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Sample records for end-grafted carbosilane dendrimers

  1. Carbosilane and Carbosiloxane Dendrimers

    Directory of Open Access Journals (Sweden)

    Jang Hwan Hong

    2009-09-01

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

  2. Carbosilane dendrimers affect the fibrillation of α-synuclein

    Science.gov (United States)

    Milowska, Katarzyna; Gomez-Ramirez, Rafael; de la Mata, Francisco Javier; Gabryelak, Teresa; Bryszewska, Maria

    2015-12-01

    Participation of α-synuclein (ASN) in the pathogenesis of Parkinson's disease is undeniable. This protein is important for functioning of neurons. Conformational changes in ASN and its aggregation result in neurodegeneration. Therefore, the factors preventing aggregation need to be identified. The search for the potential agents preventing fibrillation of proteins in neurodegenerative diseases has also involved polymers such as dendrimers. The aim of this study was to examine the role of carbosilane dendrimers (CBS) in α-synuclein fibrillation process and to assess the structural changes in α-synuclein under the influence of dendrimers. ASN interactions with carbosilane dendrimers were examined by measuring the zeta potential. The fibrillation and structural changes were examined using CD spectroscopy. The results obtained in this study suggest that carbosilane dendrimers can be potential inhibitors of ASN fibril formation. The fact that dendrimers can prevent ASN fibrillation in suspension is important for further research because it may lead to the design of effective pharmacological strategies.

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

    Science.gov (United States)

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

    2016-01-01

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

  4. Carbosilane dendrimers inhibit α-synuclein fibrillation and prevent cells from rotenone-induced damage.

    Science.gov (United States)

    Milowska, Katarzyna; Szwed, Aleksandra; Mutrynowska, Marta; Gomez-Ramirez, Rafael; de la Mata, Francisco Javier; Gabryelak, Teresa; Bryszewska, Maria

    2015-04-30

    This study investigates the role of carbosilane dendrimers in fibrillation of α-synuclein and prevention of the mouse hippocampal cell (mHippoE-18) from rotenone-induced damage. Examining the interaction between carbosilane dendrimers and α-synuclein, we found that the dendrimers inhibit fibril formation. We also investigated cell viability, the production of reactive oxygen species (ROS), and mitochondrial membrane potential. mHippoE-18 cells were preincubated with carbosilane dendrimers before rotenone was added. All the dendrimers possess potential protection activity. Preincubation with dendrimers contributed to: increased viability, higher mitochondrial membrane potential, and reduced ROS level in cells. The probable mechanism of cell protection lies in the ability of dendrimers to capture rotenone by encapsulating or binding to its surface groups. The fact that dendrimers have prevention potential is important in the search for new pharmacological strategies against neurodegenerative disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Sialyl alpha(2-->3) lactose clusters using carbosilane dendrimer core scaffolds as influenza hemagglutinin blockers.

    Science.gov (United States)

    Oka, Hiroyuki; Onaga, Tomotsune; Koyama, Tetsuo; Guo, Chao-Tan; Suzuki, Yasuo; Esumi, Yasuaki; Hatano, Ken; Terunuma, Daiyo; Matsuoka, Koji

    2008-08-01

    An efficient synthesis of a series of carbosilane dendrimers uniformly functionalized with sialyl alpha(2-->3) lactose (Neu5Acalpha(2-->3)Galbeta(1-->4)Glcbeta1-->) moieties was accomplished. The results of a preliminary study on biological responses against influenza virus hemagglutinin, using the sialyl lactose clusters showed unique biological activities on the basis of the structure-activity relationship according to the carbosilane scaffolds.

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

    Science.gov (United States)

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

    2016-09-01

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

  7. Synthesis of polyaryl rigid-core carbosilane dendrimers for supported organic synthesis

    NARCIS (Netherlands)

    Wander, M.; Hausoul, P.J.C.; Sliedregt, L.A.J.M.; van Steen, B.J.; van Koten, G.; Klein Gebbink, R.J.M.

    2009-01-01

    Carbosilane dendrimers can be used as soluble supports for organic synthesis, since their structure allows separation of excess reagents from the supported products, eventually yielding products of high purity and in high yield, as in solid-phase organic synthesis (SPOS). In previous studies often

  8. Carbosilane dendrimers as gene delivery agents for the treatment of HIV infection.

    Science.gov (United States)

    Perisé-Barrios, Ana Judith; Jiménez, José Luis; Domínguez-Soto, Angeles; de la Mata, F Javier; Corbí, Angel L; Gomez, Rafael; Muñoz-Fernandez, María Ángeles

    2014-06-28

    Despite the use of siRNA in the downregulation of HIV-1 replication which has been reported, CD4 T lymphocytes are difficult to transfect with non-viral vectors. We determined whether second generation carbosilane dendrimers (2G-NN16 and 2G-03NN24) may be efficient transfectants in CD4 T lymphocytes. Dendrimers were also tested on macrophages to determine whether they can modify macrophage phenotype and induce an inflammatory response. The nanoconjugate formed by 2G-03NN24/siRNA-Nef presents the highest inhibition of HIV-1 replication. Dendrimers presented safety properties because they did not induce proliferation on CD4 T lymphocytes and decrease the release of TNFα and IL-12p40 by macrophages. Both dendrimers also decrease the phagocytosis activity. Additionally, 2G-03NN24 dendrimer decreases the CCL2 and CCR2 expression in macrophages. Carbosilane dendrimers 2G-NN16 and 2G-03NN24 can be used as efficient non-viral vectors for gene therapy applications, mainly in the treatment of HIV infection. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-10-15

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

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

    Science.gov (United States)

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

    2015-02-01

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

  11. Anti-Human Immunodeficiency Virus Activity of Thiol-Ene Carbosilane Dendrimers and Their Potential Development as a Topical Microbicide.

    Science.gov (United States)

    Sánchez-Rodríguez, Javier; Díaz, Laura; Galán, Marta; Maly, Marek; Gómez, Rafael; Javier de la Mata, F; Jiménez, José L; Muñoz-Fernández, M Angeles

    2015-10-01

    The concept of a "microbicide" was born out of the lack of a vaccine against HIV and the difficulty of women in ensuring the use of preventive prophylaxis by their partners, especially in developing countries. Approaches using polyanionic carbosilane dendrimers have shown promise in the development of new microbicides. We have developed and evaluated two anionic carbosilane dendrimers with sulfonate and carboxylate terminal groups, G2-STE16 and G2-CTE16. Both dendrimers showed high biosafety in human epithelial cell lines derived from the vagina and in primary blood human cells (PBMCs). The dendrimers not only have a greater capacity to block the entry of different X4- and R5-HIV-1 isolates into epithelial cells but also prevent the HIV-1 infection of activated PBMCs. The treatment of epithelial cells with different carbosilane dendrimers did not produce changes in the activation or proliferation of PBMCs or in the expression of CD4, CCR5 or CXCR4. Computational modeling showed significantly higher affinities for the complexes G2-STE16/gp120 and G2-CTE16/gp120. Moreover, no irritation or vaginal lesions were detected in female BALB/c mice after vaginal administration of the dendrimers. Summing up, G2-STE16 and G2-CTE16 are easy to synthesize and compatible with functional groups, and the purification steps are easy and short. Our results have clearly demonstrated that these dendrimers have high potency as a topical microbicide against HIV-1 infection.

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

    Science.gov (United States)

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

    2015-02-01

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

  13. Thermodynamic properties of first- and third-generation carbosilane dendrimers with terminal phenyldioxolane groups

    Science.gov (United States)

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

    2017-12-01

    The heat capacities of first- and third-generation carbosilane dendrimers with terminal phenyldioxolane groups are studied as a function of temperature via vacuum and differential scanning calorimetry in the range of 6 to 520 K. Physical transformations that occur in the above temperature range are detected and their standard thermodynamic characteristics are determined and analyzed. Standard thermodynamic functions C p ο( T), [ H°( T) - H°(0)], [ S°( T) - S°(0)], and [ G°( T) - H°(0)] in the temperature range of T → 0 to 520 K for different physical states and the standard entropies of formation of the studied dendrimers at T = 298.15 K are calculated, based on the obtained experimental data.

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

    Science.gov (United States)

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

    2014-01-01

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

  15. Development of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides

    Science.gov (United States)

    Briz, Verónica; Sepúlveda-Crespo, Daniel; Diniz, Ana Rita; Borrego, Pedro; Rodes, Berta; de La Mata, Francisco Javier; Gómez, Rafael; Taveira, Nuno; Muñoz-Fernández, Mª Ángeles

    2015-08-01

    The development of topical microbicide formulations for vaginal delivery to prevent HIV-2 sexual transmission is urgently needed. Second- and third-generation polyanionic carbosilane dendrimers with a silicon atom core and 16 sulfonate (G2-S16), napthylsulfonate (G2-NS16) and sulphate (G3-Sh16) end-groups have shown potent and broad-spectrum anti-HIV-1 activity. However, their antiviral activity against HIV-2 and mode of action have not been probed. Cytotoxicity, anti-HIV-2, anti-sperm and antimicrobial activities of dendrimers were determined. Analysis of combined effects of triple combinations with tenofovir and raltegravir was performed by using CalcuSyn software. We also assessed the mode of antiviral action on the inhibition of HIV-2 infection through a panel of different in vitro antiviral assays: attachment, internalization in PBMCs, inactivation and cell-based fusion. Vaginal irritation and histological analysis in female BALB/c mice were evaluated. Our results suggest that G2-S16, G2-NS16 and G3-Sh16 exert anti-HIV-2 activity at an early stage of viral replication inactivating the virus, inhibiting cell-to-cell HIV-2 transmission, and blocking the binding of gp120 to CD4, and the HIV-2 entry. Triple combinations with tenofovir and raltegravir increased the anti-HIV-2 activity, consistent with synergistic interactions (CIwt: 0.33-0.66). No vaginal irritation was detected in BALB/c mice after two consecutive applications for 2 days with 3% G2-S16. Our results have clearly shown that G2-S16, G2-NS16 and G3-Sh16 have high potency against HIV-2 infection. The modes of action confirm their multifactorial and non-specific ability, suggesting that these dendrimers deserve further studies as potential candidate microbicides to prevent vaginal/rectal HIV-1/HIV-2 transmission in humans.

  16. Syntheses and biological evaluations of carbosilane dendrimers uniformly functionalized with sialyl alpha(2-->3) lactose moieties as inhibitors for human influenza viruses.

    Science.gov (United States)

    Oka, Hiroyuki; Onaga, Tomotsune; Koyama, Tetsuo; Guo, Chao-Tan; Suzuki, Yasuo; Esumi, Yasuaki; Hatano, Ken; Terunuma, Daiyo; Matsuoka, Koji

    2009-08-01

    A series of carbosilane dendrimers uniformly functionalized with sialyl lactose moieties (Neu5Ac alpha2-->3Gal beta1-->4Glc) was systematically synthesized, and biological evaluations for anti-influenza virus activity using the glycodendrimers were performed. The results suggested that the glycodendrimers had unique biological activities depending on the form of their core frame, and Dumbbell(1)6-amide type glycodendrimer 7 showed particularly strong inhibitory activities against human influenza viruses [A/PR/8/34 (H1N1) and A/Aichi/2/68 (H3N2)]. The results suggested that the structure-activity relationship (SAR) on the glycolibrary against various influenza viruses was observed, and dumbbell-shaped dendrimers as supporting carbohydrate moieties were found to be the most suitable core scaffolds in this study.

  17. Characterization by Fourier transform infrared spectroscopy (FT-IR) and 2D IR correlation spectroscopy of a carbosilane dendrimer with peripheral ammonium groups

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-06-15

    Fourier transform infrared spectroscopy and 2D correlation spectroscopy were used to study the microstructural changes occurring on heating of a new carbosilane dendrimer with peripheral ammonium groups. Temperature-dependent spectral variations in the 3,010-2,710, 1,530-1,170, and 1,170-625 cm{sup -1} regions were monitored during the heating process. The dependence, on temperature, of integral absorptions and position of spectral bands was established and the spectral modifications associated with molecular conformation rearrangements, allowing molecular shape changes, were found. Before 180 Degree-Sign C, the studied carbosilane dendrimer proved to be stable, while at higher temperatures it oxidizes and Si-O groups appear. 2D IR correlation spectroscopy gives new information about the effect of temperature on the structure and dynamics of the system. Synchronous and asynchronous spectra indicate that, at low temperature, conformational changes of CH{sub 3} and CH{sub 3}-N{sup +} groups take place first. With increasing temperature, the intensity variation of the CH{sub 2}, C-N, Si-C and C-C groups from the dendritic core is faster than that of the terminal units. This indicates that, with increasing temperature, the segments of the dendritic core obtain enough energy to change their conformation more easily as compared to the terminal units, due to their internal flexibility.

  18. 'Dialyzable' Carbosilane Dendrimers as Soluble Supports in Organic Synthesis: Proof of principle, application and diafiltration performance

    NARCIS (Netherlands)

    Wander, M.

    2012-01-01

    Since the development of polystyrene as (insoluble) support for the synthesis of peptides by Merrifield in the 1960s, the application of supported synthesis in both industrial and academic research has increased. The introduction of dendrimers as supports solved many of the problems arising from the

  19. Synthesis of Periphery Functionalized Dendritic Molecules using Polylithiated Dendrimers as Starting Material

    NARCIS (Netherlands)

    Koten, G. van; Wijkens, P.; Jastrzebski, J.T.B.H.; Schaaf, P.A. van der; Kolly, R.; Hafner, A.

    2000-01-01

    A general method for the functionalization of Si-Cl terminated carbosilane dendritic molecules via organolithium or organomagnesium reagents is described. Quantitative exchange of the bromine atoms of 4-bromophenyl-functionalized dendrimers affords polylithiated species that are valuable starting

  20. Organoclays with Carbosilane Dendrimers Containing Ammonium or Phosphonium Groups.

    Czech Academy of Sciences Publication Activity Database

    Müllerová, Monika; Šabata, Stanislav; Matoušek, J.; Kormunda, M.; Holubová, J.; Bálková, R.; Petričkovič, Roman; Koštejn, M.; Kupčík, Jaroslav; Fajgar, Radek; Strašák, Tomáš

    2018-01-01

    Roč. 42, č. 2 (2018), s. 1187-1196 ISSN 1144-0546 Institutional support: RVO:67985858 Keywords : organic-inorganic nanocomposites * layered silicates * thermal-stability Subject RIV: CC - Organic Chemistry Impact factor: 3.269, year: 2016

  1. Synthesis of periphery-functionalized dendritic molecules using polylithiated dendrimers as starting material

    Science.gov (United States)

    Wijkens; Jastrzebski; van Der Schaaf PA; Kolly; Hafner; van Koten G

    2000-06-01

    A general method for the functionalization of Si-Cl terminated carbosilane dendritic molecules via organolithium or organomagnesium reagents is described. Quantitative exchange of the bromine atoms of 4-bromophenyl-functionalized dendrimers affords polylithiated species that are valuable starting materials for further functionalization, e.g., into pyridyl alcohols. The latter were successfully applied as catalyst precursors in a ruthenium-mediated ring-closure metathesis reaction.

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

    Science.gov (United States)

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

    2016-04-07

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

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

    Science.gov (United States)

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

    2016-04-01

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

  4. Dendrimer Prodrugs

    Directory of Open Access Journals (Sweden)

    Soraya da Silva Santos

    2016-05-01

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

  5. Special Issue: "Functional Dendrimers".

    Science.gov (United States)

    Tomalia, Donald A

    2016-08-09

    This special issue entitled "Functional Dendrimers" focuses on the manipulation of at least six "critical nanoscale design parameters" (CNDPs) of dendrimers including: size, shape, surface chemistry, flexibility/rigidity, architecture and elemental composition. These CNDPs collectively define properties of all "functional dendrimers". This special issue contains many interesting examples describing the manipulation of certain dendrimer CNDPs to create new emerging properties and, in some cases, predictive nanoperiodic property patterns (i.e., dendritic effects). The systematic engineering of CNDPs provides a valuable strategy for optimizing functional dendrimer properties for use in specific applications.

  6. 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

  7. Dendrimers in drug research

    DEFF Research Database (Denmark)

    Boas, Ulrik; Heegaard, Peter M. H.

    2004-01-01

    are the use of dendrimers as 'glycocarriers' for the controlled multimeric presentation of biologically relevant carbohydrate moieties which are useful for targeting modified tissue in malignant diseases for diagnostic and therapeutic purposes. Finally, the use of specific types of dendrimers as scaffolds...

  8. Dendrimers in Medicine

    DEFF Research Database (Denmark)

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

    2015-01-01

    Dendrimers are three-dimensional macromolecular structures originating from a central core molecule and surrounded by successive addition of branching layers (generation). These structures exhibit a high degree of molecular uniformity, narrow molecular weight distribution, tunable size and shape ...... as challenging issues surrounding the future development of dendrimer-based medicines....

  9. Born energy, acid-base equilibrium, structure and interactions of end-grafted weak polyelectrolyte layers

    Science.gov (United States)

    Nap, R. J.; Tagliazucchi, M.; Szleifer, I.

    2014-01-01

    This work addresses the effect of the Born self-energy contribution in the modeling of the structural and thermodynamical properties of weak polyelectrolytes confined to planar and curved surfaces. The theoretical framework is based on a theory that explicitly includes the conformations, size, shape, and charge distribution of all molecular species and considers the acid-base equilibrium of the weak polyelectrolyte. Namely, the degree of charge in the polymers is not imposed but it is a local varying property that results from the minimization of the total free energy. Inclusion of the dielectric properties of the polyelectrolyte is important as the environment of a polymer layer is very different from that in the adjacent aqueous solution. The main effect of the Born energy contribution on the molecular organization of an end-grafted weak polyacid layer is uncharging the weak acid (or basic) groups and consequently decreasing the concentration of mobile ions within the layer. The magnitude of the effect increases with polymer density and, in the case of the average degree of charge, it is qualitatively equivalent to a small shift in the equilibrium constant for the acid-base equilibrium of the weak polyelectrolyte monomers. The degree of charge is established by the competition between electrostatic interactions, the polymer conformational entropy, the excluded volume interactions, the translational entropy of the counterions and the acid-base chemical equilibrium. Consideration of the Born energy introduces an additional energetic penalty to the presence of charged groups in the polyelectrolyte layer, whose effect is mitigated by down-regulating the amount of charge, i.e., by shifting the local-acid base equilibrium towards its uncharged state. Shifting of the local acid-base equilibrium and its effect on the properties of the polyelectrolyte layer, without considering the Born energy, have been theoretically predicted previously. Account of the Born energy leads

  10. Born energy, acid-base equilibrium, structure and interactions of end-grafted weak polyelectrolyte layers.

    Science.gov (United States)

    Nap, R J; Tagliazucchi, M; Szleifer, I

    2014-01-14

    This work addresses the effect of the Born self-energy contribution in the modeling of the structural and thermodynamical properties of weak polyelectrolytes confined to planar and curved surfaces. The theoretical framework is based on a theory that explicitly includes the conformations, size, shape, and charge distribution of all molecular species and considers the acid-base equilibrium of the weak polyelectrolyte. Namely, the degree of charge in the polymers is not imposed but it is a local varying property that results from the minimization of the total free energy. Inclusion of the dielectric properties of the polyelectrolyte is important as the environment of a polymer layer is very different from that in the adjacent aqueous solution. The main effect of the Born energy contribution on the molecular organization of an end-grafted weak polyacid layer is uncharging the weak acid (or basic) groups and consequently decreasing the concentration of mobile ions within the layer. The magnitude of the effect increases with polymer density and, in the case of the average degree of charge, it is qualitatively equivalent to a small shift in the equilibrium constant for the acid-base equilibrium of the weak polyelectrolyte monomers. The degree of charge is established by the competition between electrostatic interactions, the polymer conformational entropy, the excluded volume interactions, the translational entropy of the counterions and the acid-base chemical equilibrium. Consideration of the Born energy introduces an additional energetic penalty to the presence of charged groups in the polyelectrolyte layer, whose effect is mitigated by down-regulating the amount of charge, i.e., by shifting the local-acid base equilibrium towards its uncharged state. Shifting of the local acid-base equilibrium and its effect on the properties of the polyelectrolyte layer, without considering the Born energy, have been theoretically predicted previously. Account of the Born energy leads

  11. STM investigation on single, physisorbed dendrimers

    NARCIS (Netherlands)

    Merz, L.; Hitz, J.; Hubler, U.; Weyermann, P.; Diederich, F.; Murer, P.; Seebach, D.; Widmer, I.; Stöhr, Meike; Güntherodt, H.-J.; Hermann, B.A.

    2002-01-01

    Porphyrin dendrimers were synthesized to mimic naturally occurring proteins, which catalyze a number of biochemically important reactions. In addition, chiral dendrimers were prepared as model compounds for the study of nanoscopic chirality. The structures of these dendrimers cannot be characterized

  12. 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.

  13. 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...

  14. Peptide-functionalized polyphenylene dendrimers

    NARCIS (Netherlands)

    Herrmann, Andreas; Mihov, Gueorgui; Vandermeulen, Guido W.M.; Klok, Harm-Anton; Müllen, Klaus

    2003-01-01

    This contribution describes the synthesis of polyphenylene dendrimers that are functionalized with up to 16 lysine residues or substituted with short peptide sequences composed of 5 lysine or glutamic acid repeats and a C- or N-terminal cysteine residue. Polyphenylene dendrimers were prepared via a

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-04-15

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

  16. Polyester Dendrimers: Smart Carriers for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Jean–d’Amour K. Twibanire

    2014-01-01

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

  17. [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.

