.L.; Gruodis, A.; Galikova, N.; Gulbinas, V.

2012-01-01

Highlights: ► SA chromophore groups are formed by bonding terminal groups to PPI dendrimers. ► SA chromophore groups reveal four most stable tautomeric forms. ► Tautomeric properties of SA groups depend on the dendrimer generation and solvent. ► Aggregation of SA chromophores facilitates formation of the trans-keto tautomers. ► Fluorescence of PPI SA dendrimers is attributed to nπ ∗ states of keto tautomers. -- Abstract: Bonding of the promesogenic unit derived from 4-(4′-ethoxybenzoyloxy)salicylaldehyde to the amino terminated PPI dendrimer chains results in formation of the salicylidenimine chromophore groups. Absorption and fluorescence investigations of the dendrimer solutions supported by the quantum chemistry calculations revealed that the chromophore groups may exist in enol and keto tautomeric forms with relative concentrations depending on the dendrimer generation and solvent. The dendrimer fluorescence is attributed to nπ ∗ states of keto tautomers which may also be formed from excited enol tautomers.

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.

Supramolecular assembly of a series of chiral dendrimers in interfacial films

International Nuclear Information System (INIS)

Yuan Jing; Deng Guojun; Fan Qinghua; Liu Minghua

2004-01-01

Supramolecular assembly and interfacial properties of a series of novel binaphthyl containing dendrimers from generation 1 through generation 4 have been investigated at the air/water interface and in solid substrates. Due to the lack of either long alkyl chains or strong hydrophilic groups, the dendrimer molecules tend to aggregate together to form stable two-dimensional ultrathin films, as verified by π-A and A-t measurements. Atomic force microscope (AFM) measurements of the transferred one-layer ultrathin films indicate that all the dendrimers show disk-like morphologies, which could be varied in particle size upon changing the surface pressure. The height profiles reveal that the height of the disks is between that of a monolayer and a bilayer, indicating that they are formed due to the aggregation of dendrimers with a distortion and/or partial overlapping. Circular dichroism (CD) spectra of the transferred multilayer films show Cotton effects due to the exciton couplet of the aromatic moieties adjacent to the bis(diphenylphosphino)-binaphthyl moiety, which is an active catalytic site for the dendrimer. With the increment of the generation, the intensity of the Cotton effects increased, suggesting that the optical active site of the dendrimer can be controlled by the outside wedge

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

OpenAIRE

Gneid, Hassan

2014-01-01

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

Short- and long-term cytotoxic effects of doxorubicin conjugates with dendrimers and vector protein on MCF-7/MDR1 chemoresistant breast cancer cells

Science.gov (United States)

Zamulaeva, I. A.; Matchuk, O. N.; Churyukina, K. A.; Kudryavtzev, V. A.; Yabbarov, N. G.; Nikolskaya, E. D.; Zhunina, O. A.; Kondrasheva, I. G.; Severin, E. S.

2017-09-01

The dendritic polymers (dendrimers) are perspective nanocontainers for targeted transport of anticancer drugs to tumor cells. We used polyamidoamine dendrimers of the second generation (G2) covalently conjugated with doxorubicin (Dox) and vector protein - recombinant third domain (3D) of alpha-fetoprotein. The objects of the study were MCF-7/MDR1 breast cancer cells, which demonstrated resistance to traditional anticancer agents due to high expression of P-glycoprotein. Effects of free Dox, G2 dendrimers loaded with Dox (G2-Dox), or conjugates of dendrimers with the vector protein and Dox (3D-G2-Dox) were assessed by the criteria of surviving cell number and clonogenic activity 24 hours and 11 days after treatment with the agents at Dox concentration of 2.5 μM, correspondingly. Flow cytometry was used to evaluate accumulation of Dox immediately after the treatment with the agents and removal of Dox during 24 hours of incubation in agent-free medium following by the treatment. Intracellular localization of Dox was studied using laser scanning microscopy. 3D-G2-Dox demonstrated the highest accumulation and the weakest removal from the cells in comparison with all other agents. The use of free Dox, G2-Dox, or 3D-G2-Dox resulted in a significant decrease in number of surviving cells by approximately 25-30% compared to the control (p ≤ 0.01). However, the most pronounced decrease in the clonogenic ability of cells was observed in the 3D-G2-Dox group (to 19% compared to the control, p < 0.01). Taking into account the previously obtained data on the extremely low 3D-G2-Dox accumulation in normal cells, it can be concluded that further development of 3D-G2-Dox as a possible anticancer drug is a promising way to overcome multiple drug resistance with minimal impact on normal cells.

Biphasic interactions between a cationic dendrimer and actin.

Science.gov (United States)

Ruenraroengsak, Pakatip; Florence, Alexander T

2010-12-01

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

Alcohol biosensing by polyamidoamine (PAMAM)/cysteamine/alcohol oxidase-modified gold electrode.

Science.gov (United States)

Akin, Mehriban; Yuksel, Merve; Geyik, Caner; Odaci, Dilek; Bluma, Arne; Höpfner, Tim; Beutel, Sascha; Scheper, Thomas; Timur, Suna

2010-01-01

A highly stable and sensitive amperometric alcohol biosensor was developed by immobilizing alcohol oxidase (AOX) through Polyamidoamine (PAMAM) dendrimers on a cysteamine-modified gold electrode surface. Ethanol determination is based on the consumption of dissolved oxygen content due to the enzymatic reaction. The decrease in oxygen level was monitored at -0.7 V vs. Ag/AgCl and correlated with ethanol concentration. Optimization of variables affecting the system was performed. The optimized ethanol biosensor showed a wide linearity from 0.025 to 1.0 mM with 100 s response time and detection limit of (LOD) 0.016 mM. In the characterization studies, besides linearity some parameters such as operational and storage stability, reproducibility, repeatability, and substrate specificity were studied in detail. Stability studies showed a good preservation of the bioanalytical properties of the sensor, 67% of its initial sensitivity was kept after 1 month storage at 4 degrees C. The analytical characteristics of the system were also evaluated for alcohol determination in flow injection analysis (FIA) mode. Finally, proposed biosensor was applied for ethanol analysis in various alcoholic beverage as well as offline monitoring of alcohol production through the yeast cultivation. Copyright 2010 American Institute of Chemical Engineers

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....

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

Science.gov (United States)

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

2014-10-06

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

TPP-dendrimer nanocarriers for siRNA delivery to the pulmonary epithelium and their dry powder and metered-dose inhaler formulations.

Science.gov (United States)

Bielski, Elizabeth; Zhong, Qian; Mirza, Hamad; Brown, Matthew; Molla, Ashura; Carvajal, Teresa; da Rocha, Sandro R P

2017-07-15

The regulation of genes utilizing the RNA interference (RNAi) mechanism via the delivery of synthetic siRNA has great potential in the treatment of a variety of lung diseases. However, the delivery of siRNA to the lungs is challenging due to the poor bioavailability of siRNA when delivered intraveneously, and difficulty in formulating and maintaining the activity of free siRNA when delivered directly to the lungs using inhalation devices. The use of non-viral vectors such as cationic dendrimers can help enhance the stability of siRNA and its delivery to the cell cytosol. Therefore, in this work, we investigate the ability of a triphenylphosphonium (TPP) modified generation 4 poly(amidoamine) (PAMAM) dendrimer (G4NH 2 -TPP) to enhance the in vitro transfection efficiency of siRNA in a model of the pulmonary epithelium and their aerosol formulations in pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs). Complexes of siRNA and G4NH 2 -TPP were prepared with varying TPP densities and increasing N/P ratios. The complexation efficiency was modulated by the presence of the TPP on the dendrimer surface, allowing for a looser complexation compared to unmodified dendrimer as determined by gel electrophoresis and polyanion competition assay. An increase in TPP density and N/P ratio led to an increase in the in vitro gene knockdown of stably green fluorescent protein (eGFP) expressing lung alveolar epithelial (A549) cells. G4NH 2 -12TPP dendriplexes (G4NH 2 PAMAM dendrimers containing 12 TPP molecules on the surface complexed with siRNA) at N/P ratio 30 showed the highest in vitro gene knockdown efficiency. To assess the potential of TPP-dendriplexes for pulmonary use, we also developed micron particle technologies for both pMDIs and DPIs and determined their aerosol characteristics utilizing an Andersen Cascade Impactor (ACI). Mannitol microparticles encapsulating 12TPP-dendriplexes were shown to be effective in producing aerosols suitable for deep lung

The use of dendrimers as high-performance shells for round-trip energy transfer: efficient trans-cis photoisomerization from an excited triplet state produced within a dendrimer shell.