  18. Dendrimers and their Applications: A Review Article

    Directory of Open Access Journals (Sweden)

    Mughisa Munir

    2016-01-01

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

  19. Influence of dendrimers on red blood cells.

    Science.gov (United States)

    Ziemba, Barbara; Matuszko, Gabriela; Bryszewska, Maria; Klajnert, Barbara

    2012-03-01

    Dendrimers, highly branched macromolecules with a specific size and shape, provide many exciting opportunities for biomedical applications. However, most dendrimers demonstrate toxic and haemolytic activity because of their positively charged surface. Masking the peripheral cationic groups by coating them with biocompatible molecules is a method to reduce it. It was proven that modified dendrimers can even diminish haemolytic activity of encapsulated drugs. Experiments confirmed that anionic dendrimers are less haemotoxic than cationic ones. Due to the high affinity of dendrimers for serum proteins, presence of these components in an incubation buffer might also influence red blood cell (RBC)-dendrimer interactions and decrease the haemolysis level. Generally, haemotoxicity of dendrimers is concentration-, generation-, and time-dependent. Various changes in the RBCs' shape in response to interactions with dendrimers have been observed, from echinocytic transformations through cell aggregation to cluster formation, depending on the dendrimer's type and concentration. Understanding the physical and chemical origins of dendrimers' influences on RBCs might advance scientists' ability to construct dendrimers more suitable for medical applications.

  20. Fluorescence and Intramolecular Energy Transfer in Polyphenylene Dendrimers

    NARCIS (Netherlands)

    Liu, Daojun; Feyter, Steven De; Cotlet, Mircea; Stefan, Alina; Wiesler, Uwe-Martin; Herrmann, Andreas; Grebel-Koehler, Dörthe; Qu, Jianqiang; Müllen, Klaus; Schryver, Frans C. De

    2003-01-01

    The fluorescence of polyphenylene dendrimers and the intramolecular energy transfer in polyphenylene dendrimers containing a perylenediimide core have been investigated in this paper. Polyphenylene dendrimers composed of tens or hundreds of out-of-plane twisted phenyl units exhibit strong

  1. Structure of asymmetrical peptide dendrimers

    NARCIS (Netherlands)

    Okrugin, B.M.; Neelov, I.M.; Leermakers, F.A.M.; Borisov, Oleg V.

    2017-01-01

    Structural properties of asymmetric peptide dendrimers up to the 11th generation are studied on the basis of the self-consistent field Scheutjens-Fleer numerical approach. It is demonstrated that large scale properties such as, e.g., the gyration radius, are relatively weakly affected by the

  2. Synthesis, characterization and antibacterial behavior of water-soluble carbosilane dendrons containing ferrocene at the focal point.

    Science.gov (United States)

    Lozano-Cruz, Tania; Ortega, Paula; Batanero, Belen; Copa-Patiño, Jose Luis; Soliveri, Juan; de la Mata, Fco Javier; Gómez, Rafael

    2015-11-28

    A series of novel water-soluble ammonium-terminated carbosilane dendrons containing a ferrocene unit at the focal point were synthesized, in order to combine the unique redox activity of ferrocene and the precisely designed structure of the dendrons with the aim to evaluate them as a new class of potential organometallic-based antibacterial compounds. The synthetic route is based on the initial amination of ferrocenecarboxaldehyde with carbosilane dendrons that contain allyl groups on the surface followed by reduction of the in situ prepared imine product, and the subsequent functionalization of the periphery with terminal amine groups by hydrosilylation reactions. Systems quaternized with HCl are soluble and stable in water or other protic solvents. The obtained compounds were spectrally and electrochemically (cyclic voltammetry) characterized, and diffusion-ordered spectroscopy experiments were conducted to determine the size of the dendritic wedges in solution. The antibacterial activity of these compounds was evaluated using Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli), which shows that the first and second generations of cationic dendrons are broad spectrum antibacterial agents, i.e. selective and effective in both bacterial strains.

  3. Dendrimers as Innovative Radiopharmaceuticals in Cancer Radionanotherapy.

    Science.gov (United States)

    Liko, Flonja; Hindré, François; Fernandez-Megia, Eduardo

    2016-10-10

    Radiotherapy is one of the most commonly used cancer treatments, with an estimate of 40% success that could be improved further if more efficient targeting and retention of radiation at the tumor site were achieved. This review focuses on the use of dendrimers in radionanotherapy, an emerging technology aimed to improve the efficiency of radiotherapy by implementing nanovectorization, an already established praxis in drug delivery and diagnosis. The labeling of dendrimers with radionuclides also aims to reduce the dose of radiolabeled materials and, hence, their toxicity and tumor resistance. Examples of radiolabeled dendrimers with alpha, beta, and Auger electron emitters are commented, along with the use of dendrimers in boron neutron capture therapy (BNCT). The conjugation of radiolabeled dendrimers to monoclonal antibodies for a more efficient targeting and the application of dendrimers in gene delivery radiotherapy are also covered.

  4. Genotoxicity of poly(propylene imine) dendrimers.

    Science.gov (United States)

    Ziemba, Barbara; Matuszko, Gabriela; Appelhans, Dietmar; Voit, Brigitte; Bryszewska, Maria; Klajnert, Barbara

    2012-08-01

    Dendrimers are highly branched macromolecules with the potential in biomedical applications. Due to positively charged surfaces, several dendrimers reveal toxicity. Coating peripheral cationic groups with carbohydrate residues can reduce it. In this study, the cytotoxicity and genotoxicity of three types of 4th generation poly(propylene imine) dendrimers were investigated. Peripheral blood mononuclear cells (PBMCs) were treated with uncoated (PPI-g4) dendrimers, and dendrimers in which approximately 40% or 90% of peripheral amino groups were coated with maltotriose (PPI-g4-OS or PPI-g4-DS) at concentration of 0.05, 0.5, 5 mg/ml. Abbreviations OS and DS stand for open shell and dense shell respectively, that describes the structure of carbohydrate modified dendrimers. After 1 h of cell incubation at 37°C, the MTT and comet assays were performed. PPI dendrimers demonstrated surface-modification-degree dependent toxicity, although genotoxicity of PPI-g4 and PPI-g4-OS measured by the comet assay was concentration dependent up to 0.5 mg/ml and at 5 mg/ml the amount of DNA that left comet's head decreased. Results may suggest a strong interaction between dendrimers and DNA, and furthermore, that coating PPI dendrimers by maltoriose is an efficient method to reduce their genotoxicity what opens the possibilities to use them as therapeutic agents or drug carriers. Copyright © 2012 Wiley Periodicals, Inc.

  5. High Fluorescent Porphyrin-PAMAM-Fluorene Dendrimers.

    Science.gov (United States)

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

    2015-05-13

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

  6. Stimuli-responsive dendrimers in drug delivery.

    Science.gov (United States)

    Wang, Hui; Huang, Quan; Chang, Hong; Xiao, Jianru; Cheng, Yiyun

    2016-03-01

    Dendrimers have shown great promise as carriers in drug delivery due to their unique structures and superior properties. However, the precise control of payload release from a dendrimer matrix still presents a great challenge. Stimuli-responsive dendrimers that release payloads in response to a specific trigger could offer distinct clinical advantages over those dendrimers that release payloads passively. These smart polymers are designed to specifically release their payloads at targeted regions or at constant release profiles for specific therapies. They represent an attractive alternative to targeted dendrimers and enable dendrimer-based therapeutics to be more effective, more convenient, and much safer. The wide range of stimuli, either endogenous (acid, enzyme, and redox potentials) or exogenous (light, ultrasound, and temperature change), allows great flexibility in the design of stimuli-responsive dendrimers. In this review article, we will highlight recent advances and opportunities in the development of stimuli-responsive dendrimers for the treatment of various diseases, with emphasis on cancer. Specifically, the applications of stimuli-responsive dendrimers in drug delivery as well as their mechanisms are intensively reviewed.

  7. Dendrimers for siRNA Delivery

    Directory of Open Access Journals (Sweden)

    Swati Biswas

    2013-02-01

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

  8. Titanocene Dichloride Complexes Bonded to Carbosilane Dendrimers Via a Spacer of Variable Length – Molecular Dynamics Calculations and Catalysis of Allylic Coupling Reactions

    Czech Academy of Sciences Publication Activity Database

    Strašák, Tomáš; Jaroschik, F.; Malý, M.; Čermák, Jan; Sýkora, Jan; Fajgar, Radek; Karban, Jindřich; Harakat, D.

    2014-01-01

    Roč. 409, SI (2014), s. 137-146 ISSN 0020-1693 R&D Projects: GA MŠk(CZ) LC06070 Grant - others:UJEP(CZ) GA13-06989S Institutional support: RVO:67985858 Keywords : metallodendrimers * titanocene dichloride * allylic homocoupling * molecular dynamics Subject RIV: CC - Organic Chemistry Impact factor: 2.046, year: 2014

  9. Poly Ethoxy Ethyl Glycinamide (PEE-G) Dendrimers: Dendrimers Specifically Designed for Pharmaceutical Applications.

    Science.gov (United States)

    Toms, Steven; Carnachan, Susan M; Hermans, Ian F; Johnson, Keryn D; Khan, Ashna A; O'Hagan, Suzanne E; Tang, Ching-Wen; Rendle, Phillip M

    2016-08-05

    Poly ethoxy ethyl glycinamide (PEE-G) dendrimers have been specifically designed and synthesized with the aim of providing a readily available dendrimer scaffold that can be used to make products that can meet the stringent requirements of pharmaceutical applications. The synthesis has been refined to produce dendrimers that are of high HPLC purity. The suitability of PEE-G dendrimers for their designed use has been verified by subsequent measurements to demonstrate that they are of high stability, high aqueous solubility, low cytotoxicity, low immunogenicity and with low in vivo toxicity in an escalating-dose rat study. PEE-G dendrimers therefore provide a useful scaffold for researchers wanting to develop dendrimer-based drug candidates. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Dendrimer-based nanoparticles for cancer therapy.

    Science.gov (United States)

    Baker, James R

    2009-01-01

    Recent work has suggested that nanoparticles in the form of dendrimers may be a keystone in the future of therapeutics. The field of oncology could soon be revolutionized by novel strategies for diagnosis and therapy employing dendrimer-based nanotherapeutics. Several aspects of cancer therapy would be involved. Diagnosis using imaging techniques such as MRI will be improved by the incorporation of dendrimers as advanced contrast agents. This might involve novel contrast agents targeted specifically to cancer cells. Dendrimers can also be being applied to a variety of cancer therapies to improve their safety and efficacy. A strategy, somewhat akin to the "Trojan horse," involves targeting anti-metabolite drugs via vitamins or hormones that tumors need for growth. Further applications of dendrimers in photodynamic therapy, boron neutron capture therapy, and gene therapy for cancer are being examined. This presentation will cover the fundamentals of research utilizing dendrimers for cancer diagnosis and therapy. An evaluation of this new technologies will detail what advantage dendrimer based therapeutics might have over conventional cancer drugs.

  11. Cationic PAMAM dendrimers disrupt key platelet functions

    Science.gov (United States)

    Jones, Clinton F.; Campbell, Robert A.; Franks, Zechariah; Gibson, Christopher C.; Thiagarajan, Giridhar; Vieira-de-Abreu, Adriana; Sukavaneshvar, Sivaprasad; Mohammad, S. Fazal; Li, Dean Y.; Ghandehari, Hamidreza; Weyrich, Andrew S.; Brooks, Benjamin D.; Grainger, David W.

    2012-01-01

    Poly(amidoamine) (PAMAM) dendrimers have been proposed for a variety of biomedical applications and are increasingly studied as model nanomaterials for such use. The dendritic structure features both modular synthetic control of molecular size and shape and presentation of multiple equivalent terminal groups. These properties make PAMAM dendrimers highly functionalizable, versatile single-molecule nanoparticles with a high degree of consistency and low polydispersity. Recent nanotoxicological studies showed that intravenous administration of amine-terminated PAMAM dendrimers to mice was lethal, causing a disseminated intravascular coagulation-like condition. To elucidate the mechanisms underlying this coagulopathy, in vitro assessments of platelet functions in contact with PAMAM dendrimers were undertaken. This study demonstrates that cationic G7 PAMAM dendrimers activate platelets and dramatically alter their morphology. These changes to platelet morphology and activation state substantially altered platelet function, including increased aggregation and adherence to surfaces. Surprisingly, dendrimer exposure also attenuated platelet-dependent thrombin generation, indicating that not all platelet functions remained intact. These findings provide additional insight into PAMAM dendrimer effects on blood components and underscore the necessity for further research on the effects and mechanisms of PAMAM-specific and general nanoparticle toxicity in blood. PMID:22497592

  12. Controllable self-assembly of RNA dendrimers.

    Science.gov (United States)

    Sharma, Ashwani; Haque, Farzin; Pi, Fengmei; Shlyakhtenko, Lyudmila S; Evers, B Mark; Guo, Peixuan

    2016-04-01

    We report programmable self-assembly of branched, 3D globular, monodisperse and nanoscale sized dendrimers using RNA as building blocks. The central core and repeating units of the RNA dendrimer are derivatives of the ultrastable three-way junction (3WJ) motif from the bacteriophage phi29 motor pRNA. RNA dendrimers were constructed by step-wise self-assembly of modular 3WJ building blocks initiating with a single 3WJ core (Generation-0) with overhanging sticky end and proceeding in a radial manner in layers up to Generation-4. The final constructs were generated under control without any structural defects in high yield and purity, as demonstrated by gel electrophoresis and AFM imaging. Upon incorporation of folate on the peripheral branches of the RNA dendrimers, the resulting constructs showed high binding and internalization into cancer cells. RNA dendrimers are envisioned to have a major impact in targeting, disease therapy, molecular diagnostics and bioelectronics in the near future. Dendrimers are gaining importance as a carrier platform for diagnosis and therapeutics. The authors here reported building of their dendrimer molecules using RNA as building blocks. The addition of folate also allowed recognition and subsequent binding to tumor cells. This new construct may prove to be useful in many clinical settings. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Dendrimers in anticancer drug delivery: mechanism of interaction of drug and dendrimers.

    Science.gov (United States)

    Singh, Jaspreet; Jain, Keerti; Mehra, Neelesh Kumar; Jain, N K

    2016-11-01

    Dendrimers represents a novel class of macromolecules, which are derived from branches upon branches type structural design. Dendrimers are emerging as promising drug-delivery molecule because of their extraordinary properties including membrane interaction, monodispersity, well-defined size, shape and molecular weight, etc. Drugs interact with dendrimers in three ways; (a) physical encapsulation, (b) electrostatic interactions, and (c) covalent conjugations. Due to compact, globular structure and availability of interior cavity spaces and multiple surface functional groups, drug molecules can be encapsulated both in the interior of the dendrimers (physical encapsulation) as well as attached to the surface functional groups (covalent conjugations).

  14. Dendrimers as high relaxivity MR contrast agents.

    Science.gov (United States)

    Longmire, Michelle R; Ogawa, Mikako; Choyke, Peter L; Kobayashi, Hisataka

    2014-01-01

    Dendrimers are versatile macromolecules with tremendous potential as magnetic resonance imaging (MRI) contrast agents. Dendrimer-based agents provide distinct advantages over low-molecular-weight gadolinium chelates, including enhanced r1 relaxivity due to slow rotational dynamics, tunable pharmacokinetics that can be adapted for blood pool, liver, kidney, and lymphatic imaging, the ability to be a drug carrier, and flexibility for labeling due to their inherent multivalency. Clinical applications are increasingly being developed, particularly in lymphatic imaging. Herein we present a broad overview of dendrimer-based MRI contrast agents with attention to the unique chemistry and physical properties as well as emerging clinical applications. © 2013 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2016-06-01

    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.

  17. 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.

  18. On Topological Indices of Certain Dendrimer Structures

    Science.gov (United States)

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

    2017-05-01

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

  19. The Olefin Metathesis Reactions in Dendrimers

    Science.gov (United States)

    Astruc, Didier

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

  20. Dendrimers bind antioxidant polyphenols and cisplatin drug

    National Research Council Canada - National Science Library

    Abderrezak, Amine; Bourassa, Philippe; Mandeville, Jean-Sebastian; Sedaghat-Herati, Reza; Tajmir-Riahi, Heidar-Ali

    2012-01-01

    .... We examine the interaction of several dendrimers of different compositions mPEG-PAMAM (G3), mPEG-PAMAM (G4) and PAMAM (G4) with hydrophilic and hydrophobic drugs cisplatin, resveratrol, genistein and curcumin at physiological conditions...

  1. From dendrimers to fractal polymers and beyond

    OpenAIRE

    Moorefield, Charles N.; Schultz, Anthony; Newkome, George R.

    2013-01-01

    The advent of dendritic chemistry has facilitated materials research by allowing precise control of functional component placement in macromolecular architecture. The iterative synthetic protocols used for dendrimer construction were developed based on the desire to craft highly branched, high molecular weight, molecules with exact mass and tailored functionality. Arborols, inspired by trees and precursors of the utilitarian macromolecules known as dendrimers today, were the first examples to...

  2. Type III-B rotaxane dendrimers.

    Science.gov (United States)

    Ho, Watson K-W; Lee, Siu-Fung; Wong, Chi-Hin; Zhu, Xiao-Ming; Kwan, Chak-Shing; Chak, Chun-Pong; Mendes, Paula M; Cheng, Christopher H K; Leung, Ken Cham-Fai

    2013-11-28

    Type III-B first generation [3]rotaxane and second generation [4]rotaxane dendrimers have been synthesized via (1) a modified copper-catalyzed alkyne-azide cycloaddition (CuAAC), (2) Glaser-Hay's acetylenic oxidative homo-coupling, and (3) amide formation. The dendron does not reveal obvious cytotoxicities in L929 fibroblast cells. The rotaxane dendrimers can capture ammonia and are switchable both in solution and on surfaces.

  3. 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.

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

    DEFF Research Database (Denmark)

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

    2002-01-01

    the NH- and CO-stretch signals of the peptide amide moieties shift towards lower wave-numbers upon complexation with the dendrimer. Spatial analysis of the complexes with NOESY spectroscopy generally shows close proximity of the N-terminal Boc group of the peptide to the peripheral adamantyl groups......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...

  5. Construction of a well-defined multifunctional dendrimer for theranostics.

    Science.gov (United States)

    Ornelas, Cátia; Pennell, Ryan; Liebes, Leonard F; Weck, Marcus

    2011-03-04

    A dendrimer-based building block for theranostics was designed. The multifunctional dendrimer is polyamide-based and contains nine azide termini, nine amine termini, and fifty-four terminal acid groups. Orthogonal functionalization of the multifunctional dendrimer with a near-infrared (NIR) cyanine dye afforded the final dendrimer that shows fluorescence in the NIR region and no toxicity toward T98G human cells. The synthetic strategy described here might be promising for fabricating the next generation of materials for theranostics.

  6. Nanoparticulate platinum films on gold using dendrimer-based wet ...

    Indian Academy of Sciences (India)

    The stability of the films obtained with adsorbed dendrimers is emonstrated using the electrocatalytic reactions of fuels like methanol. The films formed without dendrimers cannot sustain the electro-oxidation currents due to the instability of the films while the films formed with dendrimers can sustain currents for longer ...

  7. Oligothia dendrimers for the formation of gold nanoparticles

    NARCIS (Netherlands)

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

    2004-01-01

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

  8. Dendrimers bind antioxidant polyphenols and cisplatin drug.

    Directory of Open Access Journals (Sweden)

    Amine Abderrezak

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

  9. Bifunctional Phosphorus Dendrimers and Their Properties.

    Science.gov (United States)

    Caminade, Anne-Marie; Majoral, Jean-Pierre

    2016-04-23

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

  10. PREPARATION OF CHEMICALLY WELL-DEFINED CARBOHYDRATE DENDRIMER CONJUGATES

    DEFF Research Database (Denmark)

    2004-01-01

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

  11. 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.

  12. 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.

  13. Targeted nanosystems: Advances in targeted dendrimers for cancer therapy.

    Science.gov (United States)

    Yang, Hu

    2016-02-01

    Dendrimers possess discrete highly compact nanostructures constituted of successive branched layers. Soon after the inception of dendrimers, recognition of their tunable structures and biologically favorable properties provoked a great enthusiasm in delving deeply into the utility of dendrimers for biomedical and pharmaceutical applications. One of the most important nanotechnology applications is the development of nanomedicines for targeted cancer therapies. Tremendous success in targeted therapies has been achieved with the use of dendrimer-based nanomedicines. This article provides a concise review on latest advances in the utility of dendrimers in immunotherapies and hormone therapies. Much basic and clinical research has been done since the invention of dendrimers, which are highly branched nano-sized molecules with the ability to act as carriers in nanomedicine. In this concise review article, the authors highlighted the current use of dendrimers in immunotherapies and hormone therapies in the fight against cancers. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Nitric Oxide-Releasing Dendrimers as Antibacterial Agents

    Science.gov (United States)

    Sun, Bin; Slomberg, Danielle L.; Chudasama, Shalini L.; Lu, Yuan

    2012-01-01

    The antibacterial activity of a series of nitric oxide (NO)-releasing poly(propylene imine) (PPI) dendrimers was evaluated against both Gram-positive and Gram-negative pathogenic bacteria, including methicillin-resistant Staphylococcus aureus. A direct comparison of the bactericidal efficacy between NO-releasing and control PPI dendrimers (i.e., non-NO-releasing) revealed both enhanced biocidal action of NO-releasing dendrimers and reduced toxicity against mammalian fibroblast cells. Antibacterial activity for the NO donor-functionalized PPI dendrimers was shown to be a function of both dendrimer size (molecular weight) and exterior functionality. In addition to minimal toxicity against fibroblasts, NO-releasing PPI dendrimers modified with styrene oxide exhibited the greatest biocidal activity (≥9.999% killing) against all bacterial strains tested. The N-diazeniumdiolate NO donor-functionalized PPI dendrimers presented in this study hold promise as effective NO-based therapeutics for combating bacterial infections. PMID:23013537

  15. Uses of Dendrimers for DNA Microarrays

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Majoral

    2006-08-01

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

  16. Dendrimer based nanotherapeutics for ocular drug delivery

    Science.gov (United States)

    Kambhampati, Siva Pramodh

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

  17. Dendrimers for Vaccine and Immunostimulatory Uses

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    Katsuhiko Sato

    2013-07-01

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

  20. Dendrimers as nanocarriers for nucleoside analogues.

    Science.gov (United States)

    Gorzkiewicz, Michał; Klajnert-Maculewicz, Barbara

    2017-05-01

    Dendrimers constitute a class of hyperbranched macromolecules with several potential applications due to their unique properties such as a well-defined structure, multivalency and biocompatibility. These polymers became one of the most promising drug nanocarriers, providing improved solubility of therapeutics, high loading capacity and controllable biodistribution pattern. In addition, the use of dendrimers as drug delivery devices in cancer therapies may help to overcome the resistance mechanisms by transporting activated drug molecules directly to cancer cells. In the recent years, dendrimers were intensively studied for delivery of nucleoside analogues (NAs), essential elements of antiviral therapies, as well as treatments of leukemia, lymphoma and various types of solid tumors. These agents act as antimetabolites, competing with physiological nucleosides, and interacting with intracellular enzymes and nuclear acids to induce cytotoxicity. However, efficiency of NAs-based therapies is often limited by factors like fast metabolism, disadvantageous biodistribution, low solubility and various side effects. In case of treatment of leukemia, target cells usually develop drug resistance, which reduces the activity of nucleoside analogues even further. Thus, drug carrier systems are studied to improve the efficacy and specificity of action of these compounds. In this review, we summarize available data concerning the possibility of application of dendrimers as delivery devices for nucleoside analogues and their active, triphosphate forms. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. 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.

  2. Au nanoparticles stabilised by PEGylated low generation PAMAM dendrimers: design, characterisation and properties.

    Science.gov (United States)

    Dietrich, Sascha; Schulze, Steffen; Hietschold, Michael; Lang, Heinrich

    2011-07-15

    The preparation and characterisation of a series of well-defined low generation (poly)amidoamine (PAMAM)-based dendrimers with end-grafted ethylene glycol ether moieties of type N(CH(2)CH(2)C(O)NHCH(2)CH(2)NR(2))(3) (3a, R=CH(2)CH(2)C(O)OCH(2)CH(2)OCH(3); 3b, R=CH(2)CH(2)C(O)O(CH(2)CH(2)O)(2)C(2)H(5); 3c, R=CH(2)CH(2)C(O)O(CH(2)CH(2)O)(9)CH(3)), [CH(2)N(CH(2)CH(2)C(O)NHCH(2)CH(2)NR(2))(2)](2) (4, R=CH(2)CH(2)C(O)O(CH(2)CH(2)O)(2)C(2)H(5)) and (R(2)NCH(2)CH(2)NHC(O)CH(2)CH(2))N[CH(2)CH(2)N(CH(2)CH(2)C(O)NHCH(2)CH(2)NR(2))(2)](2) (5a, R=CH(2)CH(2)C(O)OCH(2)CH(2)OCH(3); 5b, R=CH(2)CH(2)C(O)O(CH(2)CH(2)O)(2)C(2)H(5); 5c, R=CH(2)CH(2)C(O)O(CH(2)CH(2)O)(9)CH(3)) and their application for the stabilisation of gold nanoparticles (Au NPs) is described. These dendrimers were prepared by a consecutive divergent synthesis methodology including Michael addition and amidation cycles. For comparison, amidoamine related model compounds N(C(3)H(7))R(2) (1, R=CH(2)CH(2)C(O)O(CH(2)CH(2)O)(2)C(2)H(5)) and [CH(2)NR(2)](2) (2, R=CH(2)CH(2)C(O)O(CH(2)CH(2)O)(2)C(2)H(5)) were also synthesised to estimate the minimum required donating capabilities of the stabiliser. Loading the appropriate dendritic templates with H[AuCl(4)] (12) and subsequent reduction of the respective metallodendrimers with Na[BH(4)] produced dendrimer encapsulated gold colloids. The dendrimeric scaffold, the length of the ethylene glycols, the adjusted stabilizer:gold ratio and the duration of reaction time affects the average Au particle diameter in a range of 4.0 (±0.9) to 58.5 (±14.5) nm. Furthermore, depending on the nature of the stabiliser, nanoparticles were formed having spherical or multiple morphologies. Characterisation by transmission electron microscopy (TEM), dynamic light scattering (DLS), UV/vis, and IR spectroscopy revealed that Au NPs are formed and protected inside the dendrimer scaffold. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Influence of PAMAM dendrimers on the human insulin

    Science.gov (United States)

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

    2015-12-01

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

  4. MOLECULAR DYNAMICS SIMULATION OF LYSINE DENDRIMER AND SEMAX PEPTIDES INTERACTION

    Directory of Open Access Journals (Sweden)

    E. V. Popova

    2016-07-01

    Full Text Available The paper deals with the possibility of complex formation of therapeutic Semax peptides with lysine dendrimer by molecular modeling methods. Dendrimers are often used for delivery of drugs and biological molecules (e.g., DNA, peptides and polysaccharides. Since lysine dendrimers are less toxic than conventional synthetic dendrimers (e.g., polyamidoamine (PAMAM dendrimer, we chose them and studied two systems containing dendrimer and the different number of Semax peptides. The study was carried out by molecular dynamics method. It was obtained that the stable complexes were formed in both cases. The equilibrium structures of these complexes were investigated. These complexes can be used in the future in therapy of various diseases as Semax peptides have significant antioxidant, antihypoxic and neuroprotecting action.

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

    Science.gov (United States)

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

    2011-11-01

    Dendrimers are highly branched macromolecules with the potential to be used for biomedical applications. Several dendrimers are toxic owing to their positively charged surfaces. However, this toxicity can be reduced by coating these peripheral cationic groups with carbohydrate residues. In this study, the toxicity of three types of 4th generation poly (propyleneimine) dendrimers were investigated in vivo; uncoated (PPI-g4) dendrimers, and dendrimers in which 25% or 100% of surface amino groups were coated with maltotriose (PPI-g4-25%m or PPI-g4-100%m), were administered to Wistar rats. Body weight, food and water consumption, and urine excretion were monitored daily. Blood was collected to investigate biochemical and hematological parameters, and the general condition and behavior of the animals were analyzed. Unmodified PPI dendrimers caused changes in the behavior of rats, a decrease in food and water consumption, and lower body weight gain. In the case of PPI-g4 and PPI-g4-25%m dendrimers, disturbances in urine and hematological and biochemical profiles returned to normal during the recovery period. PPI-g4-100%m was harmless to rats. The PPI dendrimers demonstrated dose- and sugar-modification-degree dependent toxicity. A higher dose of uncoated PPI dendrimers caused toxicity, but surface modification almost completely abolished this toxic effect. Copyright © 2011 Wiley Periodicals, Inc.

  6. Peptide-Decorated Dendrimers and Their Bioapplications.

    Science.gov (United States)

    Wan, Jingjing; Alewood, Paul F

    2016-04-18

    Peptide-decorated dendrimers (PDDs) are a class of spherical, regular, branched polymers that are modified by peptides covalently attached to their surface. PDDs have been used as protein mimetics, novel biomaterials, and in a wide range of biomedical applications. Since their design and development in the late eighties, poly-l-lysine has been a preferred core structure for PDDs. However, numerous recent innovations in polymer synthesis and ligation chemistry have re-energized the field and led to the emergence of well-defined peptide dendrimers with more diverse core structures and functions. This Minireview highlights the development of PDDs driven by significantly improved ligation chemistry incorporating structurally well-defined peptides and the emerging use of PDDs in imaging and drug development. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Dendrimer effects on peptide and protein fibrillation

    DEFF Research Database (Denmark)

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

    2007-01-01

    Dendrimers are synthetic, symmetrically branched polymers that can be manufactured to a high degree of definition and therefore present themselves as monodisperse entities. Flexible and globular in shape and compartementalized into a partly inaccessible interior and a highly exposed surface......, they offer numerous possibilities for interactions with and responses to biological macromolecules and biostructures including cell membranes and proteins. By way of their multiple functional surface groups, they allow the design of surfaces carrying a multitude of biological motifs and/or charges giving...... rise to quite significant biological and physico-chemical effects. Here we describe the surprising ability of dendrimers to interact with and perturb polypeptide conformations, particularly efficiently towards amyloid structures; that is, the structures of highly insoluble polypeptide aggregates...

  8. 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.

  9. Interplay of Oxidative Stress and Autophagy in PAMAM Dendrimers-Induced Neuronal Cell Death.

    Science.gov (United States)

    Li, Yubin; Zhu, Haiyan; Wang, Shaofei; Qian, Xiaolu; Fan, Jiajun; Wang, Ziyu; Song, Ping; Zhang, Xuesai; Lu, Weiyue; Ju, Dianwen

    2015-01-01

    Poly-amidoamine (PAMAM) dendrimers are proposed to be one of the most promising drug-delivery nanomaterials. However, the toxicity of PAMAM dendrimers on the central nervous system seriously hinders their medical applications. The relationship between oxidative stress and autophagy induced by PAMAM dendrimers, and its underlying mechanism remain confusing. In this study, we reported that PAMAM dendrimers induced both reactive oxygen species and autophagy flux in neuronal cells. Interestingly, autophagy might be triggered by the formation of reactive oxygen species induced by PAMAM dendrimers. Suppression of reactive oxygen species could not only impair PAMAM dendrimers-induced autophagic effects, but also reduce PAMAM dendrimers-induced neuronal cell death. Moreover, inhibition of autophagy could protect against PAMAM dendrimers-induced neuronal cell death. These findings systematically elucidated the interplay between oxidative stress and autophagy in the neurotoxicity of PAMAM dendrimers, which might encourage the application of antioxidants and autophagy inhibitors to ameliorate the neurotoxicity of PAMAM dendrimers in clinic.

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

    African Journals Online (AJOL)

    Purpose: To develop peptide-dendrimer-paclitaxel conjugates for the treatment of heterogeneous stage. 1 non small cell lung cancer (NSCLC) in 293T and L132cell line. Method: Dendrimer-paclitaxel conjugates (PAMAM-PTX) were prepared by NHS method and the conjugates were used for the synthesis of ...

  11. Elasticity of single poly(amido amine) dendrimers

    NARCIS (Netherlands)

    Tomczak, N.; Vancso, Gyula J.

    2007-01-01

    An atomic force microscope in the compression mode was used to probe the nanomechanical response of single dendrimeric molecules, as well as dendrimer aggregates adsorbed on silicon surface. The force-compression behaviour of individual, generation 5 poly(amido amine) (PAMAM) dendrimers was

  12. Inhibition of autophagy protects against PAMAM dendrimers-induced hepatotoxicity.

    Science.gov (United States)

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

    2015-05-01

    Toxicity of nanomaterials is one of the biggest challenges in their medicinal applications. Although toxicities of nanomaterials have been widely reported, the exact mechanisms of toxicities are still not well elucidated. Consequently, the exploration of approaches to attenuate toxicities of nanomaterials is limited. In this study, we reported that poly-amidoamine (PAMAM) dendrimers, a widely used nanomaterial in the pharmaceutical industry, caused toxicity of human liver cells by inducing cell growth inhibition, mitochondria damage, and apoptosis. Meanwhile, autophagy was activated in PAMAM dendrimers-induced toxicity and inhibition of autophagy-rescued viability of hepatic cells, indicating that autophagy played a key role in PAMAM dendriemrs-induced hepatotoxicity. To further explore approaches to attenuate PAMAM dendrimers-induced liver injury, effects of autophagic inhibitors on PAMAM dendrimers' hepatotoxicity were investigated in an in vivo model. Autophagy blockage in PAMAM dendrimers-administered mice led to weight restoration, damage reversion of liver tissue, and protection against changes of serum biochemistry parameters. Moreover, inhibition of Akt/mTOR and activation of Erk1/2 signaling pathways were involved in PAMAM dendrimers-induced autophagy. Collectively, these findings indicated that autophagy was associated with PAMAM dendrimers-induced hepatotoxicity, and supported the possibility that autophagy inhibitors could be used to reduce hepatotoxicity of PAMAM dendrimers.

  13. Bioapplications of poly(amidoamine) (PAMAM) dendrimers in nanomedicine

    Science.gov (United States)

    Taghavi Pourianazar, Negar; Mutlu, Pelin; Gunduz, Ufuk

    2014-04-01

    Poly(amidoamine) (PAMAM) dendrimers are a novel class of spherical, well-designed branching polymers with interior cavities and abundant terminal groups on the surface which can form stable complexes with drugs, plasmid DNA, oligonucleotides, and antibodies. Amine-terminated PAMAM dendrimers are able to solubilize different families of hydrophobic drugs, but the cationic charges on dendrimer surface may disturb the cell membrane. Therefore, surface modification by PEGylation, acetylation, glycosylation, and amino acid functionalization is a convenient strategy to neutralize the peripheral amine groups and improve dendrimer biocompatibility. Anticancer agents can be either encapsulated in or conjugated to dendrimer and be delivered to the tumor via enhanced permeability and retention (EPR) effect of the nanoparticle and/or with the help of a targeting moiety such as antibody, peptides, vitamins, and hormones. Biodegradability, non-toxicity, non-immunogenicity, and multifunctionality of PAMAM dendrimer are the key factors which facilitate steady increase of its application in drug delivery, gene transfection, tumor therapy, and diagnostics applications with precision and selectivity. This review deals with the major topics of PAMAM dendrimers including structure, synthesis, toxicity, surface modification, and also possible new applications of these spherical polymers in biomedical fields as dendrimer-based nanomedicine.

  14. Wiring of heme enzymes by methylene-blue labeled dendrimers

    DEFF Research Database (Denmark)

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

    2017-01-01

    - 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...

  15. Dendrimers in Medicine: Therapeutic Concepts and Pharmaceutical Challenges.

    Science.gov (United States)

    Wu, Lin-Ping; Ficker, Mario; Christensen, Jørn B; Trohopoulos, Panagiotis N; Moghimi, Seyed Moein

    2015-07-15

    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 characteristics, as well as multivalency. Collectively, these physicochemical characteristics together with advancements in design of biodegradable backbones have conferred many applications to dendrimers in formulation science and nanopharmaceutical developments. These have included the use of dendrimers as pro-drugs and vehicles for solubilization, encapsulation, complexation, delivery, and site-specific targeting of small-molecule drugs, biopharmaceuticals, and contrast agents. We briefly review these advances, paying particular attention to attributes that make dendrimers versatile for drug formulation as well as challenging issues surrounding the future development of dendrimer-based medicines.

  16. Dendrimers as Potential Therapeutic Tools in HIV Inhibition

    Directory of Open Access Journals (Sweden)

    Xiangbo Li

    2013-07-01

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

  17. Anti-Inflammatory Properties of Dendrimers per se

    Directory of Open Access Journals (Sweden)

    Myriam Hayder

    2011-01-01

    Full Text Available Dendrimers are polybranched and polyfunctionalized tree-like polymers. Unlike linear polymers, they have perfectly defined structure and molecular weight, due to their iterative step-by-step synthesis. Their multivalent structure and supramolecular properties have made them attractive nanotools for applications, particularly in biology and medicine. Among the different biological and medical properties of dendrimers that have been developed over the past decades, the anti-inflammatory properties of several groups of dendrimers are the most recently discovered. Thereof, dendrimers emerge as promising, although heretical, drug candidates for the treatment of still-uncured chronic inflammatory disorders. This mini-review is based on the five main scientific articles giving an overview of what can be the spectrum of anti-inflammatory characteristics displayed by dendrimers.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-03-15

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

  19. Counterion Condensation and Effective Charge of PAMAM Dendrimers

    Directory of Open Access Journals (Sweden)

    Ulrich Scheler

    2011-04-01

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

  20. 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.

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

    Science.gov (United States)

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

    2017-12-01

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

  2. The specific functionalization of cyclotriphosphazene for the synthesis of smart dendrimers.

    Science.gov (United States)

    Caminade, Anne-Marie; Hameau, Aurélien; Majoral, Jean-Pierre

    2016-02-07

    Hexachlorocyclotriphosphazene is an old compound which affords very new properties in the field of dendrimers. Indeed, it can be used as a branching point for the rapid synthesis of highly dense dendrimers, but also for the synthesis of dendrimers having precisely one function different from all the others. These types of dendrimers are useful in the field of materials, affording highly reusable catalysts, chemical sensors, or supports for cell cultures. However, the most developed uses concern fluorescence. These dendrimers have been used for in vivo imaging, and for trying to elucidate biological mechanisms, in particular for anti-inflammatory dendrimers. This review will display important examples in the field.

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

    Science.gov (United States)

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

    2011-12-01

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

  4. From dendrimers to fractal polymers and beyond

    Directory of Open Access Journals (Sweden)

    Charles N. Moorefield

    2013-01-01

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

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

    Science.gov (United States)

    2013-01-01

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

  6. Disruption of Amyloid Prion Protein Aggregates by Cationic Pyridylphenylene Dendrimers.

    Science.gov (United States)

    Sorokina, Svetlana A; Stroylova, Yulia Yu; Shifrina, Zinaida B; Muronetz, Vladimir I

    2016-02-01

    Disruption of amyloid protein aggregates is one of the potential therapies for treatment of neurodegenerative disorders such as prion diseases. Here, for the first time we report that pH-independent cationic pyridylphenylene dendrimers are able to disrupt amyloid protein aggregates at physiological pH as exemplified by inclusion bodies of ovine prion protein. The results show that exposure of inclusion bodies to the dendrimers leads to its partial disaggregation and release of the nanosize protein-dendrimer complexes. The complexes were characterized by SDS PAGE, DLS, and Western blotting methods. Thioflavin T fluorescence clearly demonstrated a decrease of amyloidogenic capability of the prion protein upon exposure to the dendrimers. The complexes formed are stable and do not show further aggregation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Advances in Photofunctional Dendrimers for Solar Energy Conversion.

    Science.gov (United States)

    Zhang, Xiaohui; Zeng, Yi; Yu, Tianjun; Chen, Jinping; Yang, Guoqiang; Li, Yi

    2014-07-03

    Dendrimers are regularly and hierarchically branched synthetic macromolecules with numerous chain ends all emanating from a single core, which makes them attractive candidates for energy conversion applications. During photosynthesis and photocatalysis, photoinduced electron transfer and energy transfer are the main processes involved. Studies on these processes in dendritic systems are critical for the future applications of dendrimers in photochemical energy conversion and other optoelectronic devices. In this Perspective, the recent advances of photofunctional dendrimers in energy conversion based on light-harvesting systems, solar cells, and photochemical production of hydrogen will be discussed. The electron-transfer and energy-transfer characteristics in light-harvesting photofunctional dendrimers and the regulation of the electron-transfer process and the stabilization of the charge separation state in hydrogen photoproduction are emphasized.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-01-01

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

  9. Dendrimer-entrapped metal colloids as imaging agents.

    Science.gov (United States)

    Li, Du; Wen, Shihui; Shi, Xiangyang

    2015-01-01

    This review reports the recent advances in dendrimer-entrapped metal colloids as contrast agents for biomedical imaging applications. The versatile dendrimer scaffolds with 3-dimensional spherical shape, highly branched internal cavity, tunable surface conjugation chemistry, and excellent biocompatibility and nonimmunogenicity afford their uses as templates to create multifunctional dendrimer-entrapped metal colloids for mono- or multi- mode molecular imaging applications. In particular, multifunctional dendrimer-entrapped gold nanoparticles with different surface modifications have been used for fluorescence imaging, targeted tumor computed tomography (CT) imaging, enhanced blood pool CT imaging, dual mode CT/MR imaging, and tumor theranostics (combined CT imaging and chemotherapy) will be introduced and discussed in detail. © 2015 Wiley Periodicals, Inc.

  10. An emerging class of amphiphilic dendrimers for pharmaceutical and biomedical applications: Janus amphiphilic dendrimers.