Science.gov (United States)

Miura, Yousuke; Momotake, Atsuya; Takeuchi, Keiichirou; Arai, Tatsuo

2011-01-01

A series of stilbene-cored poly(benzyl ether) dendrimers with benzophenone peripheries were synthesized and their photophysical and photochemical properties were studied. Fluorescence studies revealed that singlet-singlet energy transfer (SSET) from the stilbene core to the benzophenone units took place efficiently in dendrimers of all generations. Similarly, phosphorescence and time-resolved spectroscopic measurements indicated efficient triplet-triplet energy transfer (TTET) from the benzophenone periphery to the stilbene core. Upon excitation at 310 nm, the stilbene core isomerizes via an energy round trip within the dendrimer shell. The quantum yields for the energy round trip (Φ(ERT)), defined as the product of the quantum yields of SSET, intersystem crossing, and TTET (Φ(ERT) = Φ(SS)Φ(isc)Φ(TT)), were extremely high for all generations--99%, 95% and 94% for G1, G2, and G3, respectively--which means that the excitation energy of the dendrimer core was transferred to the dendrimer periphery and back to the core almost quantitatively. The quantum yield for photoisomerization of G1-G3 via an energy round trip was higher than for other stilbene-cored dendrimers, which mainly isomerize from the excited singlet state. Photostability in the dendrimers was also demonstrated and discussed.

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

Biodistribution, pharmacokinetics, and toxicity of dendrimer-coated iron oxide nanoparticles in BALB/c mice

Directory of Open Access Journals (Sweden)

Salimi M

2018-03-01

Full Text Available Marzieh Salimi,1,2 Saeed Sarkar,1,2 Samaneh Fathi,3 Ali Mohammad Alizadeh,4 Reza Saber,2,3 Fatemeh Moradi,5 Hamid Delavari6 1Department of Medical Physics and Biomedical Engineering, Tehran University of Medical Sciences, Tehran, Iran; 2Research Center of Science and Technology in Medicine, Tehran University of Medical Sciences, Tehran, Iran; 3Department of Medical Nanotechnology, Tehran University of Medical Sciences, Tehran, Iran; 4Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran; 5Department of Medical Physiology, Tehran University of Medical Sciences, Tehran, Iran; 6Department of Materials Science and Engineering, Tarbiat Modares University, Tehran, Iran Background: The possibility of using a specific nanoparticle in nanomedicine highly depends on its biodistribution profile and biocompatibility. Due to growing demand for iron oxide nanoparticles (IONPs and dendrimers in biomedical applications, this study was performed to assess the biodistribution, pharmacokinetics, and toxicity of dendrimer-coated iron oxide nanoparticles (G4@IONPs. Materials and methods: IONPs were synthesized via co-precipitation and coated with the fourth generation (G4 of polyamidoamine (PAMAM dendrimer. To determine the biodistribution, 5 mg/mL G4@IONPs suspension was intraperitoneally injected into tumor-bearing BALB/c mice, and iron levels in blood and various organs, including the lung, liver, brain, heart, tumor, and kidney, were measured by inductively coupled plasma mass spectrometry (ICP-MS at 4, 8, 12, and 24 h after injection. Also, to investigate the toxicity of G4@IONPs, different concentrations of G4@IONPs were injected into BALB/c mice, and blood, renal, and hepatic factors were measured. Furthermore, histopathological staining was performed to investigate the effect of G4@IONPs on the liver and kidney tissues. Results: The results showed that the iron content was higher in the kidney, liver, and lung tissues 24 h after

Dendrimer sensors probed with neutron reflectometry

International Nuclear Information System (INIS)

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

2009-01-01

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

Structure of DNA-Functionalized Dendrimer Nanoparticles

OpenAIRE

Kumar, Mattaparthi Venkata Satish; Maiti, Prabal K

2012-01-01

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

Optical absorption and energy transfer processes in dendrimers

International Nuclear Information System (INIS)

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

2004-01-01

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

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

International Nuclear Information System (INIS)

Masrour, R.; Jabar, A.

2016-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2016-11-01

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

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

International Nuclear Information System (INIS)

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

2006-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2006-11-14

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

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

Science.gov (United States)

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

2006-11-01

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

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

Science.gov (United States)

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

2003-10-01

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

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

Structural properties of dendrimer-colloid mixtures

International Nuclear Information System (INIS)

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

2012-01-01

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

Structural properties of star-like dendrimers in solution

International Nuclear Information System (INIS)

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

2002-01-01

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

Structure-skin permeability relationship of dendrimers.

Science.gov (United States)

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

2011-09-01

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

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

International Nuclear Information System (INIS)

Fei, Wenjuan; Chen, Feifei; Sun, Li; Li, Qianhua; Wu, Ying; Yang, Jianping

2014-01-01

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

Energy transport in dendrimers

International Nuclear Information System (INIS)

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

2006-01-01

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

Energy transport in dendrimers

Energy Technology Data Exchange (ETDEWEB)

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

2006-07-15

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

Preclinical studies of dendrimer prodrugs.

Science.gov (United States)

Kojima, Chie

2015-01-01

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

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

Science.gov (United States)

Uram, Łukasz; Szuster, Magdalena; Filipowicz, Aleksandra; Gargasz, Krzysztof; Wołowiec, Stanisław; Wałajtys-Rode, Elżbieta

2015-01-01

The intracellular localization and colocalization of a fluorescently labeled G3 amine-terminated cationic polyamidoamine (PAMAM) dendrimer and its biotin–pyridoxal (BC-PAMAM) bioconjugate were investigated in a concentration-dependent manner in normal human fibroblast (BJ) and squamous epithelial carcinoma (SCC-15) cell lines. After 24 hours treatment, both cell lines revealed different patterns of intracellular dendrimer accumulation depending on their cytotoxic effects. Cancer cells exhibited much higher (20-fold) tolerance for native PAMAM treatment than fibroblasts, whereas BC-PAMAM was significantly toxic only for fibroblasts at 50 µM concentration. Fibroblasts accumulated the native and bioconjugated dendrimers in a concentration-dependent manner at nontoxic range of concentration, with significantly lower bioconjugate loading. After reaching the cytotoxicity level, fluorescein isothiocyanate-PAMAM accumulation remains at high, comparable level. In cancer cells, native PAMAM loading at higher, but not cytotoxic concentrations, was kept at constant level with a sharp increase at toxic concentration. Mander’s coefficient calculated for fibroblasts and cancer cells confirmed more efficient native PAMAM penetration as compared to BC-PAMAM. Significant differences in nuclear dendrimer penetration were observed for both cell lines. In cancer cells, PAMAM signals amounted to ~25%–35% of the total nuclei area at all investigated concentrations, with lower level (15%–25%) observed for BC-PAMAM. In fibroblasts, the dendrimer nuclear signal amounted to 15% at nontoxic and up to 70% at toxic concentrations, whereas BC-PAMAM remained at a lower concentration-dependent level (0.3%–20%). Mitochondrial localization of PAMAM and BC-PAMAM revealed similar patterns in both cell lines, depending on the extracellular dendrimer concentration, and presented significantly lower signals from BC-PAMAM, which correlated well with the cytotoxicity. PMID:26379435

Optical absorption in dendrimers

International Nuclear Information System (INIS)

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

2004-01-01

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

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

Directory of Open Access Journals (Sweden)

Marco Marradi

2012-06-01

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

Synthesis and protonation behavior of carboxylate-functionalized poly(propylene imine) dendrimers

NARCIS (Netherlands)

Duijvenbode, van R.C.; Rajanayagam, A.; Koper, G.J.M.; Baars, M.W.P.L.; Waal, de B.F.M.; Meijer, E.W.; Borkovec, M.