    Science.gov (United States)

    Sikwal, Dhiraj R; Kalhapure, Rahul S; Govender, Thirumala

    2017-01-15

    In recent years, a new class of dendrimer, known as Janus dendrimers (JDs), has attracted much attention due to their different structures and properties to the conventional symmetric forms. The broken symmetry of JDs offers the opportunity to form complex self-assembled materials, and presents new sets of properties that are presently inconceivable for homogeneous or symmetrical dendrimers. Due to their unique features, JDs have a promising future in pharmaceutical and biomedical fields, as seen from the recent interest in their application in conjugating multiple drugs and targeting moieties, forming supramolecular hydrogels, enabling micellar delivery systems, and preparing nano-vesicles, known as dendrimersomes, for drug encapsulation. The present paper is the first review, with an emphasis on various emerging applications of JDs, in the drug delivery and biomedical field reported so far. In addition, the paper describes different synthetic methods for producing JDs that can guide the design of new biocompatible forms with pharmacological activities, and that have the potential to be nano drug delivery vehicles. Furthermore, future studies to optimize the applications of JDs in drug delivery sciences and biomedical field to realize their potential to treat various disease conditions are identified and highlighted. Overall, this review identifies the current status of JDs in terms of their synthesis and applications, as well as the future research for their translation into macromolecules for clinical applications to solve health problems. It highlights the future combined efforts needed to be taken by dendrimer chemists, formulation scientist and microbiologists to develop novel antibacterials and nanomedicines from JDs. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Kanika Madaan

    2014-01-01

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

  12. Dendrimer-based contrast agents for molecular imaging.

    Science.gov (United States)

    Longmire, Michelle; Choyke, Peter L; Kobayashi, Hisataka

    2008-01-01

    The extensive adaptability of dendrimer-based contrast agents is ideal for the molecular imaging of organs and other target-specific locations. The ability of literally atom-by-atom modification on cores, interiors, and surface groups, permits the rational manipulation of dendrimer-based agents in order to optimize their physical characteristics, biodistribution, receptor-mediated targeting, and controlled release of the payload. Such modifications enable agents to localize preferentially to areas or organs of interest for facilitating target-specific imaging as well as assume excretion pathways that do not interfere with desired applications. Recent innovations in dendrimer research have increased agent directibility and new synthetic chemistry approaches have increased efficiency of production as well as led to the creation of novel dendrimer-based contrast agents. In addition, by taking advantage of the numerous attachment sites available on the surface of a single dendrimer molecule, new synthetic chemistry techniques have led to the development of multi-modality magnetic resonance, radionuclide, and fluorescence imaging agents for molecular imaging. Herein we discuss advances in dendrimer-based contrast agents for molecular imaging focusing mainly on the chemical design as applied to optical, magnetic resonance, computer tomography, radionuclide, and multi-modality imaging.

  13. 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.

  14. Polyphenylene dendrimers as scaffolds for shape-persistent multiple peptide conjugates

    NARCIS (Netherlands)

    Mihov, Gueorgui; Grebel-Koehler, Dörthe; Lübbert, Anke; Vandermeulen, Guido W.M.; Herrmann, Andreas; Klok, Harm-Anton; Müllen, Klaus

    2005-01-01

    The present work describes synthetic concepts for the coupling of peptides to polyphenylene dendrimers (PPDs). Novel functionalized cyclopentadienones have been synthesized whose Diels-Alder cycloaddition with various core molecules leads to polyphenylene dendrimers possessing (protected) amino or

  15. 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

  16. 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.

  17. IMMUNOSTIMULATORY PROPERTIES OF DENDRIMERS MULTIVALENTLY PRESENTING MURAMYLDIPEPTIDE

    DEFF Research Database (Denmark)

    an upregulation of B7 and MHC class II after 24 hours of culture in medium. However, after culture with PGN or MDP-conjugated dendrimers, the monocytes had down-regulated both markers to a degree that corresponded with the magnitude of cytokine production. Conclusion: These results indicate that it is possible......) are evolutionarily conserved microbial structures, generally composed of repeated molecular units of small size, and recognized by pattern-recognition receptors (PRRs). Binding of PAMPs to certain PRRs induces dendritic cells to express costimulatory molecules and inflammatory cytokines, enabling an inductive...... a theoretical number of 16 and 32 MDP molecules, respectively. These conjugates were tested for cytotoxicity, and for their ability to induce cytokines and upregulate MHC and costimulatory molecules in porcine peripheral blood mononuclear cells. Results: Both MDP-PPI and MDP-PAMAM conjugates induced...

  18. Influence of peptide dendrimers and sonophoresis on the transdermal delivery of ketoprofen.

    Science.gov (United States)

    Manikkath, Jyothsna; Hegde, Aswathi R; Kalthur, Guruprasad; Parekh, Harendra S; Mutalik, Srinivas

    2017-04-15

    The aim of this study was to determine the individual and combined effects of peptide dendrimers and low frequency ultrasound on the transdermal permeation of ketoprofen. Arginine terminated peptide dendrimers of varying charges (4(+), 8(+) and 16(+), named as A4. A8 and A16 respectively) were synthesized and characterized. Ketoprofen was subjected to passive, peptide dendrimer-assisted and sonophoretic permeation studies (with and without dendrimer application) across Swiss albino mouse skin, both in vitro and in vivo. The studies revealed that the synthesized peptide dendrimers considerably increased the transdermal permeation of ketoprofen and displayed enhancement ratios of up to 3.25 (with A16 dendrimer), compared to passive diffusion of drug alone in vitro. Moreover, the combination of peptide dendrimer treatment and ultrasound application worked in synergy and gave enhancement ratios of up to 1369.15 (with ketoprofen-A16 dendrimer complex). In vivo studies demonstrated that dendrimer and ultrasound-assisted permeation of drug achieved much higher plasma concentration of drug, compared to passive diffusion. Comparison of transdermal and oral absorption studies revealed that transdermal administration of ketoprofen with A8 dendrimer showed comparable absorption and plasma drug levels with oral route. The excised mouse skin after in vivo permeation study with dendrimers and ultrasound did not show major toxic reactions. This study demonstrates that arginine terminated peptide dendrimers combined with sonophoresis can effectively improve the transdermal permeation of ketoprofen. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. 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…

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

    NARCIS (Netherlands)

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

    2002-01-01

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

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

    Science.gov (United States)

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

    2016-05-01

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

  2. Dendrimers Bind Antioxidant Polyphenols and cisPlatin Drug

    Science.gov (United States)

    Abderrezak, Amine; Bourassa, Philippe; Mandeville, Jean-Sebastian; Sedaghat-Herati, Reza; Tajmir-Riahi, Heidar-Ali

    2012-01-01

    Synthetic polymers of a specific shape and size play major role in drug delivery systems. Dendrimers are unique synthetic macromolecules of nanometer dimensions with a highly branched structure and globular shape with potential applications in gene and drug delivery. We examine the interaction of several dendrimers of different compositions mPEG-PAMAM (G3), mPEG-PAMAM (G4) and PAMAM (G4) with hydrophilic and hydrophobic drugs cisplatin, resveratrol, genistein and curcumin at physiological conditions. FTIR and UV-visible spectroscopic methods as well as molecular modeling were used to analyse drug binding mode, the binding constant and the effects of drug complexation on dendrimer stability and conformation. Structural analysis showed that cisplatin binds dendrimers in hydrophilic mode via Pt cation and polymer terminal NH2 groups, while curcumin, genistein and resveratrol are located mainly in the cavities binding through both hydrophobic and hydrophilic contacts. The overall binding constants of durg-dendrimers are ranging from 102 M−1 to 103 M−1. The affinity of dendrimer binding was PAMAM-G4>mPEG-PAMAM-G4>mPEG-PAMAM-G3, while the order of drug-polymer stability was curcumin>cisplatin>genistein>resveratrol. Molecular modeling showed larger stability for genisten-PAMAM-G4 (ΔG = −4.75 kcal/mol) than curcumin-PAMAM-G4 ((ΔG = −4.53 kcal/mol) and resveratrol-PAMAM-G4 ((ΔG = −4.39 kcal/mol). Dendrimers might act as carriers to transport hydrophobic and hydrophilic drugs. PMID:22427960

  3. Structure-activity relationships of fluorinated dendrimers in DNA and siRNA delivery.

    Science.gov (United States)

    Wang, Mingming; Cheng, Yiyun

    2016-12-01

    Fluorinated dendrimers have shown great promise in gene delivery due to their high transfection efficacy and low cytotoxicity, however, the structure-activity relationships of these polymers still remain unknown. Herein, we synthesized a library of fluorinated dendrimers with different dendrimer generations and fluorination degrees and investigated their behaviors in both DNA and siRNA delivery. The results show that fluorination significantly improves the transfection efficacy of G4-G7 polyamidoamine dendrimers in DNA and siRNA delivery. Fluorination on generation 5 dendrimer yields the most efficient polymers in gene delivery, and the transfection efficacy of fluorinated dendrimers depends on fluorination degree. All the fluorinated dendrimers cause minimal toxicity on the transfected cells at their optimal transfection conditions. This study provides a general and facile strategy to prepare high efficient and low cytotoxic gene carriers based on fluorinated polymers. The structure-activity relationships of fluorinated dendrimers in gene delivery is still unknown and the behavior of fluorinated dendrimers in siRNA delivery has not yet been investigated. Herein, we synthesized a library of fluorinated PAMAM dendrimers with different dendrimer generations and fluorination degrees and investigated their behaviors in both DNA and siRNA delivery. The results clearly indicate that fluorination significantly improves the transfection efficacy of dendrimers in both DNA and siRNA delivery without causing additional toxicity. G5 PAMAM dendrimer is best scaffold to synthesize fluorinated dendrimers and the transfection efficacy of fluorinated dendrimers depends on fluorination degree. This systematic study provides a general and facile strategy to prepare high efficient and low cytotoxic gene carriers based on fluorinated polymers. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    Pryor, Joseph B; Harper, Bryan J; Harper, Stacey L

    2014-01-01

    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 contributors to the toxicity of dendrimers. Further studies are required to better understand the relative role each plays in driving the toxicity of dendrimers. To the best of our knowledge, this is the first in vivo study to address such a broad range of dendrimers. PMID:24790436

  5. Mechanism of PAMAM Dendrimers Internalization in Hippocampal Neurons.

    Science.gov (United States)

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

    2016-10-03

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

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

    Directory of Open Access Journals (Sweden)

    Domenico Lombardo

    2014-01-01

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

  7. Cationic PAMAM Dendrimers as Pore-Blocking Binary Toxin Inhibitors

    Science.gov (United States)

    2015-01-01

    Dendrimers are unique highly branched macromolecules with numerous groundbreaking biomedical applications under development. Here we identified poly(amido amine) (PAMAM) dendrimers as novel blockers for the pore-forming B components of the binary anthrax toxin (PA63) and Clostridium botulinum C2 toxin (C2IIa). These pores are essential for delivery of the enzymatic A components of the internalized toxins from endosomes into the cytosol of target cells. We demonstrate that at low μM concentrations cationic PAMAM dendrimers block PA63 and C2IIa to inhibit channel-mediated transport of the A components, thereby protecting HeLa and Vero cells from intoxication. By channel reconstitution and high-resolution current recording, we show that the PAMAM dendrimers obstruct transmembrane PA63 and C2IIa pores in planar lipid bilayers at nM concentrations. These findings suggest a new potential role for the PAMAM dendrimers as effective polyvalent channel-blocking inhibitors, which can protect human target cells from intoxication with binary toxins from pathogenic bacteria. PMID:24954629

  8. Transepithelial transport of PAMAM dendrimers across isolated intestinal tissue

    Science.gov (United States)

    Hubbard, Dallin A.

    Poly(amido amine) (PAMAM) dendrimers have shown potential to carry poorly absorbed drugs across the intestinal barrier and into systemic circulation, reducing the need for intravenous injections. Much of the in vitro transepithelial transport of PAMAM dendrimers to date has been investigated using Caco-2 monolayers which lack the microvilli morphology and enzymes present in isolated intestinal tissues. In addition, a challenge in predicting oral absorption is establishing a correlation between transport across rodent and human intestinal tissues. This dissertation focused on investigating the transepithelial transport of PAMAM dendrimers across rat and human isolated intestinal tissues. Permeability values in isolated tissues were compared with those across Caco-2 cell monolayers. Results indicate a difference in transport of PAMAM dendrimers, morphological changes and transepithelial electrical resistance between Caco-2 cell monolayers, rat and human intestinal tissue models. A relatively high transport rate across the tissues, given the macromolecular nature of PAMAM dendrimers, shows promise for use of these constructs for oral delivery in human.

  9. 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.

  10. Dendrimers for vaccine and immunostimulatory uses. A review.

    Science.gov (United States)

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

    2010-03-17

    Dendrimers are well-defined (monodisperse) synthetic globular polymers with a range of interesting chemical and biological properties. Chemical properties include the presence of multiple accessible surface functional groups that can be used for coupling biologically relevant molecules and methods that allow for precise heterofunctionalization of surface groups. Biologically, dendrimers are highly biocompatible and have predictable biodistribution and cell membrane interacting characteristics determined by their size and surface charge. Dendrimers have optimal characteristics to fill the need for efficient immunostimulating compounds (adjuvants) that can increase the efficiency of vaccines, as dendrimers can provide molecularly defined multivalent scaffolds to produce highly defined conjugates with small molecule immunostimulators and/or antigens. The review gives an overview on the use of dendrimers as molecularly defined carriers/presenters of small antigens, including constructs that have built-in immunostimulatory (adjuvant) properties, and as stand-alone adjuvants that can be mixed with antigens to provide efficient vaccine formulations. These approaches allow the preparation of molecularly defined vaccines with highly predictable and specific properties and enable knowledge-based vaccine design substituting the traditional empirically based approaches for vaccine development and production.

  11. Toxicology of Engineered Nanoparticles: Focus on Poly(amidoamine) Dendrimers.

    Science.gov (United States)

    Naha, Pratap C; Mukherjee, Sourav P; Byrne, Hugh J

    2018-02-14

    Engineered nanomaterials are increasingly being developed for paints, sunscreens, cosmetics, industrial lubricants, tyres, semiconductor devices, and also for biomedical applications such as in diagnostics, therapeutics, and contrast agents. As a result, nanomaterials are being manufactured, transported, and used in larger and larger quantities, and potential impacts on environmental and human health have been raised. Poly(amidoamine) (PAMAM) dendrimers are specifically suitable for biomedical applications. They are well-defined nanoscale molecules which contain a 2-carbon ethylenediamine core and primary amine groups at the surface. The systematically variable structural architecture and the large internal free volume make these dendrimers an attractive option for drug delivery and other biomedical applications. Due to the wide range of applications, the Organisation for Economic Co-Operation and Development (OECD) have included them in their list of nanoparticles which require toxicological assessment. Thus, the toxicological impact of these PAMAM dendrimers on human health and the environment is a matter of concern. In this review, the potential toxicological impact of PAMAM dendrimers on human health and environment is assessed, highlighting work to date exploring the toxicological effects of PAMAM dendrimers.

  12. Potent Antioxidant Dendrimers Lacking Pro-oxidant Activity

    Science.gov (United States)

    Lee, Choon Young; Sharma, Ajit; Uzarski, Rebecca L.; Cheong, Jae Eun; Xu, Hao; Held, Rich A.; Upadhaya, Samik K.; Nelson, Julie L.

    2010-01-01

    It is well known that antioxidants have protective effects against oxidative stress. Unfortunately, in the presence of transition metals, antioxidants including polyphenols with potent antioxidant activities may also exhibit pro-oxidant effects, which may irreversibly damage DNA. Therefore, antioxidants with strong free radical scavenging abilities and devoid of pro-oxidant effects would be of immense biological importance. We report two antioxidant dendrimers with a surface rich in multiple phenolic hydroxyl groups, benzylic hydrogens and electron donating ring substituents that contribute to their potent free radical quenching property. In order to minimize their pro-oxidant effects, the dendrimers were designed with a metal chelating tris(2-aminoethyl)amine (TREN) core. The dendritic antioxidants were prepared by attachment of six syringaldehyde or vanillin molecules to TREN by reductive amination. They exhibited potent radical scavenging properties: 5 times stronger than quercetin and 15 times more potent than Trolox according to the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The antioxidant dendrimers also protected low-density lipoprotein, lysozyme and DNA against 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced free radical damage. More importantly, unlike quercetin and Trolox, the two TREN antioxidant dendrimers did not damage DNA via their pro-oxidant effects when incubated with physiological amounts of copper ions. The dendrimers also showed no cytotoxicity towards Chinese hamster ovary cells. PMID:20977937

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

    Directory of Open Access Journals (Sweden)

    Ali Akbar Zolriasatein

    2015-03-01

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

  14. The role of autophagy in the neurotoxicity of cationic PAMAM dendrimers.

    Science.gov (United States)

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

    2014-08-01

    Poly(amidoamine) (PAMAM) dendrimers, are among the most common classes of dendrimers that are intended for a wide range of biomedical applications and extensively investigated for brain-specific drug delivery, imaging and diagnosis. Unfortunately, neurotoxicity of PAMAM dendrimers, the underlying mechanism of which is poorly-elucidated, poses a far-reaching challenge to their practical applications. In this study, we reported that PAMAM dendrimers induced both cytotoxicity and autophagic flux in a panel of human glioma cell lines. Meanwhile, inhibition of autophagy significantly reversed cell death caused by PAMAM dendrimers, indicating the cytotoxic role of autophagy in neurotoxicity caused by PAMAM dendrimers. Akt/mTOR pathway was most likely to participate in initiation of PAMAM dendrimers-induced autophagy. Moreover, autophagy induced by PAMAM dendrimers might be partially mediated by intracellular ROS generation. Collectively, these data elucidated the critical role of autophagy in neurotoxicity associated with exposure to cationic PAMAM dendrimers in vitro, raising concerns about possible neurotoxic reaction caused by future clinical applications of PAMAM dendrimers and providing potential strategies to ameliorate toxic effects of PAMAM dendrimers. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Effect of poly(amidoamine) dendrimers on the structure and activity of immune molecules.

    Science.gov (United States)

    Lin, Jiansheng; Hua, Wenxi; Zhang, Yi; Li, Chenghua; Xue, Wei; Yin, Jian; Liu, Zonghua; Qiu, Xiaozhong

    2015-02-01

    Poly(amidoamine) (PAMAM) dendrimers are widely used biomedical polymers, which are extensively applied in drug delivery, gene delivery, contrast agent, etc. In these biomedical applications, the bio-safety of the PAMAM dendrimers is a critical issue, which affects not only their toxicity to the host but also the expected in vivo biofunctions of the materials. To clarify the bio-safety of PAMAM dendrimers, the effects of generation 5 PAMAM dendrimers with amine, hydroxyl or carboxyl groups on immune molecules were explored in this work. Specifically, the effect of the PAMAM dendrimers on the secondary structure and conformation of immune molecule γ-globulin was studied by using ultraviolet-visible, fluorescence, and circular dichroism spectroscopies. The effect of the PAMAM dendrimers on complement activation was determined by enzyme-linked immunosorbent assay. Further, the effect of the PAMAM dendrimers on antigen-antibody reaction was studied by using human red blood cell agglutination assay. The results showed that, the PAMAM dendrimers could affect the secondary structure and conformation of γ-globulin, and inhibited complement activation. Generation 5 PAMAM dendrimer with carboxyl group at 10mg/mL impaired red blood cell (RBC) antigen-antibody reaction. From these results, the effects of the PAMAM dendrimers on immune molecules depend on their bulk structure and surface groups. This work provides important information for the immunocompatibility evaluation, preclinical design, and clinical applications of PAMAM dendrimers. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Nucleobase-modified dendrimers as nonviral vectors for efficient and low cytotoxic gene delivery.

    Science.gov (United States)

    Wang, Hui; Wei, Haifeng; Huang, Quan; Liu, Hongmei; Hu, Jingjing; Cheng, Yiyun; Xiao, Jianru

    2015-12-01

    Cationic dendrimers are associated with relatively low transfection efficacy and high toxicity in gene delivery. Surface modification of these dendrimers with functional ligands may resolve these issues. Here, we proposed a novel strategy to prepare surface-engineered dendrimers with high transfection efficacy and low toxicity on transfected cells. Several nucleobase analogues were modified on cationic dendrimers by a facile method. These nucleobase-modified dendrimers show improved transfection efficacy and reduced cytotoxicity compared to unmodified dendrimers on HEK293 and HeLa cells. Efficacy of the most efficient polymer is comparable to that of commercial transfection reagents such as SuperFect, PolyFect, and Lipofectamine 2000. The improved transfection efficacy of dendrimers after nucleobase modification is probably attributed to easier intracellular DNA unpacking and lower cytotoxicity. The results provide a valuable insight to guide the design of efficient and low cytotoxic gene vectors. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2015-05-20

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

  18. Recent Advances in Click Chemistry Applied to Dendrimer Synthesis

    Directory of Open Access Journals (Sweden)

    Mathieu Arseneault

    2015-05-01

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

  19. Impact of Dendrimers on Solubility of Hydrophobic Drug Molecules

    Directory of Open Access Journals (Sweden)

    Sonam Choudhary

    2017-05-01

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

  20. Impact of Dendrimers on Solubility of Hydrophobic Drug Molecules

    Science.gov (United States)

    Choudhary, Sonam; Gupta, Lokesh; Rani, Sarita; Dave, Kaushalkumar; Gupta, Umesh

    2017-01-01

    Adequate aqueous solubility has been one of the desired properties while selecting drug molecules and other bio-actives for product development. Often solubility of a drug determines its pharmaceutical and therapeutic performance. Majority of newly synthesized drug molecules fail or are rejected during the early phases of drug discovery and development due to their limited solubility. Sufficient permeability, aqueous solubility and physicochemical stability of the drug are important for achieving adequate bioavailability and therapeutic outcome. A number of different approaches including co-solvency, micellar solubilization, micronization, pH adjustment, chemical modification, and solid dispersion have been explored toward improving the solubility of various poorly aqueous-soluble drugs. Dendrimers, a new class of polymers, possess great potential for drug solubility improvement, by virtue of their unique properties. These hyper-branched, mono-dispersed molecules have the distinct ability to bind the drug molecules on periphery as well as to encapsulate these molecules within the dendritic structure. There are numerous reported studies which have successfully used dendrimers to enhance the solubilization of poorly soluble drugs. These promising outcomes have encouraged the researchers to design, synthesize, and evaluate various dendritic polymers for their use in drug delivery and product development. This review will discuss the aspects and role of dendrimers in the solubility enhancement of poorly soluble drugs. The review will also highlight the important and relevant properties of dendrimers which contribute toward drug solubilization. Finally, hydrophobic drugs which have been explored for dendrimer assisted solubilization, and the current marketing status of dendrimers will be discussed. PMID:28559844

  1. Novel non-viral gene delivery systems composed of carbosilane dendron functionalized nanoparticles prepared from nano-emulsions as non-viral carriers for antisense oligonucleotides.