2000-01-01

Five generations of carboxylate-functionalized poly(propyleneimine) dendrimers have been synthesized starting from a double Michael addition of amine-functionalized poly(propyleneimine) dendrimers to methyl acrylate followed by basic hydrolysis using LiOH in a water/methanol mixture. The dendritic

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

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

DEFF Research Database (Denmark)

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

2002-01-01

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

Energy transfer to xanthene dyes in dansylated POPAM dendrimers

Science.gov (United States)

Aumanen, Jukka; Korppi-Tommola, Jouko

2011-12-01

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

Exciton localization-delocalization transition in an extended dendrimer

Energy Technology Data Exchange (ETDEWEB)

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

2013-12-21

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

Exciton localization-delocalization transition in an extended dendrimer

International Nuclear Information System (INIS)

Pouthier, Vincent

2013-01-01

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

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.

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

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

2016-11-01

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

Chondroitin sulfate-functionalized polyamidoamine as a tumor-targeted carrier for miR-34a delivery.

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Chen, Wenqi; Liu, Yong; Liang, Xiao; Huang, Yu; Li, Quanshun

2017-07-15

Chondroitin sulfate (CS) was modified on a polyamidoamine dendrimer (PAMAM) through Michael addition to construct a tumor-targeted carrier CS-PAMAM for miR-34a delivery. The derivative CS-PAMAM was demonstrated to achieve an efficient cellular uptake of miR-34a in a CD44-dependent endocytosis way and further facilitate the endosomal escape of miR-34a after 4h. Through the miR-34a delivery, obvious inhibition of cell proliferation could be detected which was attributed to the enhancement of cell apoptosis and cell cycle arrest, and meanwhile the cell migration and invasion has been observed to be inhibited. Finally, the intravenous injection of CS-PAMAM/miR-34a formulation into mice bearing human lung adenocarcinoma cell A549 xenografts could efficiently inhibit the tumor growth and induce the tumor apoptosis owing to the enhanced accumulation of miR-34a in tumor tissue. Overall, CS-PAMAM is potential to be used as a tumor-targeted oligonucleotide carrier for achieving tumor gene therapy. The cationic dendrimer PAMAM was modified by chondroitin sulfate (CS) through Michael addition to construct a tumor-targeted carrier CS-PAMAM for miR-34a delivery. The introduction of CS could achieve an efficient cellular uptake and intracellular transfection of miR-34a in a CD44-dependent endocytosis manner. The miR-34a delivery could execute the anti-proliferation activity by simultaneously inducing cell apoptosis and cell cycle arrest, and also the anti-migration activity. The CS-PAMAM-mediated systemic delivery of miR-34a showed significant inhibition of tumor growth and induction of tumor apoptosis using a mice model of subcutaneously implanted tumors. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Diglycolamide-functionalized dendrimers : Studies on Americium(III) pertraction from radioactive waste

NARCIS (Netherlands)

Ansari, Seraj A.; Mohapatra, Prasanta K.; Leoncini, Andrea; Huskens, Jurriaan; Verboom, Willem

2017-01-01

Diglycolamide (DGA)-functionalized poly(propylene imine) diaminobutane dendrimers were evaluated as the carrier in supported liquid membranes (SLMs) for selective recovery of trivalent actinides over uranium. The 0, 1st, and 2nd generation dendrimers with 2, 4, and 8 DGA moieties, termed as LI, LII,

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

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Kaltenbach, Miriam; Stein, Viktor; Hollfelder, Florian

2011-09-19

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

Dendrimer Prodrugs

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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.

Highly efficient single-layer dendrimer light-emitting diodes with balanced charge transport

Science.gov (United States)

Anthopoulos, Thomas D.; Markham, Jonathan P. J.; Namdas, Ebinazar B.; Samuel, Ifor D. W.; Lo, Shih-Chun; Burn, Paul L.

2003-06-01

High-efficiency single-layer-solution-processed green light-emitting diodes based on a phosphorescent dendrimer are demonstrated. A peak external quantum efficiency of 10.4% (35 cd/A) was measured for a first generation fac-tris(2-phenylpyridine) iridium cored dendrimer when blended with 4,4'-bis(N-carbazolyl)biphenyl and electron transporting 1,3,5-tris(2-N-phenylbenzimidazolyl)benzene at 8.1 V. A maximum power efficiency of 12.8 lm/W was measured also at 8.1 V and 550 cd/m2. These results indicate that, by simple blending of bipolar and electron-transporting molecules, highly efficient light-emitting diodes can be made employing a very simple device structure.

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

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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.

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

Science.gov (United States)

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

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

EXAFS Characterization of Dendrimer-Derived Pt/γ-Al2O3

International Nuclear Information System (INIS)

Siani, A.; Alexeev, O. S.; Williams, C. T.; Ploehn, H. J.; Amiridis, M. D.

2007-01-01

The various steps involved in the preparation of a Pt/γ-Al2O3 material using hydroxyl-terminated generation four (G4OH) PAMAM dendrimers as templates were monitored by EXAFS. The results indicate that Cl ligands in the Pt precursors (H2PtCl6 and K2PtCl4) were partially replaced by aquo ligands upon hydrolysis to form [PtCl3(H2O)3]+ and [PtCl2(H2O)2] species. After interaction of such species with G4OH, Cl ligands from the first coordination shell of Pt were further replaced by nitrogen atoms from the dendrimer interior, indicating the complexation of Pt with the dendrimer. This process was accompanied by a transfer of the electron density from the dendrimer to Pt, indicating that the former plays the role of a ligand. Following treatment of the H2PtCl6/G4OH and K2PtCl4/G4OH composites with NaBH4, no substantial changes were detecteded in the electronic or coordination environment of Pt, and no formation of metal nanoparticles was observed. However, when the reduction treatment was performed with H2, the formation of extremely small Pt clusters incorporating no more than 4 Pt atoms was observed. These Pt species remained strongly bonded to the dendrimer and their nuclearity depends on the length of the H2 treatment. Formation of Pt nanoparticles with an average diameter of approximately 10 A was finally observed after the deposition of H2PtCl6/G4OH on γ-Al2O3 and drying, suggesting that their formation may be related to the collapse of the dendrimer structure. The Pt nanoparticles formed appear to have high mobility, since subsequent thermal treatment in O2/H2 led to further sintering

A transgenic rat hepatocyte - Kupffer cell co-culture model for evaluation of direct and macrophage-related effect of poly(amidoamine) dendrimers.

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Jemnitz, Katalin; Bátai-Konczos, Attila; Szabó, Mónika; Ioja, Enikő; Kolacsek, Orsolya; Orbán, Tamás I; Török, György; Homolya, László; Kovács, Eszter; Jablonkai, István; Veres, Zsuzsa

2017-02-01

Increasing number of papers demonstrate that Kupffer cells (KCs) play a role in the development of drug induced liver injury (DILI). Furthermore, elevated intracellular Ca 2+ level of hepatocytes is considered as a common marker of DILI. Here we applied an in vitro model based on hepatocyte mono- and hepatocyte/KC co-cultures (H/KC) isolated from transgenic rats stably expressing the GCaMP2 fluorescent Ca 2+ sensor protein to investigate the effects of polycationic (G5), polyanionic (G4.5) and polyethylene-glycol coated neutral (G5 Peg) dendrimers known to accumulate in the liver, primarily in KCs. Following dendrimer exposure, hepatocyte homeostasis was measured by MTT cytotoxicity assay and by Ca 2+ imaging, while hepatocyte functions were studied by CYP2B1/2 inducibility, and bilirubin and taurocholate transport. G5 was significantly more cytotoxic than G4.5 for hepatocytes and induced Ca 2+ oscillation and sustained Ca 2+ signals at 1μM and10 μM, respectively both in hepatocytes and KCs. Dendrimer-induced Ca 2+ signals in hepatocytes were attenuated by macrophages. Activation of KCs by lipopolysaccharide and G5 decreased the inducibility of CYP2B1/2, which was restored by depleting the KCs with gadolinium-chloride and pentoxyphylline, suggesting a role of macrophages in the hindrance of CYP2B1/2 induction by G5 and lipopolysaccharide. In the H/KC, but not in the hepatocyte mono-culture, G5 reduced the canalicular efflux of bilirubin and stimulated the uptake and canalicular efflux of taurocholate. In conclusion, H/KC provides a good model for the prediction of hepatotoxic potential of drugs, especially of nanomaterials known to be trapped by macrophages, activation of which presumably contributes to DILI. Copyright © 2016 Elsevier B.V. All rights reserved.