    Science.gov (United States)

    Fornaguera, Cristina; Grijalvo, Santiago; Galán, Marta; Fuentes-Paniagua, Elena; de la Mata, Francisco Javier; Gómez, Rafael; Eritja, Ramon; Calderó, Gabriela; Solans, Conxita

    2015-01-15

    The development of novel and efficient delivery systems is often the limiting step in fields such as antisense therapies. In this context, poly(d,l-lactide-co-glycolide) acid (PLGA) nanoparticles have been obtained by a versatile and simple technology based on nano-emulsion templating and low-energy emulsification methods, performed in mild conditions, providing good size control. O/W polymeric nano-emulsions were prepared by the phase inversion composition method at 25°C using the aqueous solution/polysorbate80/[4 wt% PLGA in ethyl acetate] system. Nano-emulsions formed at oil-to-surfactant (O/S) ratios between 10/90-90/10 and aqueous contents above 70 wt%. Nano-emulsion with 90 wt% of aqueous solution and O/S ratio of 70/30 was chosen for further studies, since they showed the appropriate characteristics to be used as nanoparticle template: hydrodynamic radii lower than 50 nm and enough kinetic stability. Nanoparticles, prepared from nano-emulsions by solvent evaporation, showed spherical shape, sizes about 40 nm, negative surface charges and high stability. The as-prepared nanoparticles were functionalized with carbosilane cationic dendrons through a carbodiimide-mediated reaction achieving positively charged surfaces. Antisense oligonucleotides were electrostatically attached to nanoparticles surface to perform gene-silencing studies. These complexes were non-haemolytic and non-cytotoxic at the concentrations required. The ability of the complexes to impart cellular uptake was also promising. Therefore, these novel nanoparticulate complexes might be considered as potential non-viral carriers in antisense therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    Mark Euguenii Martínez-Klimov

    2015-09-01

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

  4. Understanding Peptide Dendrimer Interactions with Model Cell Membrane Mimics

    DEFF Research Database (Denmark)

    Lind, Tania Kjellerup

    membranes or highly conserved motifs, effectively making resistance due to mutations less likely to develop and spread. For this we studied the conditions to form supported lipid bilayers with basic systems and further established a protocol for producing biomimetic bacterial model membranes via the vesicle...... domains or forcing a gel phase membrane pre-equilibrated with dendrimers to undergo a phase transition, enhanced the interaction and led to membrane thinning and dendrimer translocation. These latter models could to a higher degree resemble the heterogenous lateral nanoscale structure of native cell...

  5. Effect of Size, Surface Charge, and Hydrophobicity of Poly(amidoamine) Dendrimers on Their Skin Penetration

    Science.gov (United States)

    Yang, Yang; Sunoqrot, Suhair; Stowell, Chelsea; Ji, Jingli; Lee, Chan-Woo; Kim, Jin Woong; Khan, Seema A.; Hong, Seungpyo

    2012-01-01

    The barrier functions of the stratum corneum (SC) and the epidermal layers present a tremendous challenge in achieving effective transdermal delivery of drug molecules. Although a few reports have shown that poly(amidoamine) (PAMAM) dendrimers are effective skin penetration enhancers, little is known regarding the fundamental mechanisms behind the dendrimer-skin interactions. In this paper, we have performed a systematic study to better elucidate how dendrimers interact with skin layers depending on their size and surface groups. Franz diffusion cells and confocal microscopy were employed to observe dendrimer interactions with full-thickness porcine skin samples. We have found that smaller PAMAM dendrimers (generation 2 (G2)) penetrate the skin layers more efficiently than the larger ones (G4). We have also found that G2 PAMAM dendrimers that are surface modified by either acetylation or carboxylation exhibit increased skin permeation and likely diffuse through an extracellular pathway. In contrast, amine-terminated dendrimers show enhanced cell internalization and skin retention but reduced skin permeation. In addition, conjugation of oleic acid (OA) to G2 dendrimers increases their 1-octanol/PBS partition coefficient, resulting in increased skin absorption and retention. Here we report that size, surface charge, and hydrophobicity directly dictate the permeation route and efficiency of dendrimer translocation across the skin layers, providing a design guideline for engineering PAMAM dendrimers as a potential transdermal delivery vector. PMID:22621160

  6. Coarse-grained simulations of poly(propylene imine) dendrimers in solution

    Science.gov (United States)

    Smeijers, A. F.; Markvoort, A. J.; Pieterse, K.; Hilbers, P. A. J.

    2016-02-01

    The behavior of poly(propylene imine) (PPI) dendrimers in concentrated solutions has been investigated using molecular dynamics simulations containing up to a thousand PPI dendrimers of generation 4 or 5 in explicit water. To deal with large system sizes and time scales required to study the solutions over a wide range of dendrimer concentrations, a previously published coarse-grained model was applied. Simulation results on the radius of gyration, structure factor, intermolecular spacing, dendrimer interpenetration, and water penetration are compared with available experimental data, providing a clear concentration dependent molecular picture of PPI dendrimers. It is shown that with increasing concentration the dendrimer volume diminishes accompanied by a reduction of internalized water, ultimately resulting in solvent filled cavities between stacked dendrimers. Concurrently dendrimer interpenetration increases only slightly, leaving each dendrimer a separate entity also at high concentrations. Moreover, we compare apparent structure factors, as calculated in experimental studies relying on the decoupling approximation and the constant atomic form factor assumption, with directly computed structure factors. We demonstrate that these already diverge at rather low concentrations, not because of small changes in form factor, but rather because the decoupling approximation fails as monomer positions of separate dendrimers become correlated at concentrations well below the overlap concentration.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-06-15

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

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

    African Journals Online (AJOL)

    Purpose: To develop transdermal patches of meloxicam (MLX) using chitosan and hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA) as hydrophilic polymers, polyamido amine (PAMAM) dendrimer as a permeation enhancer, and dibutyl pthalate as a plasticizer. Methods: The patches were prepared by ...

  9. Nanoparticulate platinum films on gold using dendrimer-based wet ...

    Indian Academy of Sciences (India)

    Central Electrochemical Research Institute, Karaikudi 630 006, India. E-mail: kanalaphani@yahoo.com. Abstract. There is a growing interest in devising wet chemical alternatives for ... itating polyamine isolated from diatoms [8,9]. Dendrimers are also excellent hosts for a diverse array of nanoparticles [10–15]. In contrast to ...

  10. Interaction of nucleic acids with carbon nanotubes and dendrimers

    Indian Academy of Sciences (India)

    By using fully atomistic simulations, here we report various aspects of the interactions and binding modes of DNA and small interfering RNA (siRNA) with CNTs, graphene and dendrimers. Our results give a microscopic picture and mechanism of the adsorption of single- and double-strand DNA (ssDNA and dsDNA) on CNT ...

  11. Dendrimers and methods of preparing same through proportionate branching

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Yihua (Bruce); Yue, Xuyi

    2015-09-15

    The present invention provides for monodispersed dendrimers having a core, branches and periphery ends, wherein the number of branches increases exponentially from the core to the periphery end and the length of the branches increases exponentially from the periphery end to the core, thereby providing for attachment of chemical species at the periphery ends without exhibiting steric hindrance.

  12. Dendrimer-coated magnetic particles for radionuclide separation

    NARCIS (Netherlands)

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

    2005-01-01

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

  13. Dendrimer-mediated transfer printing of DNA and RNA mircoarrays

    NARCIS (Netherlands)

    Rozkiewicz, D.I.; Brugman, Wim; Kerkhoven, Ron M.; Ravoo, B.J.; Reinhoudt, David

    2007-01-01

    This paper describes a new method to replicate DNA and RNA microarrays. The technique, which facilitates positioning of DNA and RNA with submicron edge resolution by microcontact printing (μCP), is based on the modification of poly(dimethylsiloxane) (PDMS) stamps with dendrimers (“dendri-stamps”).

  14. 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.

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

    Science.gov (United States)

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

    2017-02-23

    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.

  16. 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

    We report on a simple robust procedure for synthesis of generation-4 poly-(amidoamine) (PAMAM) dendrimers with a precisely core positioned single sulforhodamine B molecule. The labelled dendrimers exhibited high fluorescent quantum yields where the absorbance and fluorescence spectrum of the fluo......We report on a simple robust procedure for synthesis of generation-4 poly-(amidoamine) (PAMAM) dendrimers with a precisely core positioned single sulforhodamine B molecule. The labelled dendrimers exhibited high fluorescent quantum yields where the absorbance and fluorescence spectrum...... of its coupling efficiency). Our dendrimer core-labelling approach could provide a new conceptual basis for improved understanding of dendrimer performance within biological settings...

  17. Multivalent dendrimers at molecular printboards: influence of dendrimer structure on binding strength and stoichiometry and their electrochemically induced desorption

    NARCIS (Netherlands)

    Nijhuis, C.A.; Yu, Fang; Knoll, Wolfgang; Huskens, Jurriaan; Reinhoudt, David

    2005-01-01

    A fundamental understanding of multivalency can have a profound influence on bottom-up nanofabrication. For this purpose, three different types of ferrocenyl (Fc) functionalized dendrimers of generations 1-5 with various spacer groups were adsorbed at self-assembled monolayers (SAMs) of

  18. PAMAM dendrimers: destined for success or doomed to fail? Plain and modified PAMAM dendrimers in the context of biomedical applications.

    Science.gov (United States)

    Labieniec-Watala, Magdalena; Watala, Cezary

    2015-01-01

    PAMAM (polyamidoamine) dendrimers are commonly considered promising polymers that can be successfully used in various biomedical applications. Nevertheless, direct clinical adaptations of plain unmodified PAMAM dendrimers may be limited at present, mainly because of their toxicity, unpredictable behavior in living organisms, unknown bioavailability, biocompatibility or pharmacokinetic profile, problematic therapeutic dose selection, or high cost of production. On the basis of our studies concerning the possible use of unmodified PAMAM dendrimers as the scavengers of glucose and carbonyl stress in animal models of human pathology, as well as considering available literature on experimental data of other researchers, we have prepared the brief critical review of the biomedical activities of these unmodified compounds and their most alluring derivatives, especially in the context of possible future perspectives of PAMAMs. Thus, on the pages of this review, we made an attempt to briefly summarize obstacles, emerging from experimental, technical, and human limitations, that may, to some extent, restrain our belief in a brighter future of plain amine-terminated PAMAM dendrimers. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  19. Visual observation and characterization of fluorescent poly(amido amine) dendrimer in film state.

    Science.gov (United States)

    Saravanan, Govindachetty; Imae, Toyoko

    2011-06-01

    The fluorescent property of PAMAM dendrimers were examined at film state rather than in solution. The O2-treated PAMAM dendrimer displayed strong blue fluorescence due to its conservation of luminance in the film state and diminished its intensity with degas. The fluorescent property of PAMAM dendrimers was utilized as a fluorescent probe on functional patterned substrates for visual observation by a fluorescence microscope. G4 and G4.5 PAMAM dendrimers having peripheral groups of functional amine and carboxylate, respectively, were adsorbed selectively by electrostatic interactions on patterned carboxylic acid and amine terminated surfaces, respectively resulting in strong fluorescent patterns. This suggests the possible application of fluorescent PAMAM dendrimers as a fluorophor for the visualizable reactions. It was confirmed from an X-ray photoelectron spectroscopy that O2 molecules interact with tertiary amine moiety in PAMAM dendrimers but not amide group. These results give us an important support for the principle of fluorescence phenomenon.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-04-15

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

  1. 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

  2. AS1411 Aptamer-Anionic Linear Globular Dendrimer G2-Iohexol Selective Nano-Theranostics

    OpenAIRE

    Mohammadzadeh, Pardis; Cohan, Reza Ahangari; Ghoreishi, Seyedeh Masoumeh; Bitarafan-Rajabi, Ahmad; Ardestani, Mehdi Shafiee

    2017-01-01

    Molecular theranostics is of the utmost interest for diagnosis as well as treatment of different malignancies. In the present study, anionic linear globular dendrimer G2 is employed as a suitable carrier for delivery and AS1411 aptamer is exploited as the targeting agent to carry Iohexol specifically to the human breast cancer cells (MCF-7). Dendrimer G2 was prepared and conjugation of dendrimer and aptamer was carried out thereafter. Based on the data yielded by AFM, morphology of smooth and...

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

    Science.gov (United States)

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

    2006-11-01

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

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

    Science.gov (United States)

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

    2004-10-13

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-11-01

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

  6. Dendrimers as tunable vectors of drug delivery systems and biomedical and ocular applications.

    Science.gov (United States)

    Kalomiraki, Marina; Thermos, Kyriaki; Chaniotakis, Nikos A

    2016-01-01

    Dendrimers are large polymeric structures with nanosize dimensions (1-10 nm) and unique physicochemical properties. The major advantage of dendrimers compared with linear polymers is their spherical-shaped structure. During synthesis, the size and shape of the dendrimer can be customized and controlled, so the finished macromolecule will have a specific "architecture" and terminal groups. These characteristics will determine its suitability for drug delivery, diagnostic imaging, and as a genetic material carrier. This review will focus initially on the unique properties of dendrimers and their use in biomedical applications, as antibacterial, antitumor, and diagnostic agents. Subsequently, emphasis will be given to their use in drug delivery for ocular diseases.

  7. TRANSEPITHELIAL TRANSPORT AND TOXICITY OF PAMAM DENDRIMERS: IMPLICATIONS FOR ORAL DRUG DELIVERY

    Science.gov (United States)

    Sadekar, S.; Ghandehari, H.

    2011-01-01

    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. PMID:21983078

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

    Science.gov (United States)

    Esfand, R; Tomalia, D A.

    2001-04-01

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

  9. Aqueous solubilization of fullerenes using poly(amidoamine) dendrimers bearing cyclodextrin and poly(ethylene glycol).

    Science.gov (United States)

    Kojima, Chie; Toi, Yoko; Harada, Atsushi; Kono, Kenji

    2008-11-19

    Fullerene has a unique structure and notable chemical and physical properties, which have been studied in diverse fields including biological applications. The extremely poor solubility of fullerenes in water limits their usage for biomedical applications. In this study, we synthesized polyamidoamine dendrimers having both beta-cyclodextrin (CD) and poly(ethylene glycol) (PEG) and characterized the resulting dendrimers by (1)H NMR, IR, and gel permeation chromatography. We prepared 2.8 microM of aqueous fullerene solutions using these dendrimers. The clustering effect of CD and PEG at the surface of the dendrimer might be crucial for the solubilization of fullerene.

  10. 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

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

    Science.gov (United States)

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

    2016-04-01

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

  12. 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

    -pyrrolidone dendrimer). The cytotoxic activity of the dendrimer was tested on Chinese hamster fibroblasts (B14), embryonic mouse hippocampal cells (mHippoE-18) and rat liver derived cells (BRL-3A). The same cell lines were used to investigate the influence of pyrrolidone dendrimer on the mitochondrial membrane...

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

    Science.gov (United States)

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

    2016-02-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  15. Catalytically efficient palladium nanoparticles stabilized by "click" ferrocenyl dendrimers.

    Science.gov (United States)

    Ornelas, Cátia; Salmon, Lionel; Aranzaes, Jaime Ruiz; Astruc, Didier

    2007-12-14

    1,2,3-Ferrocenyl triazole ligands generated by click reactions in dendrimers bind Pd(OAc)2 with a systematic one-to-one stoichiometry as monitored by titration using the ferrocenyl redox sensor attached to the triazole ring, and the dendritic PdII complexes formed are best reduced by methanol to form palladium nanoparticles of designed types and sizes that show excellent efficiency and selectivity in olefin hydrogenation.

  16. Controlling Androgen receptor nuclear localization by dendrimer conjugates

    Science.gov (United States)

    Wang, Haoyu

    Androgen Receptor (AR) antagonists, such as bicalutamide and flutamide have been used widely in the treatment of prostate cancer. Although initial treatment is effective, prostate cancer cells often acquire antiandrogen resistance with prolonged treatment. AR over-expression and AR mutations contribute to the development of antiandrogen resistant cancer. Second generation antiandrogens such as enzalutamide are more effective and show reduced AR nuclear localization. In this study, derivatives of PAN52, a small molecule antiandrogen previously developed in our lab, were conjugated to the surface of generation 4 and generation 6 PAMAM dendrimers to obtain antiandrogen PAMAM dendrimer conjugates (APDC). APDCs readily enter cells and associate with AR in the cytoplasm. Due to their large size and positive charge, they can not enter the nucleus, thus retaining AR in the cytoplasm. In addition, APDCs are effective in decreasing AR mediated transcription and cell proliferation. APDC is the first AR antagonists that inhibit DHT-induced nuclear localization of AR. By inhibiting AR nuclear localization, APDC represents a new class of antiandrogens that offer an alternative approach to addressing antiandrogen-resistant prostate cancer. Lysine post-translational modification of AR Nuclear Localization Sequence (NLS) has great impact on AR cellular localization. It is of interest to understand which modifications modulate AR translocation into the nucleus. In this study, we prepared dendrimer-based acetyltransferase mimetic (DATM), DATM is able to catalytically acetylate AR in CWR22Rv1 cells, which will be a useful tool for studying AR modification effect on AR cellular localization. Derivatives of DATM, which transfer other chemical groups to AR, can be prepared similarly, and with more dendrimer based AR modification tools prepared in future, we will be able to understand and control AR cellular localization through AR modification.

  17. Enhanced biological stability of collagen with incorporation of PAMAM dendrimer.

    Science.gov (United States)

    Zhong, Shaoping; Yung, Lin Yue Lanry

    2009-10-01

    The crosslinking methods of collagen using glutaraldehyde (GTA) and 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS) are frequently performed in biomedical applications, but both methods still have their own disadvantages, including the GTA cytotoxicity and low degree of EDC/NHS crosslinking. In this study, we incorporated polyamidoamine (PAMAM) dendrimer with surface amine groups into the two aforementioned crosslinking methods to improve the biostability and structural integrity of collagen. Fifty micromolar of dendrimer concentration was found to have negligible in vitro cytotoxicity and was used for EDC and GTA crosslinking of collagen. The collagenase digestion assay showed that the collagen scaffolds crosslinked in the presence of PAMAM exhibited a higher denature temperature and higher resistance against collagenase digestion compared with their counterparts without dendrimer. Cell proliferation with human conjunctival fibroblasts showed that the incorporation of PAMAM in EDC crosslinking significantly increased the proliferation. All the crosslinked scaffolds also exhibited higher structural stability than the noncrosslinked scaffold. Crosslinking with EDC and PAMAM together yielded substantially higher proliferation and may be a suitable collagen scaffold for biomedical applications.

  18. Blue Light Emitting Polyphenylene Dendrimers with Bipolar Charge Transport Moieties

    Directory of Open Access Journals (Sweden)

    Guang Zhang

    2016-10-01

    Full Text Available Two light-emitting polyphenylene dendrimers with both hole and electron transporting moieties were synthesized and characterized. Both molecules exhibited pure blue emission solely from the pyrene core and efficient surface-to-core energy transfers when characterized in a nonpolar environment. In particular, the carbazole- and oxadiazole-functionalized dendrimer (D1 manifested a pure blue emission from the pyrene core without showing intramolecular charge transfer (ICT in environments with increasing polarity. On the other hand, the triphenylamine- and oxadiazole-functionalized one (D2 displayed notable ICT with dual emission from both the core and an ICT state in highly polar solvents. D1, in a three-layer organic light emitting diode (OLED by solution processing gave a pure blue emission with Commission Internationale de l’Éclairage 1931 CIE xy = (0.16, 0.12, a peak current efficiency of 0.21 cd/A and a peak luminance of 2700 cd/m2. This represents the first reported pure blue dendrimer emitter with bipolar charge transport and surface-to-core energy transfer in OLEDs.

  19. 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.