Hydrogel of Ketoconazole and PAMAM Dendrimers: Formulation and Antifungal Activity

Directory of Open Access Journals (Sweden)

Elzbieta Tryniszewska

2012-04-01

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

Synergistic effect of amino acids modified on dendrimer surface in gene delivery.

Science.gov (United States)

Wang, Fei; Wang, Yitong; Wang, Hui; Shao, Naimin; Chen, Yuanyuan; Cheng, Yiyun

2014-11-01

Design of an efficient gene vector based on dendrimer remains a great challenge due to the presence of multiple barriers in gene delivery. Single-functionalization on dendrimer cannot overcome all the barriers. In this study, we synthesized a list of single-, dual- and triple-functionalized dendrimers with arginine, phenylalanine and histidine for gene delivery using a one-pot approach. The three amino acids play different roles in gene delivery: arginine is essential in formation of stable complexes, phenylalanine improves cellular uptake efficacy, and histidine increases pH-buffering capacity and minimizes cytotoxicity of the cationic dendrimer. A combination of these amino acids on dendrimer generates a synergistic effect in gene delivery. The dual- and triple-functionalized dendrimers show minimal cytotoxicity on the transfected NIH 3T3 cells. Using this combination strategy, we can obtain triple-functionalized dendrimers with comparable transfection efficacy to several commercial transfection reagents. Such a combination strategy should be applicable to the design of efficient and biocompatible gene vectors for gene delivery. Copyright © 2014 Elsevier Ltd. All rights reserved.

One-, two- and three-photon spectroscopy of π-conjugated dendrimers: cooperative enhancement and coherent domains

International Nuclear Information System (INIS)

Drobizhev, M.; Rebane, A.; Suo, Z.; Spangler, C.W.

2005-01-01

We use wavelength tunable femtosecond pulses to measure intrinsic (simultaneous) two-photon absorption (2PA) and three-photon absorption (3PA) molecular cross section in two series of π-conjugated dendrimers built of identical 4,4'-bis(diphenylamino) stilbene (BDPAS) and 4,4'-bis(diphenylamino) distyrylbenzene (BDPADSB) repeat units. Record large 2PA cross sections, σ 2 =10 -46 cm 4 s are obtained for the largest second-generation BDPAS-based dendrimer, as well as zeroth-generation 4-arm BDPADSB-based dendrimer. In both series, maximum 2PA cross section increases nonlinearly with the number of π-electrons, whereas for higher generations this dependence turns to linear one. 3PA cross section also increases nonlinearly with the size of the system in the series of BDPAS-based molecules, amounting a record large value, σ 3 =10 -79 cm 6 s 2 , for the largest, second-generation dendrimer. We interpret these results in terms of direct inter-branch conjugation, which facilitates cooperative enhancement of the nonlinear-optical response. We propose a simple model which allows us to determine the effective size of coherent domains (extent of conjugation), which, in turn, determines the optimum dendrimer size for most efficient nonlinear response

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

NARCIS (Netherlands)

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

2005-01-01

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

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

Science.gov (United States)

Sadekar, S; Ghandehari, H

2012-05-01

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

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.

Synthesis of Dendrimer Containing Carbazole Unit as a Core Chromophore

International Nuclear Information System (INIS)

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

2012-01-01

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

I. Hole-transporting dendrimers and their use in organic light-emitting devices (OLEDs) and II. Novel layered catalysts containing bipyridinium and zero-valent metal species

Science.gov (United States)

Koene, Shannon Carol

A series of polyaromatic ether/ester dendrimers containing a hole transporting naphthylphenylbenzyl amine at the periphery and a variety of fluorescent dyes at the core has been studied in an effort to observe energy transfer in these species. The dyes incorporated in these dendrimers include 1,4-dihydroxyanthraquinone (quinizarin), Coumarin 343, and a benzopentathiophene. These dendrimers have been incorporated into both single layer and heterostructure organic light emitting devices (OLEDs). In the case of first generation dendrimer OLEDs, excimer/exciplex formation was predominant. In third generation dendrimers, complete energy transfer from the periphery to the dye at the core was observed both in photoluminescence spectra and electroluminescence in OLEDs. Dendrimers containing different dye cores can be combined to achieve color mixing/tuning. In addition, layered catalysts were prepared via both covalent and electrostatic means to achieve the catalytic production of hydrogen peroxide from hydrogen and oxygen. Covalent catalysts were prepared by first growing layers of zirconium and a bipyridinium containing bisphosphonate onto silica particles. Palladium and/or platinum was ion-exchanged into the structure and reduced to the zero valent metal by hydrogen gas. A second set of catalysts was prepared by electrostatically depositing polycations/polyanions onto carboxylate or amine functionalized polystyrene microspheres. Anionic colloidal particles were adsorbed to the polycationic surface. An octacationic viologen oligomer was used in an attempt to increase the affinity of adsorption of the Pd particles to the surface of the microspheres. Catalytic studies of both types of catalysts are herein reported.

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

International Nuclear Information System (INIS)

Ainalem, M.L.; Rennie, A.R.; Campbell, Richard; Edler, Karen; Nylander, Tommy

2009-01-01

The systemic delivery of DNA for gene therapy requires control of DNA compaction by an agent, such a lipid, surfactant or a polymer (e.g. cationic dendrimers) as well as understanding of how this complex interacts with a biological membrane. Poly (amido amine) (PAMAM) dendrimers have been reported to be a promising synthetic gene-transfection agent. We have studied the structure of the complexes formed between DNA and PAMAM dendrimers with SANS, dynamic light scattering and cryo-TEM. Here we noted that the structure of the complex formed strongly depends on the generation of the dendrimer. The results of the adsorption of generation 2 (G2) and 4 (G4) PAMAM dendrimers to surface deposited bilayers, consisting of palmitoyl oleoyl phosphatidyl choline on silicon surface, have been studied using neutron reflectometry (NR). The NR data shows that the dendrimers are able to penetrate the bilayer. However, the complex is less able to penetrate the bilayer, but rather stays on the top of the bilayer. The dendrimers appear slightly flattened on the surface in comparison with their size in bulk as determined by light scattering. We will also report on the interfacial behavior of the DNA-PAMAM complexes at other types of studies of interfaces, important for biomedical applications, where NR has allowed us to determine the layer structure and composition. (author)

Conformational and Structural Properties of High Functionality Dendrimer-like Star Polymers Synthesized from Living Polymerization Techniques; TOPICAL

International Nuclear Information System (INIS)

Pople, John A.

2001-01-01

The design, synthesis and solution properties of dendritic-linear hybrid macromolecules is described. The synthetic strategy employs living ring-opening polymerization in combination with selective and quantitative organic transformations for the preparation of new molecular architectures similar to classical star polymers and dendrimers. The polymers were constructed from high molecular weight poly(e-caprolactone) initiated from the surface hydroxyl groups of dendrimers derived from bis(hydroxymethyl) propionic acid (bis-MPA) in the presence of stannous 2-ethyl hexanoate (Sn(Oct)2). In this way, star and hyperstar poly(e-caprolactones) were elaborated depending on the generation of dendrimer employed. The ROP from these hydroxy groups was found to be a facile process leading to controlled molecular weight, low dispersity products (Mw/Mn) and lt; 1.15. In addition to the use of dendrimers as building blocks to star polymers, functional dendrons derived from bis-MPA were attached to chain ends of the star polymers, yielding structures that closely resemble that of the most advanced dendrimers. Measurements of the solution properties (hydrodynamic volume vs. molecular weight) on the dendritic-linear hybrids show a deviation from linearity, with a lower than expected hydrodynamic volume, analogous to the solution properties of dendrimers of high generation number. The onset of the deviation begins with the polymers initiated from the second generation dendrimer of bis-MPA and becomes more exaggerated with the higher generations. It was found that polymerization amplifies the nonlinear solution behavior of dendrimers. Small angle neutron scattering (SANS) measurements revealed that the radius of gyration scaled with arm functionality (f) as f 2/3, in accordance with the Daoud-Cotton model for many arm star polymer

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.

Preparation of gold nanoparticles in the presence of citric acid-based dendrimers containing periphery hydroxyl groups

International Nuclear Information System (INIS)

Namazi, Hassan; Fard, Ahmad Mohammad Pour

2011-01-01

Highlights: → The most advantage of citric acid-based dendrimers is their novelty from monomeric point of view and their simple preparation method. → The size and also size distribution of Au nanoparticles can be controlled through the choice of the dendrimer generation. → Here, we report the preparation of the stable, isolated and uniform Au nanoparticles with using a simple method in water media.→ It was observed that the size of Au nanoparticles is increased with increasing the generation of dendrimer. - Abstract: In this work, Au nanoparticles were produced with reduction of HAuCl 4 using NaBH 4 in the presence of different generations of citric acid-based dendrimers. The greater water solubility of the newly prepared dendrimers motivated us for the preparation of Au nanoparticles in water media. Therefore, the stable, isolated and uniform type Au nanoparticles were prepared through simple process in water. UV-Vis absorption, high-resolution transmission electronic microscopy (HRTEM), electron diffraction (ED) and energy dispersive X-ray (EDX) methods were used to investigate the morphology and structure determination of the obtained gold nanoparticles.

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

Glycopeptide dendrimers. Part I

Czech Academy of Sciences Publication Activity Database

Niederhafner, Petr; Šebestík, Jaroslav; Ježek, Jan

2008-01-01

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

Synthesis of New Functionalized Citric Acid-based Dendrimers as Nanocarrier Agents for Drug Delivery

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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.

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

OpenAIRE

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

2003-01-01

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

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. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of viologen-phosphorus dendrimers on acetylcholinesterase and butyrylcholinesterase activities.

Science.gov (United States)

Ciepluch, Karol; Weber, Monika; Katir, Nadia; Caminade, Anne-Marie; El Kadib, Abdelkrim; Klajnert, Barbara; Majoral, Jean Pierre; Bryszewska, Maria

2013-03-01

The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is the first step in checking whether new compounds can be considered as drugs for treating neurodegenerative diseases. The effect of viologen-phosphorus dendrimers on AChE and BChE activities was studied. The results show that the effects on the cholinesterase activities depend on dendrimer type and size. Viologen dendrimers can interact with the enzymes in two ways: they can bind either to a peripheral site of the enzyme or to amino acids located near the active site, inhibiting catalysis by both cholinesterases. All tested non-toxic viologen-phosphorus dendrimers inhibited the activities of both cholinesterases, showing their potential as new drugs for treating neurodegenerative diseases. Copyright © 2012 Elsevier B.V. All rights reserved.

Aggregation is a critical cause of poor transfer into the brain tissue of intravenously administered cationic PAMAM dendrimer nanoparticles

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Kurokawa Y

2017-05-01

Full Text Available Yoshika Kurokawa,1 Hideko Sone,1 Tin-Tin Win-Shwe,1 Yang Zeng,1 Hiroyuki Kimura,2 Yosuke Koyama,1 Yusuke Yagi,2 Yasuto Matsui,3 Masashi Yamazaki,4 Seishiro Hirano1 1Center for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba, Ibaraki, 2Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, 3Department of Environmental Engineering, Kyoto University Graduate School of Engineering, Kyoto, 4TIA Center Office, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan Abstract: Dendrimers have been expected as excellent nanodevices for brain medication. An amine-terminated polyamidoamine dendrimer (PD, an unmodified plain type of PD, has the obvious disadvantage of cytotoxicity, but still serves as an attractive molecule because it easily adheres to the cell surface, facilitating easy cellular uptake. Single-photon emission computed tomographic imaging of a mouse following intravenous injection of a radiolabeled PD failed to reveal any signal in the intracranial region. Furthermore, examination of the permeability of PD particles across the blood–brain barrier (BBB in vitro using a commercially available kit revealed poor permeability of the nanoparticles, which was suppressed by an inhibitor of caveolae-mediated endocytosis, but not by an inhibitor of macropinocytosis. Physicochemical analysis of the PD revealed that cationic PDs are likely to aggregate promptly upon mixing with body fluids and that this prompt aggregation is probably driven by non-Derjaguin–Landau–Verwey–Overbeek attractive forces originating from the surrounding divalent ions. Atomic force microscopy observation of a freshly cleaved mica plate soaked in dendrimer suspension (culture media confirmed prompt aggregation. Our study revealed poor transfer of intravenously administered cationic PDs into the intracranial nervous tissue, and the results of our analysis

The neighbourhood polynomial of some families of dendrimers

Science.gov (United States)

Nazri Husin, Mohamad; Hasni, Roslan

2018-04-01

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

Positron annihilation study of polyphenylene dendrimers

International Nuclear Information System (INIS)

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

2003-01-01

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

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

NARCIS (Netherlands)

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

2002-01-01

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

Optical absorption in compact and extended dendrimers

International Nuclear Information System (INIS)

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

2005-01-01

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

Dendrimers for siRNA Delivery

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Swati Biswas

2013-02-01

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

Cylindrical micelles of a POSS amphiphilic dendrimer as nano-reactors for polymerization.

Science.gov (United States)

Weng, Jing-Ting; Yeh, Tso-Fan; Samuel, Ashok Zachariah; Huang, Yi-Fan; Sie, Jyun-Hao; Wu, Kuan-Yi; Peng, Chi-How; Hamaguchi, Hiro-O; Wang, Chien-Lung

2018-02-15

A low generation amphiphilic dendrimer, POSS-AD, which has a POSS core and eight amphiphilic arms, was synthesized and used as a nano-reactor to produce well-defined polymer nano-cylinders. Confirmed by small-angle X-ray scattering (SAXS), Raman and NMR spectrometry, monodispersed cylindrical micelles that contain a hydrophilic cavity with a diameter of 2.09 nm and a length of 4.26 nm were produced via co-assembling POSS-AD with hydrophilic liquids, such as H 2 O and HEMA in hydrophobic solvents. Taking the HEMA/POSS-AD cylindrical micelles as nano-reactors, polymerization of HEMA within the micelles results in polymer nano-cylinders (POSS-ADNPs) with a diameter of 2.24 nm and a length of 5.02 nm. The study confirmed that despite the inability to maintain specific shape in solution, low generation dendrimers form well-defined nano-containers or nano-reactors, which relies on co-assembling with hydrophilic guest molecules. These nano-reactors are robust enough to maintain their shape during the polymerization of the guest molecules. Polymer nano-cylinders with dimensions less than 10 nm can thus be produced from the HEMA/POSS-AD micelles. Since the chemical structure of low-generation dendrimers and the contents of the co-assembled nano-reactors can be easily adjusted, the concept holds the potential for the further developments of low-generation amphiphilic dendrimers.

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

Science.gov (United States)

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

2009-01-01

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

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...

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

[Dendrimers in biomedical sciences and nanotechnology].