  20. Binding control and stoichiometry of ferrocenyl dendrimers at a molecular printboard

    NARCIS (Netherlands)

    Nijhuis, C.A.; Huskens, Jurriaan; Reinhoudt, David

    2004-01-01

    Ferrocenyl-functionalized PPI dendrimers of generations 1-5 were adsorbed at self-assembled monolayers of heptathioether-functionalized B-cyclodextrin (B-CD) on gold. The dendrimers form stable supramolecular assemblies at the B-CD host surface having multivalent supramolecular interactions and

  1. Effect of dendrimers on selected enzymes--Evaluation of nano carriers.

    Science.gov (United States)

    Ionov, Maksim; Ihnatsyeu-Kachan, Aliaksei; Michlewska, Sylwia; Shcharbina, Natallia; Shcharbin, Dzmitry; Majoral, Jean-Pierre; Bryszewska, Maria

    2016-02-29

    In the field of nanotechnology, dendrimers represent a new class of highly branched macromolecules that is receiving a stimulating and rising interest. The structural organization of these synthetic macromolecules provides promising opportunities for using them as nano-carriers of drugs or gene material to be delivered to the target cells. For applications of dendrimers as drug carriers, analysis of their specific interactions with biological structures at molecular level is very important. This paper describes the molecular interactions between cationic phosphorus dendrimers of third and fourth generation (CPD G3 and CPD G4) and 3 plasma regulatory proteins, namely aspartate transaminase, alkaline phosphatase and l-lactic dehydrogenase. Dendrimer-protein interactions were studied using spectrofluorimetric, circular dichroism and dynamic light scattering techniques. Their morphology in the presence or absence of dendrimers was examined by transmission electron microscopy. The results suggest that both dendrimers form positively charged complexes with HIV-derived peptides. The circular dichroism spectra show that these dendrimers can significantly change the secondary structure of proteins, indicating formation of protein/dendrimer complexes. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. 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,

  3. Orientational mobility and relaxation spectra of dendrimers: Theory and computer simulation.

    Science.gov (United States)

    Markelov, Denis A; Lyulin, Sergey V; Gotlib, Yuli Y; Lyulin, Alexey V; Matveev, Vladimir V; Lahderanta, Erkki; Darinskii, Anatolij A

    2009-01-28

    The developed theory of the orientational mobility of individual segments of a perfectly branched dendrimer is used to calculate the relaxation spectrum of a dendrimer. Frequency dependences of NMR relaxation 1/T(1) and of the nuclear Overhauser effect have been theoretically calculated from the Brownian dynamics simulation data. The dendrimer segmental orientational mobility is governed by three main relaxation processes: (i) the rotation of the dendrimer as a whole, (ii) the rotation of the dendrimer's branch originated from a given segment, and (iii) the local reorientation of the segment. The internal orientational mobility of an individual dendrimer segment depends only on the topological distance between this segment and the terminal shell of the dendrimer. Characteristic relaxation times of all processes and their contributions to the segmental mobility have been calculated. The influence of the number of generations and the number of the generation shell on the relaxation times has been studied. The correlation between the characteristic times and the calculated relaxation spectrum of the dendrimer has been established.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    Cytotoxicity of cationic amino-terminated PAMAM dendrimer and modified PAMAM-pyrrolidone dendrimer was compared. LDH assay and cell visualization technique were employed. Mouse embryonic hippocampal cells (mHippoE-18) were used. The experiments were performed in FBS-deprived medium. Pyrrolidone...

  5. 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.

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

    Science.gov (United States)

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

    2016-09-28

    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(NH 2 ) 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(NH 2 ) 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(NH 2 ) 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

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

    Directory of Open Access Journals (Sweden)

    Natalia Wrońska

    2015-10-01

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

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

    Science.gov (United States)

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

    2016-12-01

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

  9. Antimicrobial Organometallic Dendrimers with Tunable Activity against Multidrug-Resistant Bacteria.

    Science.gov (United States)

    Abd-El-Aziz, Alaa S; Agatemor, Christian; Etkin, Nola; Overy, David P; Lanteigne, Martin; McQuillan, Katherine; Kerr, Russell G

    2015-11-09

    Multidrug-resistant pathogens are an increasing threat to public health. In an effort to curb the virulence of these pathogens, new antimicrobial agents are sought. Here we report a new class of antimicrobial organometallic dendrimers with tunable activity against multidrug-resistant Gram-positive bacteria that included methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. Mechanistically, these redox-active, cationic organometallic dendrimers induced oxidative stress on bacteria and also disrupted the microbial cell membrane. The minimum inhibitory concentrations, which provide a quantitative measure of the antimicrobial activity of these dendrimers, were in the low micromolar range. AlamarBlue cell viability assay also confirms the antimicrobial activity of these dendrimers. Interestingly, these dendrimers were noncytotoxic to epidermal cell lines and to mammalian red blood cells, making them potential antimicrobial platforms for topical applications.

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

    Science.gov (United States)

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

    2016-01-19

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

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

    Science.gov (United States)

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

    2016-09-10

    Dendrimers have called the attention of scientists in the area of drug and gene delivery over the last two decades for their versatility, complexity and multibranching properties. Some strategies for optimizing drug pharmacokinetics and site-specific targeting using dendrimers have been proposed. Among them, those related to treating and managing ocular diseases are of special interest. Ocular therapies suffer from significant disadvantages, including frequent administration, poor penetration and/or rapid elimination. This review provides an overview of the recent and promising progress in the dendrimers field, focusing on both the anterior and posterior segments of the eye ocular targets, the use of dendrimers as a strategy for overcoming obstacles to the traditional treatment of ocular diseases and an outlook on future directions. Finally, a first approach to ocular safety with dendrimers is intended that accounts for the state-of-the-art science to date. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Wrońska, Natalia; Felczak, Aleksandra; Zawadzka, Katarzyna; Poszepczyńska, Martyna; Różalska, Sylwia; Bryszewska, Maria; Appelhans, Dietmar; Lisowska, Katarzyna

    2015-10-23

    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.

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

    Science.gov (United States)

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

    2014-01-01

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

  14. PEGylated PAMAM dendrimers: Enhancing efficacy and mitigating toxicity for effective anticancer drug and gene delivery.

    Science.gov (United States)

    Luong, Duy; Kesharwani, Prashant; Deshmukh, Rahul; Mohd Amin, Mohd Cairul Iqbal; Gupta, Umesh; Greish, Khaled; Iyer, Arun K

    2016-10-01

    Poly(amidoamine) dendrimers (PAMAM) are well-defined, highly branched, nanoscale macromolecules with numerous active amine groups on the surface. PAMAM dendrimer can enhance the solubility of hydrophobic drugs, and with numerous reactive groups on the surface PAMAM dendrimer can be engineered with various functional groups for specific targeting ability. However, in physiological conditions, these amine groups are toxic to cells and limit the application of PAMAM. In the recent years, polyethylene glycol (PEG) conjugation has been the most widely used approach to reduce the toxicity of the active group on dendrimer surface. PEG molecules are known to be inert, non-immunogenic, and non-antigenic with a significant water solubility. PEGylated PAMAM-mediated delivery could not only overcome the limitations of dendrimer such as drug leakage, immunogenicity, hemolytic toxicity, systemic cytotoxicity but they also have the ability to enhance the solubilization of hydrophobic drugs and facilitates the potential for DNA transfection, siRNA delivery and tumor targeting. This review focuses on the recent developments on the application and influence of PEGylation on various biopharmaceutical properties of PAMAM dendrimers. It is well established that dendrimers have demonstrated promising potentials for drug delivery. However, the inherent toxicity poses challenges for its clinical translation. In this regard, PEGylation has helped mitigate some of the toxicity concerns of dendrimers and have paved the way forward for testing its translational potentials. The review is a collection of articles demonstrating the utility of PEGylation of the most studied PAMAM dendrimers. To our knowledge, this is a first such attempt to draw reader's attention, specifically, towards PEGylated PAMAM dendrimers. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  15. Structure-activity relationship of dendrimers engineered with twenty common amino acids in gene delivery.

    Science.gov (United States)

    Wang, Fei; Hu, Ke; Cheng, Yiyun

    2016-01-01

    Systematic explorations on the structure-activity relationship of surface-engineered dendrimers are essential to design high efficient and safe gene vectors. The chemical diversity of residues in naturally occurring amino acids allows us to generate a library of dendrimers with various surface properties. Here, we synthesized a total number of 40 dendrimers engineered with the twenty common amino acids and investigated their performances in gene delivery. The results show that gene transfection efficacy of the synthesized materials depends on both the type of amino acid and the conjugation ratio. Dendrimers engineered with cationic and hydrophobic amino acids possess relatively higher transfection efficacies. Engineering dendrimers with cationic amino acids such as arginine and lysine facilitates polyplex formation and cellular uptake, with histidine improves endosomal escape of the polyplexes, and with hydrophobic amino acids such as tyrosine and phenylalanine modulates the balance between hydrophobicity and hydrophilicity on dendrimer surface, which is beneficial for efficient cellular internalization. Dendrimers engineered with anionic or hydrophilic amino acids show limited transfection efficacy due to poor DNA binding capacity and/or limited cellular uptake. In the aspect of cytotoxicity, dendrimers engineered with arginine, lysine, tyrosine, phenylalanine and tryptophan show much higher cytotoxicity than other engineered dendrimers. These results are helpful for us to tailor the surface chemistry of dendrimers for efficient gene delivery. Cationic polymers such as dendrimers were widely used as gene vectors but are limited by relatively low delivery efficacy and high toxicity. To achieve efficient and low toxic gene delivery, the polymers were modified with various ligands. However, these ligand-modified polymers in gene delivery are reported by independent researchers using different polymer scaffolds and cell lines. It is hard to provide structure

  16. Amino acid-functionalized dendrimers with heterobifunctional chemoselective peripheral groups for drug delivery applications

    Science.gov (United States)

    Navath, RS; Menjoge, AR; Wang, B; Romero, R; Kannan, S; Kannan, RM

    2013-01-01

    Dendrimers have emerged as multifunctional carriers for targeted drug delivery, gene delivery and imaging. Improving the functional versatility at the surface for carrying multiple conjugation reactions is becoming vital. Typically, generation four polyamidoamine (G4-PAMAM) dendrimers bear ~64 symmetrical end groups, often requiring different spacers to conjugate various functional groups (drugs and targeting moieties), increasing the synthetic steps. In the present study, a simple one-step synthesis to convert each symmetrical end group of G4-PAMAM dendrimers into two reactive, distinct orthogonal and chemoselective groups is described. A near-complete end-capping of the dendrimers (87–93%) with amino acids results in heterobifunctional G4-PAMAM dendrimers bearing a very high (≥ 110) diverse peripheral end groups (OH+NHBoc, OH+COOMe, SH+NHBoc, and COOH+NHBoc). Postfunctionalization ability of these dendrimers was evaluated. The heterbifunctional groups at the dendrimer periphery could be chemoselectively conjugated to multiple moieties such as drugs (indomethacin and dexamethasone) and drugs and imaging agents (dexamethasone and FITC). These conjugations could be achieved in immediate succession without functional group conversions, eliminating the additional elaborate synthetic steps traditionally required to append specific linkers. Furthermore, one of the two functional handles at periphery was used to develop in situ forming hydrogels, whereas the other handle could be used for conjugating the drugs (e.g., dexamethasone). The heterobifunctional dendrimers with either “NH2 or SH (thiopyridyl protected form)” terminations showed in situ hydrogel formation by cross-linking with N-hydroxysuccinimide or thiol-terminated multiarm polyethylene glycol (20 kDa). The choice of amino acids as versatile linkers would enable biocompatible dendrimer scaffolds for use in drug delivery. ζ-potential measurements showed drastic lowering of the charge on G4-PAMAM-NH2

  17. Effect of electron donating groups on polyphenol-based antioxidant dendrimers.

    Science.gov (United States)

    Lee, Choon Young; Nanah, Cyprien N; Held, Rich A; Clark, Amanda R; Huynh, Uyen G T; Maraskine, Marina C; Uzarski, Rebecca L; McCracken, John; Sharma, Ajit

    2015-04-01

    Numerous studies have reported the beneficial effects of antioxidants in human diseases. Among their biological effects, a majority of antioxidants scavenge reactive radicals in the body, thereby reducing oxidative stress that is associated with the pathogenesis of many diseases. Antioxidant dendrimers are a new class of potent antioxidant compounds reported recently. In this study, six polyphenol-based antioxidant dendrimers with or without electron donating groups (methoxy group) were synthesized in order to elucidate the influence of electron donating groups (EDG) on their antioxidant activities. Syringaldehyde (2 ortho methoxy groups), vanillin (1 ortho methoxy group), and 4-hydroxybenzaldehyde (0 methoxy group) were derivatized with propargylamine to form building blocks for the dendrimers. All the six dendrimers contain polyether cores, which were synthesized by attaching pentaerythritol and methyl α-d-glucopyranoside to in-house prepared spacer units. To prepare generation 1 antioxidant dendrimers, microwave energy and granulated metallic copper catalyst were used to link the cores and building blocks together via alkyne-azide 1,3-cycloaddition click chemistry. These reaction conditions resulted in high yields of the target dendrimers that were free from copper contamination. Based on DPPH antioxidant assay, antioxidant dendrimers decorated with syringaldehyde and vanillin exhibited over 70- and 170-fold increase in antioxidant activity compared to syringaldehyde and vanillin, respectively. The antioxidant activity of dendrimers increased with increasing number of EDG groups. Similar results were obtained when the dendrimers were used to protect DNA and human LDL against organic carbon and nitrogen-based free radicals. In addition, the antioxidant dendrimers did not show any pro-oxidant activity on DNA in the presence of physiological amounts of copper. Although the dendrimers showed potent antioxidant activities against carbon and nitrogen free radicals

  18. Influence of fourth generation poly(propyleneimine) dendrimers on blood cells.

    Science.gov (United States)

    Ziemba, Barbara; Halets, Inessa; Shcharbin, Dzmitry; Appelhans, Dietmar; Voit, Brigitte; Pieszynski, Ireneusz; Bryszewska, Maria; Klajnert, Barbara

    2012-11-01

    Dendrimers provide many exciting opportunities for potential biomedical applications. However, owing to their positively charged surfaces, poly(propyleneimine) (PPI) dendrimers show toxic and haemolytic activities. One of the methods for masking the peripheral cationic groups is to modify them using carbohydrate residues. In this study, three types of the fourth generation PPI dendrimers-uncoated (PPI-g4), approximately 35% maltotriose (Mal-III)-coated (PPI-g4-OS), and approximately 90% Mal-III-coated (PPI-g4-DS) were investigated by assessing their effects on red blood cell (RBC) haemolysis in samples of pure RBCs, RBCs in the presence of human serum albumin (HSA) or human plasma, and RBCs in whole blood. Lymphocyte proliferation and platelet (PLT) aggregation were also studied in the presence of various concentrations of dendrimers. Although all dendrimers examined affected all the blood cells studied, the unmodified PPI-g4 had the most damaging effect. It caused high RBC haemolysis rates and PLT aggregation and greatly inhibited lymphocyte proliferation. These effects were caused by the cationic surface of this polymer. The modification of PPI-g4 with Mal-III reduced the effect of the dendrimer on all blood cells. The presence of HSA or plasma in the buffer containing the RBCs or RBC in whole blood significantly decreased the extent of dendrimer-driven haemolysis. Copyright © 2012 Wiley Periodicals, Inc.

  19. Shape-persistent and adaptive multivalency: rigid transgeden (TGD) and flexible PAMAM dendrimers for heparin binding.

    Science.gov (United States)

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

    2014-07-28

    This study investigates transgeden (TGD) dendrimers (polyamidoamine (PAMAM)-type dendrimers modified with rigid polyphenylenevinylene (PPV) cores) and compares their heparin-binding ability with commercially available PAMAM dendrimers. Although the peripheral ligands are near-identical between the two dendrimer families, their heparin binding is very different. At low generation (G1), TGD outperforms PAMAM, but at higher generation (G2 and G3), the PAMAMs are better. Heparin binding also depends strongly on the dendrimer/heparin ratio. We explain these effects using multiscale modelling. TGD dendrimers exhibit "shape-persistent multivalency"; the rigidity means that small clusters of surface amines are locally well optimised for target binding, but it prevents the overall nanoscale structure from rearranging to maximise its contacts with a single heparin chain. Conversely, PAMAM dendrimers exhibit "adaptive multivalency"; the flexibility means individual surface ligands are not so well optimised locally to bind heparin chains, but the nanostructure can adapt more easily and maximise its binding contacts. As such, this study exemplifies important new paradigms in multivalent biomolecular recognition. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Clustering Small Dendrimers into Nanoaggregates for Efficient DNA and siRNA Delivery with Minimal Toxicity.

    Science.gov (United States)

    Liu, Chongyi; Shao, Naimin; Wang, Yitong; Cheng, Yiyun

    2016-03-09

    Cationic dendrimers are widely used as nonviral gene vectors, however, current gene materials based on dendrimers are either little effective or too toxic on the transfected cells. Here, a facile strategy is presented to prepare high efficient dendrimers with low transfection toxicity. Small dendrimers with 2 nm are clustered into nanoaggregates (≈100 nm) via phenylboronic acid modification and the self-assembled materials enable efficient DNA and siRNA delivery on several cell lines. The clustered nanostructures can disassemble into small dendrimers in acidic conditions thus exerting significantly less toxicity on the transfected cells. Further structure-function relationship studies reveal that both the phenyl group and boronic acid group play essential roles in the self-assembly and gene delivery processes. The transfection efficacy of phenylboronic acid-modified dendrimers can be down-regulated by blocking the boronic acid groups on dendrimers with diols or degrading the groups with hydrogen peroxide. This study provides a facile strategy in the development of efficient and biocompatible gene vectors based on low molecular weight polymers and clearly demonstrates the structure-function relationship of phenylboronic acid-modified polymers in gene delivery. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. 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.

  2. Transepithelial Transport of PAMAM Dendrimers across Isolated Rat Jejunal Mucosae in Ussing Chambers

    Science.gov (United States)

    2015-01-01

    Oral delivery remains a challenge for poorly permeable hydrophilic macromolecules. Poly(amido amine) (PAMAM) dendrimers have shown potential for their possible oral delivery. Transepithelial transport of carboxyl-terminated G3.5 and amine-terminated G4 PAMAM dendrimers was assessed using isolated rat jejunal mucosae mounted in Ussing chambers. The 1 mM FITC-labeled dendrimers were added to the apical side of mucosae. Apparent permeability coefficients (Papp) from the apical to the basolateral side were significantly increased for FITC when conjugated to G3.5 PAMAM dendrimer compared to FITC alone. Minimal signs of toxicity were observed when mucosae were exposed to both dendrimers with respect to transepithelial electrical resistance changes, carbachol-induced short circuit current stimulation, and histological changes. [14C]-mannitol fluxes were not altered in the presence of 1 mM dendrimers, suggesting that the paracellular pathway was not affected at this concentration in this model. These results give insight into the mechanism of PAMAM dendrimer transepithelial rat jejunal transport, as well as toxicological considerations important for oral drug delivery. PMID:24992090

  3. Development of a Topical Resveratrol Formulation for Commercial Applications Using Dendrimer Nanotechnology.

    Science.gov (United States)

    Pentek, Tyler; Newenhouse, Eric; O'Brien, Brennin; Chauhan, Abhay Singh

    2017-01-14

    Resveratrol (RSV) is well known for its anti-oxidant and anti-aging properties. However, resveratrol is insoluble in water and has stability issues. Recently, efforts were placed to prepare a resveratrol-based advanced anti-aging topical product but it contains harsh organic solvents and oils that could be harmful to the human body and the environment. Hence, we propose the use of a multifunctional dendrimer to solve the solubility and stability issues of resveratrol. A dendrimer-resveratrol complex was prepared, optimized and tested for solubility enhancement, stability in solution and cream dosage forms. We have also developed a high performance liquid chromatography method to measure the resveratrol within the final product. PAMAM dendrimers increased the solubility and stability of resveratrol in water and semisolid dosage forms. Therefore, this product would be water based 'green' formulation devoid of harsh organic solvents and oils and can be safely applied to the skin. Additionally, we have shown that the dendrimer helped to increase overall RSV loading and skin penetration of resveratrol. The dendrimer-RSV formulation was successfully scaled up towards commercialization. Dendrimer with RSV has led to an innovation in anti-aging cream and solutions that could be commercially marketed. Dendrimer-RSV complex could also be added to other product forms for additional purposes and applications.

  4. Structure-function relationship of PAMAM dendrimers as robust oil dispersants.

    Science.gov (United States)

    Geitner, Nicholas K; Wang, Bo; Andorfer, Rachel E; Ladner, David A; Ke, Pu Chun; Ding, Feng

    2014-11-04

    PAMAM dendrimers have recently been investigated as efficient and biocompatible oil dispersants utilizing their encapsulation capacity; however, their high cationic charge density has been shown to be cytotoxic. It is therefore imperative to mitigate cationic charge-induced toxicity and understand the effects of such changes. Presented here is a synergistic experimental and computational approach to examine the effects of varying terminal surface charge on the capacity of dendrimers to disperse model liner, polycyclic aromatic, and hybrid hydrocarbons. Uncharged dendrimers collapse by forming intramolecular hydrogen bonds, which reduce the hosting capability. On the other hand, changing the surface charges from positive to negative greatly shifts the pKa of tertiary amines of the PAMAM dendrimer interior. As a result, the negatively charged dendrimers have a significant percentage of tertiary amines protonated, ∼30%. This unexpected change in the interior protonation state causes electrostatic interactions with the anionic terminal groups, leading to contraction and a marked decrease in hydrocarbon hosting capacity. The present work highlights the robust nature of dendrimer oil dispersion and also illuminates potentially unintended or unanticipated effects of varying dendrimer surface chemistry on their encapsulation or hosting efficacy, which is important for their environmental, industrial, and biomedical applications.

  5. Tautomeric forms of PPI dendrimers functionalized with 4-(4 Prime -ethoxybenzoyloxy)salicylaldehyde chromophores

    Energy Technology Data Exchange (ETDEWEB)

    Franckevicius, M., E-mail: marius.franckevicius@ftmc.lt [Institute of Physics, Center for Physical Sciences and Technology, Savanoriu Ave. 231, LT-02300 Vilnius (Lithuania); Vaisnoras, R. [Liquid Crystals Laboratory, Lithuanian Educological University, Studentu 39, LT-08106 Vilnius (Lithuania); Marcos, M.; Serrano, J.L. [Facultad de Ciencias de Materiales de Aragon, Universidad de Zaragoza, Pedro Cerbuna 12, E-50009 Zaragoza (Spain); Gruodis, A.; Galikova, N.; Gulbinas, V. [Institute of Physics, Center for Physical Sciences and Technology, Savanoriu Ave. 231, LT-02300 Vilnius (Lithuania); Department of General Physics and Spectroscopy, Faculty of Physics, Vilnius University, Sauletekio 9, LT-10222 Vilnius (Lithuania)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer SA chromophore groups are formed by bonding terminal groups to PPI dendrimers. Black-Right-Pointing-Pointer SA chromophore groups reveal four most stable tautomeric forms. Black-Right-Pointing-Pointer Tautomeric properties of SA groups depend on the dendrimer generation and solvent. Black-Right-Pointing-Pointer Aggregation of SA chromophores facilitates formation of the trans-keto tautomers. Black-Right-Pointing-Pointer Fluorescence of PPI SA dendrimers is attributed to n{pi}{sup Asterisk-Operator} states of keto tautomers. -- Abstract: Bonding of the promesogenic unit derived from 4-(4 Prime -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 n{pi}{sup Asterisk-Operator} states of keto tautomers which may also be formed from excited enol tautomers.