Science.gov (United States)

Sekowski, Szymon; Miłowska, Katarzyna; Gabryelak, Teresa

2008-12-30

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

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

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Natalia Wrońska

2015-10-01

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

Engineering CNDP's of dendrimers containing phosphorous interior compositions to produce new emerging properties

Science.gov (United States)

Caminade, Anne-Marie; Majoral, Jean-Pierre

2018-03-01

Phosphorus-containing dendrimers are defined as dendrimers having at least one phosphorus atom at each branching point. In this review, we will show how phosphorhydrazone dendrimers can be modified at will at the level of the core and of the branches, to afford specific properties, such as fluorescence to image biological events. Accelerated methods of synthesis of phosphorus (one step for one generation) will be also displayed, as well as the specific reactivity of P=N-P=S linkages obtained in most of these accelerated method of synthesis, which has led to particularly original dendritic architectures, such as dendrons included in dendrimers. Finally, we will display how modifications of the internal structure of a series of dendrimers having the same type and number of terminal functions can deeply modify their biological anti-inflammatory properties. Among the six critical nanoscale design parameters (CNDP), we will show how two of them, i.e., architecture and elemental composition, have been particularly engineered to modify phosphorus-containing dendrimers, in order to fulfill the desired properties.

Interaction between viologen-phosphorus dendrimers and α-synuclein

International Nuclear Information System (INIS)

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

2013-01-01

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

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

Science.gov (United States)

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

2008-04-01

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

Design and synthesis of pH-sensitive polyamino-ester magneto-dendrimers: Surface functional groups effect on viability of human prostate carcinoma cell lines DU145.

Science.gov (United States)

Dayyani, Nahid; Khoee, Sepideh; Ramazani, Ali

2015-06-15

Novel pH-sensitive, biocompatible and biodegradable magneto-dendrimers with OH and/or NH2 functional groups based on poly amino-ester were synthesized for delivery of anti-cancer drugs. Magnetite nanoparticles (MNPs) were synthesized by the co-precipitation method and their surfaces were modified by 3-aminopropyl triethoxysilane. The first and second generations of the magneto-dendrimer with hydroxyl end groups were produced by sequential acrylation and Michael addition reactions using the required amounts of acryloyl chloride and diethanolamine, respectively. The dendrimer containing amino functional surface groups up to second generation was synthesized by the same method using the necessary amounts of acryloyl chloride and ethylenediamine. These dendrimers were fully characterized by the Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), dynamic light scattering (DLS) and zeta potential analysis, vibrating-sample magnetometer (VSM), scanning electron microscope (SEM), transmission electron microscopy (TEM) and selected area electron diffraction (SAED). In-vitro release profiles of the drug-loaded magnetic nanoparticles and their cytotoxicity assay were investigated at two pHs (7.4 and 5.8). The hydrolytic degradation behavior of magneto-dendrimers was evaluated in PBS buffer. Our research suggests that magneto-dendrimers having amine or hydroxyl functional groups could be considered as the suitable nanocarriers for therapy applications. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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

International Nuclear Information System (INIS)

Ciepluch, Karol; Katir, Nadia; El Kadib, Abdelkrim; Weber, Monika; Caminade, Anne-Marie; Bousmina, Mostapha; Pierre Majoral, Jean; Bryszewska, Maria

2012-01-01

This work deals with photo-physical and structural interactions between viologen phosphorus dendrimers and human serum albumin (HSA). Viologens are derivatives of 4,4′-bipyridinium salts. Aiming to rationalize the parameters governing such interactions eight types of these polycationic dendrimers in which the generation, the number of charges, the nature of the core and of the terminal groups vary from one to another, were designed and used. The influence of viologen-based dendrimers' on human serum albumin has been investigated. The photo-physical interactions of the two systems have been monitored by fluorescence quenching of free L-tryptophan and of HSA tryptophan residue. Additionally, using circular dichroism (CD) the effect of dendrimers on the secondary structure of albumin was measured. The obtained results show that viologen dendrimers interact with human serum albumin quenching its fluorescence either by collisional (dynamic) way or by forming complexes in a ground state (static quenching). In some cases the quenching is accompanied by changes of the secondary structure of HSA. - Highlights: ► Photo-physical interactions between viologen phosphorus dendrimers and human serum albumin (HSA) were investigated. ► The viologen dendrimers can quench the fluorescence of tryptophan in HSA. ► CD spectra to explain the changes in secondary structure of albumin after exposition of dendrimers.

High-efficiency synthesis of dendrimer-like poly(ethylene oxide) via “arm-first” approach

KAUST Repository

Zhu, Saisai

2017-04-14

In this study, a dendrimer-like polymer based on poly(ethylene oxide) (PEO) was synthesized through a combination of anionic ring-opening polymerization (AROP) and click reaction via arm-first method. Firstly, the polymeric arm, a linear PEO with one alkynyl group and two bromo groups, was synthesized by AROP of ethylene oxide followed by functionalization with propargyl bromide and esterified with 2-bromopropionic bromide. Second, a star PEO carrying three azide groups was synthesized though AROP of ethylene oxide used 1,1,1-tris(hydrosymethyl) ethane as initiator followed esterificated with 2-bromopropionic acid and azidation. By azide–alkyne click reactions between the azide-terminated PEO star polymer and linear PEO with functionalization alkynyl group, a three generation dendrimer-like PEO, G3-PEO-24Br, was successfully synthesized. The resulting polymers were observed to have precisely controlled molecular weights and compositions with narrow molecular weight distributions.

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-02-15

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

On the blue emission of a novel solution-processed stilbenoid dendrimer thin film for OLED displays

Energy Technology Data Exchange (ETDEWEB)

Coya, C. [Escuela Superior de Ciencias Experimentales y Tecnologia, Universidad Rey Juan Carlos, 28933 Madrid (Spain)], E-mail: carmen.coya@urjc.es; Andres, A. de [Instituto de Ciencia de Materiales de Madrid, CSIC, Cantoblanco, 28049 Madrid (Spain); Gomez, R.; Seoane, C.; Segura, J.L. [Departamento de Quimica Organica, Facultad de Ciencias Quimicas, Universidad Complutense, 28040 Madrid (Spain)

2008-05-15

A novel blue fluorescent first generation stilbenoid dendrimer built on the 1,3,5-benzene core and endowed with a periphery of hexyloxy branches has been synthesized and is proposed as an active layer for organic light-emitting diodes processed by spin coating. In this work, we have obtained homogeneous thin films with blue emission (2.8 eV) by spin coating instead of the usual evaporation method used for low-weight molecular materials. The absorption and emission spectra of the films are analyzed and compared to that of the molecule. The obtained results show the dependence of the absorption and emission properties on the morphology and the dendrimer aggregation in the film. The effect of inter-dendrimer interactions leads to a broadening of the absorption bands and to a reduction of the threshold as the aggregation increases. The most efficient solid-state emission is for the films obtained from chloroform as solvent in the precursor solution.

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

Science.gov (United States)

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

2010-06-03

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

Dendrimers in drug research

DEFF Research Database (Denmark)

Boas, Ulrik; Heegaard, Peter M. H.

2004-01-01

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

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

Science.gov (United States)

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

2010-06-01

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

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

Science.gov (United States)

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

2009-08-06

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

Coherent exciton transport in dendrimers and continuous-time quantum walks

Science.gov (United States)

Mülken, Oliver; Bierbaum, Veronika; Blumen, Alexander

2006-03-01

We model coherent exciton transport in dendrimers by continuous-time quantum walks. For dendrimers up to the second generation the coherent transport shows perfect recurrences when the initial excitation starts at the central node. For larger dendrimers, the recurrence ceases to be perfect, a fact which resembles results for discrete quantum carpets. Moreover, depending on the initial excitation site, we find that the coherent transport to certain nodes of the dendrimer has a very low probability. When the initial excitation starts from the central node, the problem can be mapped onto a line which simplifies the computational effort. Furthermore, the long time average of the quantum mechanical transition probabilities between pairs of nodes shows characteristic patterns and allows us to classify the nodes into clusters with identical limiting probabilities. For the (space) average of the quantum mechanical probability to be still or to be again at the initial site, we obtain, based on the Cauchy-Schwarz inequality, a simple lower bound which depends only on the eigenvalue spectrum of the Hamiltonian.

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

Energy Technology Data Exchange (ETDEWEB)

Ciepluch, Karol, E-mail: ciepluch@biol.uni.lodz.pl [Department of General Biophysics, University of Lodz, 141/143 Pomorska St., 90-236 Lodz (Poland); Katir, Nadia [Laboratoire de Chimie de Coordination du CNRS (LCC), 205 route de Narbonne, F-31077 Toulouse cedex 4 (France); Institute of Nanomaterials and Nanotechnology (INANOTECH)-MAScIR (Moroccan Foundation for Advanced Science, Innovation and Research), ENSET, Avenue de l' Armee Royale, Madinat El Irfane, 10100 Rabat (Morocco); El Kadib, Abdelkrim [Institute of Nanomaterials and Nanotechnology (INANOTECH)-MAScIR (Moroccan Foundation for Advanced Science, Innovation and Research), ENSET, Avenue de l' Armee Royale, Madinat El Irfane, 10100 Rabat (Morocco); Weber, Monika [Department of General Biophysics, University of Lodz, 141/143 Pomorska St., 90-236 Lodz (Poland); Caminade, Anne-Marie [Laboratoire de Chimie de Coordination du CNRS (LCC), 205 route de Narbonne, F-31077 Toulouse cedex 4 (France); Bousmina, Mostapha [Hassan II Academy of Sciences and Technology, Avenue MVI, Km4, 10220 Rabat (Morocco); Pierre Majoral, Jean [Laboratoire de Chimie de Coordination du CNRS (LCC), 205 route de Narbonne, F-31077 Toulouse cedex 4 (France); Hassan II Academy of Sciences and Technology, Avenue MVI, Km4, 10220 Rabat (Morocco); Bryszewska, Maria [Department of General Biophysics, University of Lodz, 141/143 Pomorska St., 90-236 Lodz (Poland)

2012-06-15

This work deals with photo-physical and structural interactions between viologen phosphorus dendrimers and human serum albumin (HSA). Viologens are derivatives of 4,4 Prime -bipyridinium salts. Aiming to rationalize the parameters governing such interactions eight types of these polycationic dendrimers in which the generation, the number of charges, the nature of the core and of the terminal groups vary from one to another, were designed and used. The influence of viologen-based dendrimers' on human serum albumin has been investigated. The photo-physical interactions of the two systems have been monitored by fluorescence quenching of free L-tryptophan and of HSA tryptophan residue. Additionally, using circular dichroism (CD) the effect of dendrimers on the secondary structure of albumin was measured. The obtained results show that viologen dendrimers interact with human serum albumin quenching its fluorescence either by collisional (dynamic) way or by forming complexes in a ground state (static quenching). In some cases the quenching is accompanied by changes of the secondary structure of HSA. - Highlights: Black-Right-Pointing-Pointer Photo-physical interactions between viologen phosphorus dendrimers and human serum albumin (HSA) were investigated. Black-Right-Pointing-Pointer The viologen dendrimers can quench the fluorescence of tryptophan in HSA. Black-Right-Pointing-Pointer CD spectra to explain the changes in secondary structure of albumin after exposition of dendrimers.

Phosphorus dendrimers for nanomedicine.

Science.gov (United States)

Caminade, Anne-Marie

2017-08-31

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

Dendrimers: new hope for cancer

International Nuclear Information System (INIS)

Ghosh, S.S.

2010-01-01

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

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

Charge inversion of dendrimers in complexes with linear polyelectrolytes in the solutions with low pH

NARCIS (Netherlands)

Larin, S.V.; Lyulin, S.V.; Lyulin, A.V.; Darinskii, A.A.

2009-01-01

Complexes of fully ionized third-generation dendrimers with oppositely charged linear polyelectrolyte chains are studied by the Brownian dynamics method. A freely jointed model of a dendrimer and a linear chain is used. Electrostatic interactions are considered within the Debye-Hückel approximation

Induction of a robust immune response against avian influenza virus following transdermal inoculation with H5-DNA vaccine formulated in modified dendrimer-based delivery system in mouse model.

Science.gov (United States)

Bahadoran, Azadeh; Ebrahimi, Mehdi; Yeap, Swee Keong; Safi, Nikoo; Moeini, Hassan; Hair-Bejo, Mohd; Hussein, Mohd Zobir; Omar, Abdul Rahman

2017-01-01

This study was aimed to evaluate the immunogenicity of recombinant plasmid deoxyribonucleic acid (DNA), pBud-H5-green fluorescent protein (GFP)-interferon-regulatory factor (IRF)3 following delivery using polyamidoamine (PAMAM) dendrimer and transactivator of transcription (TAT)-conjugated PAMAM dendrimer as well as the effect of IRF3 as the genetic adjuvant. BALB/c mice were vaccinated transdermally with pBud-H5-GFP, PAMAM/pBud-H5-GFP, TAT-PAMAM/pBud-H5-GFP, and TAT-PAMAM/pBud-H5-GFP-IRF3. The expression analysis of H5 gene from the blood by using quantitative real-time reverse transcriptase polymerase chain reaction confirmed the ability of PAMAM dendrimer as a carrier for gene delivery, as well as the ability of TAT peptide to enhance the delivery efficiency of PAMAM dendrimer. Mice immunized with modified PAMAM by TAT peptide showed higher hemagglutination inhibition titer, and larger CD3 + /CD4 + T cells and CD3 + /CD8 + T cells population, as well as the production of cytokines, namely, interferon (IFN)-γ, interleukin (IL)-2, IL-15, IL-12, IL-6, and tumor necrosis factor-α compared with those immunized with native PAMAM. These results suggest that the function of TAT peptide as a cell-penetrating peptide is able to enhance the gene delivery, which results in rapid distribution of H5 in the tissues of the immunized mice. Furthermore, pBud-H5-GFP co-expressing IRF3 as a genetic adjuvant demonstrated the highest hemagglutination inhibition titer besides larger CD3 + /CD4 + and CD3 + /CD8 + T cells population, and strong Th1-like cytokine responses among all the systems tested. In conclusion, TAT-PAMAM dendrimer-based delivery system with IRF3 as a genetic adjuvant is an attractive transdermal DNA vaccine delivery system utilized to evaluate the efficacy of the developed DNA vaccine in inducing protection during challenge with virulent H5N1 virus.

Transepithelial Transport of PAMAM Dendrimers Across Isolated Human Intestinal Tissue.

Science.gov (United States)

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

2015-11-02

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

Chondrogenesis and hypertrophy in response to aggregate behaviors of human mesenchymal stem cells on a dendrimer-immobilized surface.

Science.gov (United States)

Wongin, Sopita; Ogawa, Yuuki; Kim, Mee-Hae; Viravaidya-Pasuwat, Kwanchanok; Kino-Oka, Masahiro

2017-08-01

To investigate the behaviors of aggregates of human mesenchymal stem cells (hMSCs) on chondrogenesis and chondrocyte hypertrophy using spatiotemporal expression patterns of chondrogenic (type II collagen) and hypertrophic (type X collagen) markers during chondrogenesis. hMSCs were cultured on either a polystyrene surface or polyamidoamine dendrimer surface with a fifth generation (G5) dendron structure in chondrogenic medium and growth medium. At day 7, cell aggregates without stress fibers formed on the G5 surface and triggered differentiation of hMSCs toward the chondrogenic fate, as indicated by type II collagen being observed while type X collagen was undetectable. In contrast, immunostaining of hMSCs cultured on polystyrene, which exhibited abundant stress fibers and did not form aggregates, revealed no evidence of either type II and or type X collagen. At day 21, the morphological changes of the cell aggregates formed on the G5 surface were suppressed as a result of stress fiber formation. Type II collagen was observed throughout the aggregates whereas type X collagen was detected only at the basal side of the aggregates. Change of cell aggregate behaviors derived from G5 surface alone regulated chondrogenesis and hypotrophy, and this was enhanced by chondrogenic medium. Incubation of hMSCs affects the expression of type II and X collagens via effects on cell aggregate behavior and stress fiber formation.

Research progress on synthesis and characteristic about dendrimers

Science.gov (United States)

Tang, Zitao

2017-12-01

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

Pharmaceutical and biomedical potential of surface engineered dendrimers.

Science.gov (United States)

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

2007-01-01

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

Viologen-Phosphorus Dendrimers Inhibit α-Synuclein Fibrillation.