  6. Cholesterol-conjugated supramolecular assemblies of low generations polyamidoamine dendrimers for enhanced EGFP plasmid DNA transfection

    Energy Technology Data Exchange (ETDEWEB)

    Golkar, Nasim; Samani, Soliman Mohammadi; Tamaddon, Ali Mohammad, E-mail: amtamadon@gmail.com [Shiraz University of Medical Sciences, Department of Pharmaceutics, School of Pharmacy (Iran, Islamic Republic of)

    2016-05-15

    Aimed to prepare an enhanced gene delivery system with low cytotoxicity and high transfection efficiency, various cholesterol-conjugated derivates of low generation polyamidoamine (PAMAM) dendrimers were prepared. The conjugates were characterized by TNBS assay, FTIR, and {sup 1}H-NMR spectroscopy. Self-assembly of the dendrimer conjugates (G1-Chol, G2-Chol, and G3-Chol) was investigated by pyrene assay. Following formation of the complexes between enhanced green fluorescence protein plasmid and the dendrimer conjugates at various N (primary amine)/P (phosphate) mole ratios, plasmid condensation, biologic stability, cytotoxicity, and protein expression were investigated. The conjugates self-assembled into micellar dispersions with the critical micelle concentration values (<50 µg/ml) depending on the dendrimer generation and cholesterol/amine mole ratio. Cholesterol conjugation resulted in higher resistance of the condensed plasmid DNA in a competition assay with heparin sulfate. Also, the transfection efficiency was determined higher for the cholesterol conjugates than unmodified dendrimers in HepG2 cells, showing the highest for G2-Chol at 40 % degree of cholesterol modification (G2-Chol{sub 40 %}) among various dendrimer generations. Interestingly, such conjugate showed a complete protection of plasmid against serum nucleases. Our results confirmed that the cholesterol conjugation to PAMAM dendrimers of low generations bearing little cytotoxicity improves their several physicochemical and biological characteristics required for an enhanced delivery of plasmid DNA into cells.

  7. Development of a Topical Resveratrol Formulation for Commercial Applications Using Dendrimer Nanotechnology

    Directory of Open Access Journals (Sweden)

    Tyler Pentek

    2017-01-01

    Full Text Available Resveratrol (RSV is well known for its anti-oxidant and anti-aging properties. However, resveratrol is insoluble in water and has stability issues. Recently, efforts were placed to prepare a resveratrol-based advanced anti-aging topical product but it contains harsh organic solvents and oils that could be harmful to the human body and the environment. Hence, we propose the use of a multifunctional dendrimer to solve the solubility and stability issues of resveratrol. A dendrimer-resveratrol complex was prepared, optimized and tested for solubility enhancement, stability in solution and cream dosage forms. We have also developed a high performance liquid chromatography method to measure the resveratrol within the final product. PAMAM dendrimers increased the solubility and stability of resveratrol in water and semisolid dosage forms. Therefore, this product would be water based ‘green’ formulation devoid of harsh organic solvents and oils and can be safely applied to the skin. Additionally, we have shown that the dendrimer helped to increase overall RSV loading and skin penetration of resveratrol. The dendrimer-RSV formulation was successfully scaled up towards commercialization. Dendrimer with RSV has led to an innovation in anti-aging cream and solutions that could be commercially marketed. Dendrimer-RSV complex could also be added to other product forms for additional purposes and applications.

  8. Promoting siRNA delivery via enhanced cellular uptake using an arginine-decorated amphiphilic dendrimer

    Science.gov (United States)

    Liu, Xiaoxuan; Liu, Cheng; Zhou, Jiehua; Chen, Chao; Qu, Fanqi; Rossi, John J.; Rocchi, Palma; Peng, Ling

    2015-02-01

    RNA interference (RNAi) with small interfering RNA (siRNA) is expected to offer an attractive means to specifically and efficiently silence disease-associated genes for treating various diseases provided that safe and efficient delivery systems are available. In this study, we have established an arginine-decorated amphiphilic dendrimer composed of a hydrophobic alkyl chain and a hydrophilic PAMAM dendron bearing arginine terminals as nonviral vector for siRNA delivery. Indeed, this dendrimer proved to be very effective at delivering siRNAs in human prostate cancer PC-3 cells and in human hematopoietic CD34+ stem cells, leading to improved gene silencing compared to the corresponding nonarginine decorated dendrimer. Further investigation confirmed that this dendrimer was granted with the capacity to form stable nanoparticles with siRNA and significantly enhance cellular uptake of siRNA. In addition, this dendrimer revealed no discernible cytotoxicity. All these findings demonstrate that decoration of the dendrimer surface with arginine residues is indeed a useful strategy to improve the delivery ability of dendrimers.

  9. Poly(amidoamine) dendrimers as ophthalmic vehicles for ocular delivery of pilocarpine nitrate and tropicamide.

    Science.gov (United States)

    Vandamme, Th F; Brobeck, L

    2005-01-20

    The purpose of this study was to determine the influence of a controlled incremental increase in size, molecular weight and number of amine, carboxylate and hydroxyl surface groups in several series of poly(amidoamine) (PAMAM) dendrimers for controlled ocular drug delivery. The duration of residence time was evaluated after solubilization of several series of PAMAM dendrimers (generations 1.5 and 2-3.5 and 4) in buffered phosphate solutions containing 2 per thousand (w/v) of fluorescein. The New Zealand albino rabbit was used as an in vivo model for qualitative and quantitative assessment of ocular tolerance and retention time after a single application of 25 microl of dendrimer solution to the eye. The same model was also used to determine the prolonged miotic or mydriatic activities of dendrimer solutions, some containing pilocarpine nitrate and some tropicamide, respectively. Residence time was longer for the solutions containing dendrimers with carboxylic and hydroxyl surface groups. No prolongation of remanence time was observed when dendrimer concentration (0.25-2%) increased. The remanence time of PAMAM dendrimer solutions on the cornea showed size and molecular weight dependency. This study allowed novel macromolecular carriers to be designed with prolonged drug residence time for the ophthalmic route.

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

    Directory of Open Access Journals (Sweden)

    Alessandra Nogueira Santos

    2010-03-01

    Full Text Available The utilization of nanostructured materials for development of biosensors is a growing field in medical diagnostics. In this work a glucose biosensor based on bioactive polyglycerol (PGLD and chitosan dendrimers (CHD was developed. PGLD and CHD were bioconjugated with the enzyme glucose oxidase (GOx to obtain dendrimers with glucose sensing properties. Polyaniline nanotubes (PANINT´s were used as electron mediator due to their high ability to promote electron-transfer reactions involving GOx. The PGLD-GOx and CHD-GOx were entrapped in PANINT´s during template electrochemical polymerization of aniline. The prepared PGLD-GOx/PANINT´s and CHD-GOx/PANINT´s biosensors exhibit a strong and stable amperometric response to glucose even at a low potential of +100 mV. The based PGLD-GOx/PANINT´s and CHD-GOx/PANINT´s biosensors showed a good performance in glucose concentrations range in human blood. A comparison of the sensitivities to glucose showed that both biosensors have a linearity range between 0.02 and 10 mM, though PGLD-GOx/PANINT´s is more sensitive (10.41 vs. 7.04 nA.mM-1. The difference in the biosensor behavior and the high sensitivity of the PGLD-GOx/PANINT´s may be due to the specific organization of GOx layer at surface of the modifier macromolecule PGLD and their distribution in PANINT´s. The enzyme affinity for the substrate, K Mapp remains quite good after GOx immobilization on PGLD and CHD dendrimers and entrapment of the bioconjugates in PANINT´s.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-03-15

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

  12. The Debye light scattering equation's scaling relation reveals the purity of synthetic dendrimers

    Science.gov (United States)

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

    2016-03-01

    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.

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

    Directory of Open Access Journals (Sweden)

    R. Ritawidya1,2

    2012-12-01

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

  14. Aminolevulinic acid dendrimers in photodynamic treatment of cancer and atheromatous disease.

    Science.gov (United States)

    Rodriguez, L; Vallecorsa, P; Battah, S; Di Venosa, G; Calvo, G; Mamone, L; Sáenz, D; Gonzalez, M C; Batlle, A; MacRobert, A J; Casas, A

    2015-09-26

    The use of endogenous protoporphyrin IX after administration of 5-aminolaevulinic acid (ALA) has led to many applications in photodynamic therapy (PDT). We have previously reported that the conjugation of ALA dendrimers enhances porphyrin synthesis. The first aim of this work was to evaluate the ability of ALA dendrimers carrying 6 and 9 ALA residues (6m-ALA and 9m-ALA) to photosensitise cancer cells. For this aim, we employed LM3 mammary carcinoma cells. In these tumour cells, at low concentrations porphyrin synthesis from dendrimers was higher compared to ALA, whereas at high concentrations, porphyrin synthesis was similar from both compounds. Topical application of ALA dendrimers on the skin overlying a subcutaneous LM3 implanted tumour showed no diffusion of the molecules either to distant skin sites or to the adjacent tumour, suggesting a promising use of the ALA macromolecules in superficial cancer models. As a second objective, we proposed the use of ALA-dendrimers in vascular PDT for the treatment of atherosclerosis. Thus, we focused our studies on ALA-dendrimer's selectivity towards macrophages in comparison with endothelial cells. For this aim we employed Raw 264.7 macrophages and HMEC-1 microvasculature cells. Porphyrin synthesis induced in macrophages by 6m-ALA and 9m-ALA (3 h, 0.025 mM) was 6 and 4.6 times higher respectively compared to the endothelial cell line, demonstrating the high affinity of ALA dendrimers for macrophages. On the other hand, ALA employed at low concentrations was slightly selective (1.7-fold) for macrophages. Inhibition studies suggested that ALA dendrimer uptake in macrophages is mainly mediated by caveloae-mediated endocytosis. Our main conclusion is that in addition to being promising molecules in PDT of superficial cancer, ALA dendrimers may also find applications in vascular PDT, since in vitro they showed selectivity to the macrophage component of the atheromatous plaque, as compared to the vascular endothelium.

  15. Charge Affects the Oral Toxicity of Poly(amido amine) Dendrimers

    Science.gov (United States)

    Thiagarajan, Giridhar; Greish, Khaled; Ghandehari, Hamidreza

    2013-01-01

    Poly(amido amine) (PAMAM) dendrimers have been evaluated for the influence of surface functionality and size on the epithelial barrier of the gut with the goal of identifying safe carriers that can be used for oral drug delivery. Limited studies are conducted to date however to assess the toxicity of PAMAM dendrimers in vivo when administered by the oral route. The goal of this research was to conduct an oral acute toxicity study of PAMAM dendrimers as a function of size and charge in immune competent CD-1 mice. Maximum tolerated doses (MTD) of PAMAM dendrimers as a function of size and surface functionality were established and clinical signs of toxicity monitored. Results demonstrate that positively charged dendrimers caused more toxicity whereas their anionic counterparts were tolerated at ten times higher doses. Severe signs of toxicity observed for large (G7) cationic amine- or hydroxyl-terminated dendrimers include hemobilia and spleenomegaly. The MTD for these dendrimers ranged from 30mg/kg to 200mg/kg. Anionic G6.5 or smaller molecular weight carboxyl-, amine- or hydroxyl-terminated dendrimers (G3.5-COOH, G4-NH2, G4-OH) on the other hand were tolerated at doses of upto 500mg/kg (300mg/kg in some cases) with minimal or no signs of toxicity. Establishing the MTD of orally delivered PAMAM dendrimers and the influence of surface functionality and size on toxicity, aids in the rational design of PAMAM-drug conjugates for oral drug delivery applications. PMID:23419816

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

    Science.gov (United States)

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

    2016-07-21

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

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    Chevelle A. Cason

    2012-01-01

    Full Text Available 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 accuracy. In addition, the capture assay platform shows a promising approach to patterning dendrimers for nanotechnology applications.

  19. 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....

  20. Bioinspired therapeutic dendrimers as efficient peptide drugs based on supramolecular interactions for tumor inhibition.

    Science.gov (United States)

    Zhang, Xiao; Zhang, Zhijun; Xu, Xianghui; Li, Yunkun; Li, Yachao; Jian, Yeting; Gu, Zhongwei

    2015-03-27

    Bioinspired tryptophan-rich peptide dendrimers (TRPDs) are designed as a new type of dendritic peptide drugs for efficient tumor therapy. The TRPDs feature a precise molecular structure and excellent water solubility and are obtained in a facile process. Based on the unique features of peptide dendrimers, including highly branched structures, abundant terminal groups, and globular-protein-like architectures, the therapeutic dendrimers show significant supramolecular interactions with DNA through the tryptophan residues (indole rings and amino groups). Further experimental results indicate that TRPDs are efficient antitumor agents both in vitro and in vivo. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-01-01

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

  2. Electron injection from graphene quantum dots to poly(amido amine) dendrimers

    Science.gov (United States)

    Lin, T. N.; Inciong, M. R.; Santiago, S. R.; Kao, C. W.; Shu, G. W.; Yuan, C. T.; Shen, J. L.; Yeh, J. M.; Chen-Yang, Y. W.

    2016-04-01

    The steady-state and time-resolved photoluminescence (PL) are used to study the electron injection from graphene quantum dots (GQDs) to poly(amido amine) (PAMAM) dendrimers. The PL is enhanced by depositing GQDs on the surfaces of the PAMAM dendrimers. The maximum enhancement of PL with a factor of 10.9 is achieved at a GQD concentration of 0.9 mg/ml. The dynamics of PL in the GQD/PAMAM composite are analyzed, evidencing the existence of electron injection. On the basis of Kelvin probe measurements, the electron injection from the GQDs to the PAMAM dendrimers is accounted for by the work function difference between them.

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

    Directory of Open Access Journals (Sweden)

    Eric G. Morales-Espinoza

    2010-04-01

    Full Text Available Dendrons with ferrocenyl ended groups joined by styryl moieties were attached to a porphyrin core. All the dendrons used for dendrimer synthesis showed trans configuration. The chemical structure of the first generation dendron was confirmed by X-ray crystallographic studies. The structure of the synthesized dendrimers was confirmed by 1H- and 13C-NMR, electrospray mass spectrometry and elemental analysis. Cubic non-linear optical behavior of the ferrocene and porphyrin-containing dendrimers was studied in solid thin films by THG Maker-Fringe technique at 1,260 nm.

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

    Science.gov (United States)

    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 accuracy. In addition, the capture assay platform shows a promising approach to patterning dendrimers for nanotechnology applications.

  5. Organometallic Silicon-Containing Dendrimers and Their Electrochemical Applications

    Science.gov (United States)

    Cuadrado, Isabel

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

  6. Synthetic Strategies towards Fullerene-Rich Dendrimer Assemblies

    Directory of Open Access Journals (Sweden)

    Jean-François Nierengarten

    2012-02-01

    Full Text Available The sphere-shaped fullerene has attracted considerable interest not least due to the peculiar electronic properties of this carbon allotrope and the fascinating materials emanating from fullerene-derived structures. The rapid development and tremendous advances in organic chemistry allow nowadays the modification of C60 to a great extent by pure chemical means. It is therefore not surprising that the fullerene moiety has also been part of dendrimers. At the initial stage, fullerenes have been examined at the center of the dendritic structure mainly aimed at possible shielding effects as exerted by the dendritic environment and light-harvesting effects due to multiple chromophores located at the periphery of the dendrimer. In recent years, also many research efforts have been devoted towards fullerene-rich nanohybrids containing multiple C60 units in the branches and/or as surface functional groups. In this review, synthetic efforts towards the construction of dendritic fullerene-rich nanostructures have been compiled and will be summarized herein.

  7. Photophysical properties and theoretical calculations of Cu(I) dendrimers

    Energy Technology Data Exchange (ETDEWEB)

    Si, Zhenjun [State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); School of Materials Science and Engineering, Changchun University of Science and Technology, Changchun 130022 (China); An, Chun-Ai [School of Materials Science and Engineering, Changchun University of Science and Technology, Changchun 130022 (China); Song, Shuyan [State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Zhang, Hongjie, E-mail: hongjie@ciac.jl.cn [State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China)

    2014-04-15

    The experimental and theoretical analyses on Cu(I) dendrimers are essential for studying their photophysical properties and facilitating the applications of Cu(I) complexes even though there are relatively few studies in it. Therefore, we synthesize four Cu(I) dendrimers Cu-L1–Cu-L4, the antenna effect is confirmed by the fact that the order of their luminescence quantum yield is Cu-L1

  8. Enzyme-linked DNA dendrimer nanosensors for acetylcholine

    Science.gov (United States)

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

    2015-10-01

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

  9. 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.

  10. 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.

  11. High-Resolution Imaging of Polyethylene Glycol Coated Dendrimers via Combined Atomic Force and Scanning Tunneling Microscopy

    Directory of Open Access Journals (Sweden)

    Shawn Riechers

    2015-01-01

    Full Text Available Dendrimers have shown great promise as drug delivery vehicles in recent years because they can be synthesized with designed size and functionalities for optimal transportation, targeting, and biocompatibility. One of the most well-known termini used for biocompatibility is polyethylene glycol (PEG, whose performance is affected by its actual conformation. However, the conformation of individual PEG bound to soft materials such as dendrimers has not been directly observed. Using atomic force microscopy (AFM and scanning tunneling microscopy (STM, this work characterizes the structure adopted by PEGylated dendrimers with the highest resolution reported to date. AFM imaging enables visualization of the individual dendrimers, as well as the differentiation and characterization of the dendrimer core and PEG shell. STM provides direct imaging of the PEG extensions with high-resolution. Collectively, this investigation provides important insight into the structure of coated dendrimers, which is crucial for the design and development of better drug delivery vehicles.

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

    Science.gov (United States)

    Laumann, Kristoffer; Boas, Ulrik; Larsen, Hjalte M; Heegaard, Peter M H; Bergström, Ann-Louise

    2015-01-12

    Synucleinopathies are neurodegenerative pathologies in which disease progression is closely correlated to brain accumulation of insoluble α-synuclein, a small protein abundantly expressed in neural tissue. Here, two types of modified polypropyleneimine (PPI) dendrimers having either urea or methylthiourea (MTU) surface functional groups were investigated in a cellular model of synucleinopathy. Dendrimers are synthetic macromolecules that may be produced in a range of well-defined molecular sizes. Using cellomics array scan high-content screening, we show that both types of dendrimers are able to significantly reduce intracellular levels of α-synuclein aggregates dependent on the concentration, the type and molecular size of the dendrimer with the bigger size MTU-dendrimers having the highest potency. The intracellular clearance of α-synuclein aggregates by dendrimers was achieved at noncytotoxic concentrations.

  13. Evidence of Oral Translocation of Anionic G6.5 Dendrimers in Mice

    Science.gov (United States)

    Thiagarajan, Giridhar; Sadekar, Shraddha; Greish, Khaled; Ray, Abhijit; Ghandehari, Hamidreza

    2013-01-01

    Development of carrier systems to improve oral bioavailability and target drugs to specific sites continues to be an unmet need. The goal of this study was to evaluate the potential of anionic generation (G) 6.5 poly(amido amine) (PAMAM) dendrimers in oral drug delivery by assessing their in vivo oral translocation. G6.5-COOH dendrimers were characterized for their physiochemical characteristics and acute oral toxicity was assessed in CD-1 mice. The dendrimers were labeled with 125I and their stability evaluated. Oral bioavailability was assessed in the same mouse model. Investigation of the radioactivity profile in plasma, revealed presence of both large and small molecular weight compounds. Detailed area under the curve analysis suggests an effective 9.4% bioavailability of radiolabeled marker associated with G6.5-COOH. Results reported here suggest the potential of dendrimers in permeating gastrointestinal barriers in vivo. PMID:23286733

  14. Unusual concentration-dependent microscopic dynamics of dendrimers in aqueous solution

    Science.gov (United States)

    Wong, Kaikin; Wu, Chin Ming; Lam, Hak Fai; Chathoth, Suresh M.

    2016-05-01

    Dendrimers are novel three-dimensional, hyperbranched globular nanopolymeric macromolecules. The nanoscopic size, narrow polydispersity index, excellent control over molecular structure, availability of multiple functional groups at the periphery, and cavities in the interior made them very attractive candidate for drug delivery. In this communication, we have studied the microscopic dynamics of tetra-acid and pentaerythritol glycidyl ether dendrimers dissolved in aqueous solution with different concentrations. The effects of concentration and temperature to their long-range diffusion process are investigated by dynamic light scattering. Experimental results show a huge variation in the translational diffusion coefficient for the two dendrimers samples. Besides, the dependence of diffusion coefficients on concentration is unusually different in these dendrimer samples. Although the diffusion process follows Arrhenius relation with the temperature in both systems, the activation energy for the diffusion process has a distinct concentration dependence.