Science.gov (United States)

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

2013-03-04

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

Targeting human liver cancer cells with lactobionic acid-G(4)-PAMAM-FITC sorafenib loaded dendrimers.

Science.gov (United States)

Iacobazzi, Rosa Maria; Porcelli, Letizia; Lopedota, Angela Assunta; Laquintana, Valentino; Lopalco, Antonio; Cutrignelli, Annalisa; Altamura, Emiliano; Di Fonte, Roberta; Azzariti, Amalia; Franco, Massimo; Denora, Nunzio

2017-08-07

Reported here is the synthesis and biological evaluation of the asialoglycoprotein receptor (ASGP-R) targeted fourth generation poliamidoamine dendrimer (G(4)-PAMAM) loaded with sorafenib. The ASGP-R targeted dendrimer was obtained by conjugation of Lactobionic acid (La) to the G(4)-PAMAM dendrimer, followed by acetylation (Ac) of the free amino groups in order to reduce the non-specific interactions with the cell membrane. Moreover, by additionally grafting fluorescein (FITC), it was easy to characterize the internalization pathway and the intracellular fate of the targeted dendrimer Ac-La-G(4)-PAMAM-FITC. In vitro experiments performed on HepG-2 and HLE cell lines, allowed to study the ability of the dendrimers to affect the cell vitality. Confocal microscopy and cytofluorimetric analysis confirmed higher binding and uptake ability of the Ac-La-G(4)-PAMAM-FITC dendrimer in well differentiated and ASGP-R expressing human liver cancer cell line HepG-2 compared non-expressing HLE cells. Ac-La-G(4)-PAMAM-FITC dendrimer loaded with sorafenib was stable and showed sustained sorafenib release. As evidenced by the cytotoxicity studies, sorafenib included in the dendrimer maintained its effectiveness, and was able to produce a longer lasting effect over the time compared to molar equivalent doses of free sorafenib. This new targeted dendrimer appears to be a suitable carrier for the delivery of sorafenib to liver cancer cells expressing ASGP-R. Copyright © 2017 Elsevier B.V. All rights reserved.

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

International Nuclear Information System (INIS)

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

2005-01-01

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

Hyperbranched–dendrimer architectural copolymer gene delivery using hyperbranched PEI conjugated to poly(propyleneimine) dendrimers: synthesis, characterization, and evaluation of transfection efficiency

Energy Technology Data Exchange (ETDEWEB)

Alavi, Seyyed Jamal [Ferdowsi University of Mashhad, Department of Chemistry, Faculty of Science (Iran, Islamic Republic of); Gholami, Leila [Mashhad University of Medical Sciences, Department of Modern Sciences and Technologies, School of Medicine (Iran, Islamic Republic of); Askarian, Saeedeh [Mashhad University of Medical Sciences, Department of Medical Biotechnology, School of Medicine (Iran, Islamic Republic of); Darroudi, Majid [Mashhad University of Medical Sciences, Nuclear Medicine Research Center (Iran, Islamic Republic of); Massoudi, Abdolhossein [University of Payam noor, Department of Chemistry (Iran, Islamic Republic of); Rezaee, Mehdi; Kazemi Oskuee, Reza, E-mail: Oskueekr@mums.ac.ir [Mashhad University of Medical Sciences, Department of Medical Biotechnology, School of Medicine (Iran, Islamic Republic of)

2017-02-15

The applications of dendrimer-based vectors seem to be promising in non-viral gene delivery because of their potential for addressing the problems with viral vectors. In this study, generation 3 poly(propyleneimine) (G3-PPI) dendrimers with 1, 4-diaminobutane as a core initiator was synthesized using a divergent growth approach. To increase the hydrophobicity and reduce toxicity, 10% of primary amines of G3-PPI dendrimers were replaced with bromoalkylcarboxylates with different chain lengths (6-bromohexanoic and 10-bromodecanoic). Then, to retain the overall buffering capacity and enhance transfection, the alkylcarboxylate–PPIs were conjugated to 10 kDa branched polyethylenimine (PEI). The results showed that the modified PPI was able to form complexes with the diameter of less than 60 nm with net-positive surface charge around 20 mV. No significant toxicity was observed in modified PPIs; however, the hexanoate conjugated PPI–PEI (PPI-HEX-10% PEI) and the decanoate conjugated PPI–PEI (PPI-DEC-10%-PEI) showed the best transfection efficiency in murine neuroblastoma (Neuro-2a) cell line, even PPI-HEX-10%-PEI showed transfection efficiency equal to standard PEI 25 kDa with reduced toxicity. This study suggested a new series of hyperbranched (PEI)–dendrimer (PPI) architectural copolymers as non-viral gene delivery vectors with high transfection efficiency and low toxicity.

Hyperbranched-dendrimer architectural copolymer gene delivery using hyperbranched PEI conjugated to poly(propyleneimine) dendrimers: synthesis, characterization, and evaluation of transfection efficiency

Science.gov (United States)

Alavi, Seyyed Jamal; Gholami, Leila; Askarian, Saeedeh; Darroudi, Majid; Massoudi, Abdolhossein; Rezaee, Mehdi; Kazemi Oskuee, Reza

2017-02-01

The applications of dendrimer-based vectors seem to be promising in non-viral gene delivery because of their potential for addressing the problems with viral vectors. In this study, generation 3 poly(propyleneimine) (G3-PPI) dendrimers with 1, 4-diaminobutane as a core initiator was synthesized using a divergent growth approach. To increase the hydrophobicity and reduce toxicity, 10% of primary amines of G3-PPI dendrimers were replaced with bromoalkylcarboxylates with different chain lengths (6-bromohexanoic and 10-bromodecanoic). Then, to retain the overall buffering capacity and enhance transfection, the alkylcarboxylate-PPIs were conjugated to 10 kDa branched polyethylenimine (PEI). The results showed that the modified PPI was able to form complexes with the diameter of less than 60 nm with net-positive surface charge around 20 mV. No significant toxicity was observed in modified PPIs; however, the hexanoate conjugated PPI-PEI (PPI-HEX-10% PEI) and the decanoate conjugated PPI-PEI (PPI-DEC-10%-PEI) showed the best transfection efficiency in murine neuroblastoma (Neuro-2a) cell line, even PPI-HEX-10%-PEI showed transfection efficiency equal to standard PEI 25 kDa with reduced toxicity. This study suggested a new series of hyperbranched (PEI)-dendrimer (PPI) architectural copolymers as non-viral gene delivery vectors with high transfection efficiency and low toxicity.

Second-Order Nonlinear Optical Dendrimers and Dendronized Hyperbranched Polymers.

Science.gov (United States)

Tang, Runli; Li, Zhen

2017-01-01

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

Perspective: Dendrimer drugs for infection and inflammation.

Science.gov (United States)

Shaunak, Sunil

2015-12-18

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

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

DEFF Research Database (Denmark)

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

2007-01-01

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

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

International Nuclear Information System (INIS)

Orocio R, E.

2013-01-01

The objective of this project was preparing a multimeric system through the conjugation of several molecules of the peptide Tyr 3 -Octreotide to a dendrimer molecule based on Poly-amidoamine (PAMAM), as well as radiolabeled with 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 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 99m Tc was carried out using a direct method that involves the reduction of the anion TcO 4 - 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 99m Tc-PAMAM-Tyr 3 -Octreotide is excreted by via renal as hepatobiliary

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

Science.gov (United States)

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

2017-06-01

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

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.

Preparation of Cu Nanoclusters within Dendrimer Templates

National Research Council Canada - National Science Library

Zhao, M

1998-01-01

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

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

Science.gov (United States)

Masrour, R.; Jabar, A.

2016-11-01

We investigate the magnetic properties of Cayley trees of large molecules with dendrimer structure using Monte Carlo simulations. The thermal magnetization and magnetic susceptibility of a dendrimer structure are given with different coordination numbers, Z=3, 4, 5 and different generations g=3 and 2. The variation of magnetizations with the exchange interactions and crystal fields have been given of this system. The magnetic hysteresis cycles have been established.

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.

Noncovalent synthesis of protein dendrimers

NARCIS (Netherlands)

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

2009-01-01

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