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

    Directory of Open Access Journals (Sweden)

    Samreen Khatri

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Redox-modified branched 3D dendrimeric nanostructures are considered a proper tool for the wiring of redox enzymes be-cause they provide both an enzyme-friendly environment and exquisite electron transfer (ET) mediation. ET rates in G3 poly-(amido)amine (PAMAM) dendrimers, covalently attached...... to gold electrodes and labeled with methylene blue (MB), approached 267 s-1 and decreased as the packing density of dendrimers on the electrode surface was increased. A mechanistic analysis of the ET kinetics and fitting to the Marcus relationship showed that as the PAMAM surface coverage was increased......,the ET mechanism switched from surface-confined ET (electron tunneling) in dilute monolayers to diffusional ET (electron hopping) at higher surface populations of dendrimers. Structural changes in the positively charged dendrimers electrostatically compressed at negative charges of the electrode surface...

  17. Cell-penetrable lysine dendrimers for anti-cancer drug delivery: synthesis and preliminary biological evaluation.

    Science.gov (United States)

    Zhao, Jing; Zhou, Rui; Fu, Xiaoyu; Ren, Wen; Ma, Lifang; Li, Ran; Zhao, Yi; Guo, Li

    2014-07-01

    Improving the cell penetration and enhancing the cell selectivity of drugs have been approved for overcoming the major drawbacks of chemotherapeutic agents: the toxicity to normal cells and the drug resistance in tumors. In this paper, lysine dendrimers (G1-G3) were chosen as novel cell-penetrating carriers for anti-cancer drugs based on the internalization mechanism of cell-penetrating peptides and the characteristics of dendritic peptides. After labeling with fluorescein isothiocyanate (FITC), the cell-penetrable capacity of lysine dendrimers was certified by flow cytometric analysis. In a preliminary biological evaluation, the conjugates of lysine dendrimers and 5-fluorouracil showed the expected advantages: stable drug release, low toxicity to normal cells, and moderate inhibition of tumor cells. These results imply that cell-penetrable lysine dendrimers could be potential carriers in drug delivery of anti-cancer medicine. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Modeling the interaction between dendrimers and nucleic acids: a molecular perspective through hierarchical scales.

    Science.gov (United States)

    Pavan, Giovanni M

    2014-12-01

    Cationic dendrimers are promising nanocarriers for gene delivery thanks to their ability to establish strong interactions with oppositely charged strands of DNA and siRNA and to promote their aggregation. The binding between dendrimers and nucleic acids is typically a complex process that involves various types of interactions at different scales. To design efficient dendrimer candidates for DNA and siRNA binding it is necessary to have a detailed understanding of their interactions with oligonucleotides in the solvent. Molecular simulation can support experimental work, providing a privileged point of view on the aggregation process. This Minireview discusses recent computational efforts to unravel dendrimer-oligonucleotide binding, and proposes a perspective of the multiscale aggregation process based on hierarchy and on the transformations of the interacting "molecular units" following intermolecular interactions. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Dendrimers as vectors for genetic material delivery to the nervous system.

    Science.gov (United States)

    Pérez-Martínez, F C; Ocaña, A V; Pérez-Carrión, M D; Ceña, V

    2012-01-01

    Transfection of genetic material into primary neuronal cultures remains a challenge because of the intrinsic difficulty in transfecting this type of cell. This review covers the recent developments in the use of dendrimers for siRNA and DNA transfection in both neuronal and glial cells. Crossing the blood brain barrier crossing represents a challenge for the effective use of dendrimer-mediated delivery of therapeutic agents to the central nervous system. We will discuss the effectiveness, both in vitro and in vivo, of various dendrimers in delivering genetic material to neural tissue and its ability to cross the blood-brain barrier. In addition, the use of dendrimers as a potential new therapy in the treatment of glioblastoma will be presented.

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

    DEFF Research Database (Denmark)

    Ficker, Mario

    the formation of singlet oxygen and enabled photodynamic therapy. In vivo studies in mice and rabbit models showed that the dendrimer phthalocyanine formulations could target the macrophage-rich plaque areas, which are the most vulnerable and dangerous plaques. No localization of the compound in the healthy...... therapy. For this purpose, a dendrimer nanoparticle system was developed that showed promising cytotoxicity and immunogenicity. These dendrimers were capable of solvating lipophilic phthalocyanines, which are second-generation photosensitizers. The dendrimer phthalocyanine conjugates had light emission...... endothelium was found, which is a necessity in order to successfully treat a patient without injuring healthy tissue. The high uorescence intensity and the selective targeting of the plaques enabled in vivo 2D-NIRF imaging using an angioplasty rabbit model. Photodynamic therapy studies were successfully...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-01-15

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-10-01

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

  3. Dendrimers of citric acid and poly (ethylene glycol) as the new drug-delivery agents.

    Science.gov (United States)

    Namazi, H; Adeli, M

    2005-04-01

    Citric acid-polyethylene glycol-citric acid (CPEGC) triblock dendrimers as biocompatible compounds containing G(1), G(2) and G(3) were applied as the drug-delivery systems. Some of the small size molecules and drugs are trapped with the above-synthesized dendrimers. The guest molecules, which are hydrophobic when trapped into the suitable sites of dendrimers, are becoming soluble in aqueous solution. The quantity of trapped molecules and drugs such as 5-amino salicylic acid (5-ASA), pyridine, mefenamic acid, and diclofenac was measured. The drug/dendrimer complexes remained in room temperature for about 10 months and after this long time they were stable and the drugs were not released. Also, the controlled release of the above-mentioned molecules and drugs in vitro conditions was investigated. The structure definition and controlled release of the molecules and drugs were carried out using different spectroscopy methods.

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    generation were synthesized and investigated as potential materials for high capacity optical data storage with their dimerization efficiency compared to uracil as a reference compound. This allows the impact of increasing the generation number of the dendrimers, both the number of chromophores, as well...... as the different steric environments, on the performance of each series of dendrimers to be investigated. The (uracil)(12)-[G-2]-bis-MPA and (uracil)(8)-[G-1]-PAMAM were observed to have high dimerization efficiency in solution with different behavior being observed for the PAMAM and bis-MPA dendrimers....... The dendrimers with the best dimerization efficiency in solution were then examined in the solid state as thin films cast on quartz plates, and their film qualities along with their photodimerization performance studied. High quality films with a transmission response of up to 70% in 55 s. when irradiated at 257...

  5. Radionuclide 131I-labeled multifunctional dendrimers for targeted SPECT imaging and radiotherapy of tumors

    Science.gov (United States)

    Zhu, Jingyi; Zhao, Lingzhou; Cheng, Yongjun; Xiong, Zhijuan; Tang, Yueqin; Shen, Mingwu; Zhao, Jinhua; Shi, Xiangyang

    2015-10-01

    We report the synthesis, characterization, and utilization of radioactive 131I-labeled multifunctional dendrimers for targeted single-photon emission computed tomography (SPECT) imaging and radiotherapy of tumors. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 (G5.NH2) were sequentially modified with 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO) and folic acid (FA) linked with polyethylene glycol (PEG), followed by acetylation modification of the dendrimer remaining surface amines and labeling of radioactive iodine-131 (131I). The generated multifunctional 131I-G5.NHAc-HPAO-PEG-FA dendrimers were characterized via different methods. We show that prior to 131I labeling, the G5.NHAc-HPAO-PEG-FA dendrimers conjugated with approximately 9.4 HPAO moieties per dendrimer are noncytotoxic at a concentration up to 20 μM and are able to target cancer cells overexpressing FA receptors (FAR), thanks to the modified FA ligands. In the presence of a phenol group, radioactive 131I is able to be efficiently labeled onto the dendrimer platform with good stability and high radiochemical purity, and render the platform with an ability for targeted SPECT imaging and radiotherapy of an FAR-overexpressing xenografted tumor model in vivo. The designed strategy to use the facile dendrimer nanotechnology may be extended to develop various radioactive theranostic nanoplatforms for targeted SPECT imaging and radiotherapy of different types of cancer.We report the synthesis, characterization, and utilization of radioactive 131I-labeled multifunctional dendrimers for targeted single-photon emission computed tomography (SPECT) imaging and radiotherapy of tumors. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 (G5.NH2) were sequentially modified with 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO) and folic acid (FA) linked with polyethylene glycol (PEG), followed by acetylation modification of the dendrimer remaining surface amines and

  6. 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.

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

    Science.gov (United States)

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

    2015-11-09

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

  8. Probing Photophysical Processes in Individual Multichromophoric Dendrimers by Single-Molecule Spectroscopy

    NARCIS (Netherlands)

    Hofkens, Johan; Maus, Michael; Gensch, Thomas; Vosch, Tom; Cotlet, Mircea; Köhn, Fabian; Herrmann, Andreas; Müllen, Klaus; Schryver, Frans De

    2000-01-01

    Individual multichromophoric dendrimer molecules, bearing eight perylenecarboximide chromophores at the rim, immobilized in a thin polyvinylbutyral (PVB) film were studied by far-field fluorescence microscopy. Fluorescence intensity trajectories as a function of time (transients), spectra, and decay

  9. "Click" dendrimers: synthesis, redox sensing of Pd(OAc)2, and remarkable catalytic hydrogenation activity of precise Pd nanoparticles stabilized by 1,2,3-triazole-containing dendrimers.

    Science.gov (United States)

    Ornelas, Cátia; Aranzaes, Jaime Ruiz; Salmon, Lionel; Astruc, Didier

    2008-01-01

    "Click" dendrimers containing 1,2,3-triazolyl ligands that coordinate to PdII(OAc)2 have been synthesized in view of catalytic applications. Five of these dendrimers contain ferrocenyl termini directly attached to the triazole ligand in order to monitor the number of PdII that are introduced into the dendrimers by cyclic voltammetry. Reduction of the PdII-triazole dendrimers by using NaBH4 or methanol yields Pd nanoparticles (PdNPs) that are stabilized either by several dendrimers (G0, DSN) or by encapsulation inside a dendrimer (G1 and G2: DEN), as confirmed by TEM. Relative to PAMAM-DENs (PAMAM=poly(amidoamine)), the "click" DSNs and DENs show a remarkable efficiency and stability for olefin hydrogenation under ambient conditions of various substrates. The influence of the reductant of PdII bound to the dendrimers is dramatic, reduction with methanol leading to much higher catalytic activity than reduction with NaBH4. The most active NPs are shown to be those derived from dendrimer G1, and variation of its termini groups (ferrocenyl, alkyl, phenyl) allowed us to clearly delineate, optimize, and rationalize the role of the dendrimer frameworks on the catalytic efficiencies. Finally, hydrogenation of various substrates catalyzed by these PdNPs shows remarkable selectivity features.

  10. Interaction study between maltose-modified PPI dendrimers and lipidic model membranes.

    Science.gov (United States)

    Wrobel, Dominika; Appelhans, Dietmar; Signorelli, Marco; Wiesner, Brigitte; Fessas, Dimitrios; Scheler, Ulrich; Voit, Brigitte; Maly, Jan

    2015-07-01

    The influence of maltose-modified poly(propylene imine) (PPI) dendrimers on dimyristoylphosphatidylcholine (DMPC) or dimyristoylphosphatidylcholine/dimyristoylphosphatidylglycerol (DMPC/DMPG) (3%) liposomes was studied. Fourth generation (G4) PPI dendrimers with primary amino surface groups were partially (open shell glycodendrimers - OS) or completely (dense shell glycodendrimers - DS) modified with maltose residues. As a model membrane, two types of 100nm diameter liposomes were used to observe differences in the interactions between neutral DMPC and negatively charged DMPC/DMPG bilayers. Interactions were studied using fluorescence spectroscopy to evaluate the membrane fluidity of both the hydrophobic and hydrophilic parts of the lipid bilayer and using differential scanning calorimetry to investigate thermodynamic parameter changes. Pulsed-filed gradient NMR experiments were carried out to evaluate common diffusion coefficient of DMPG and DS PPI in D2O when using below critical micelle concentration of DMPG. Both OS and DS PPI G4 dendrimers show interactions with liposomes. Neutral DS dendrimers exhibit stronger changes in membrane fluidity compared to OS dendrimers. The bilayer structure seems more rigid in the case of anionic DMPC/DMPG liposomes in comparison to pure and neutral DMPC liposomes. Generally, interactions of dendrimers with anionic DMPC/DMPG and neutral DMPC liposomes were at the same level. Higher concentrations of positively charged OS dendrimers induced the aggregation process with negatively charged liposomes. For all types of experiments, the presence of NaCl decreased the strength of the interactions between glycodendrimers and liposomes. Based on NMR diffusion experiments we suggest that apart from electrostatic interactions for OS PPI hydrogen bonds play a major role in maltose-modified PPI dendrimer interactions with anionic and neutral model membranes where a contact surface is needed for undergoing multiple H-bond interactions between

  11. Dendrimers Target the Ischemic Lesion in Rodent and Primate Models of Nonarteritic Anterior Ischemic Optic Neuropathy.

    Science.gov (United States)

    Guo, Yan; Johnson, Mary A; Mehrabian, Zara; Mishra, Manoj K; Kannan, Rangaramanujam; Miller, Neil R; Bernstein, Steven L

    2016-01-01

    Polyamidoamine dendrimer nanoparticles (~ 4 nanometers) are inert polymers that can be linked to biologically active compounds. These dendrimers selectively target and accumulate in inflammatory cells upon systemic administration. Dendrimer-linked compounds enable sustained release of therapeutic compounds directly at the site of damage. The purpose of this study was to determine if dendrimers can be used to target the optic nerve (ON) ischemic lesion in our rodent and nonhuman primate models of nonarteritic anterior ischemic optic neuropathy (NAION), a disease affecting >10,000 individuals in the US annually, and for which there currently is no effective treatment. NAION was induced in male Long-Evans rats (rNAION) and in one adult male rhesus monkey (pNAION) using previously described procedures. Dendrimers were covalently linked to near-infrared cyanine-5 fluorescent dye (D-Cy5) and injected both intravitreally and systemically (in the rats) or just systemically (in the monkey) to evaluate D-Cy5 tissue accumulation in the eye and optic nerve following induction of NAION. Following NAION induction, Cy-5 dendrimers selectively accumulated in astrocytes and circulating macrophages. Systemic dendrimer administration provided the best penetration of the ON lesion site when injected shortly after induction. Systemic administration 1 day post-induction in the pNAION model gave localization similar to that seen in the rats. Dendrimers selectively target the ischemic ON lesion after induction of both rNAION and pNAION. Systemic nanoparticle-linked therapeutics thus may provide a powerful, targeted and safe approach to NAION treatment by providing sustained and focused treatment of the cells directly affected by ischemia.

  12. Effects of Polyamidoamine Dendrimers on a 3-D Neurosphere System Using Human Neural Progenitor Cells.

    Science.gov (United States)

    Zeng, Yang; Kurokawa, Yoshika; Zeng, Qin; Win-Shwe, Tin-Tin; Nansai, Hiroko; Zhang, Zhenya; Sone, Hideko

    2016-07-01

    The practical application of engineered nanomaterials or nanoparticles like polyamidoamine (PAMAM) dendrimers has been promoted in medical devices or industrial uses. The safety of PAMAM dendrimers needs to be assessed when used as a drug carrier to treat brain disease. However, the effects of PAMAM on the human nervous system remain unknown. In this study, human neural progenitor cells cultured as a 3D neurosphere model were used to study the effects of PAMAM dendrimers on the nervous system. Neurospheres were exposed to different G4-PAMAM dendrimers for 72 h at concentrations of 0.3, 1, 3, and 10 μg/ml. The biodistribution was investigated using fluorescence-labeled PAMAM dendrimers, and gene expression was evaluated using microarray analysis followed by pathway and network analysis. Results showed that PAMAM dendrimer nanoparticles can penetrate into neurospheres via superficial cells on them. PAMAM-NH2 but not PAMAM-SC can inhibit neurosphere growth. A reduced number of MAP2-positive cells in flare regions were inhibited after 10 days of differentiation, indicating an inhibitory effect of PAMAM-NH2 on cell proliferation and neuronal migration. A microarray assay showed 32 dendrimer toxicity-related genes, with network analysis showing 3 independent networks of the selected gene targets. Inducible immediate early gene early growth response gene 1 (Egr1), insulin-like growth factor-binding protein 3 (IGFBP3), tissue factor pathway inhibitor (TFPI2), and adrenomedullin (ADM) were the key genes in each network, and the expression of these genes was significantly down regulated. These findings suggest that exposure of neurospheres to PAMAM-NH2 dendrimers affects cell proliferation and migration through pathways regulated by Egr1, IGFBP3, TFPI2, and ADM. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. 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.

  14. Development of a Topical Resveratrol Formulation for Commercial Applications Using Dendrimer Nanotechnology

    OpenAIRE

    Tyler Pentek; Eric Newenhouse; Brennin O’Brien; Abhay Singh Chauhan

    2017-01-01

    Resveratrol (RSV) is well known for its anti-oxidant and anti-aging properties. However, resveratrol is insoluble in water and has stability issues. Recently, efforts were placed to prepare a resveratrol-based advanced anti-aging topical product but it contains harsh organic solvents and oils that could be harmful to the human body and the environment. Hence, we propose the use of a multifunctional dendrimer to solve the solubility and stability issues of resveratrol. A dendrimer-resveratrol ...

  15. A highly effective polymerase chain reaction enhancer based on dendrimer-entrapped gold nanoparticles.

    Science.gov (United States)

    Chen, Jingjing; Cao, Xueyan; Guo, Rui; Shen, Mingwu; Peng, Chen; Xiao, Tongyu; Shi, Xiangyang

    2012-01-07

    In molecular biology, polymerase chain reaction (PCR) has played an important role but suffers a general problem of low efficiency and specificity. Development of suitable PCR additives to improve the specificity and efficiency still remains a great challenge. Here we report the use of dendrimer-entrapped gold nanoparticles (Au DENPs) as a novel class of enhancers to improve the specificity and efficiency of PCR. We show that the Au DENPs prepared using amine-terminated generation 5 poly(amidoamine) dendrimers (G5.NH(2)) as templates are much more effective than the same dendrimers without AuNPs entrapped in improving the specificity and efficiency of an error-prone two-round PCR system. With the increase of the molar ratio between Au atom and G5.NH(2) dendrimer in the Au DENPs, the optimum concentration of Au DENPs used to improve the PCR specificity and efficiency is decreased and can be as low as 0.37 nM when the Au atom/G5.NH(2) dendrimer molar ratio reaches 100:1. Our PCR results along with the dynamic light scattering data suggest that unlike the flexible soft dendrimers without NPs entrapped that may display a non-spherical shape when interacting with the PCR components, the Au DENPs with increasing Au atom/dendrimer molar ratio are able to reserve the spherical shape of dendrimers, enabling much more efficient interaction with the PCR components. Therefore, as a NP-based PCR enhancer, both the surface charge and the shape of the particles should be responsible for effective interaction with the PCR components for improving the PCR specificity and efficiency. Furthermore, the used Au DENPs were proved to be stable after the PCR process, enabling them to be potentially used for enhancing different PCR systems. This journal is © The Royal Society of Chemistry 2012

  16. Liquid Crystals of Dendron-Like Pt Complexes Processable Into Nanofilms Dendrimers. Phase 2. Cholesteric Liquid Crystal Glass Platinum Acetylides

    Science.gov (United States)

    2014-08-01

    Std. Z39.18 Final Report Liquid Crystals of Dendron-Like Pt Complexes Processable Into Nanofilms. Dendrimers Eduardo Arias...to pack and also the presence of a polar group. Figure 4. Summary of phase behavior. DENDRIMERS New Denrimers. The synthesis...purification and some spectral characteristics of the new dendrimers shown in Fig 5 were reported in AFOSR FA9550-11-1-0169, May, 2013. Further

  17. 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

    2018-01-07

    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.

  18. Investigation of Melts of Polybutylcarbosilane Dendrimers by 1H NMR Spectroscopy.

    Science.gov (United States)

    Matveev, Vladimir V; Markelov, Denis A; Dvinskikh, Sergey V; Shishkin, Andrei N; Tyutyukin, Konstantin V; Penkova, Anastasia V; Tatarinova, Elena A; Ignat'eva, Galina M; Milenin, Sergey A

    2017-10-20

    Melts of polybutylcarbosilane (PBC) dendrimers from third (G3) up to sixth (G6) generations are investigated by 1H NMR spectroscopy in a wide temperature range up to 493 K. At room temperature, NMR spectra of G3-G5 dendrimers exhibit resolved, solution-like spectra ("liquid" phase). In contrast, the spectrum of the G6 dendrimer is characterized by a single unresolved broad line at whole temperature range, which supports the presence of an anomalous phase state of G6 at temperatures higher than glass transition temperature. For the first time, an unexpected transition of G5 dendrimer from a molecular liquid state to an anomalous state/phase upon temperature increase has been detected using NMR data. Specifically, an additional wide background line appears in the G5 spectrum above 473 K, and this line corresponds to a G5 state characterized by restricted molecular mobility, i.e., a state similar to the "anomalous" phase of G6 melt. The fraction of the G5 dendrimers in "anomalous" phase at 493 K is approximately 40%. Analysis of the spectral shapes suggests that changes in the G5 dendrimers are reversible with temperature.

  19. Nanomedicine for prion disease treatment: new insights into the role of dendrimers.

    Science.gov (United States)

    McCarthy, James M; Appelhans, Dietmar; Tatzelt, Jörg; Rogers, Mark S

    2013-01-01

    Despite their devastating impact, no effective therapeutic yet exists for prion diseases at the symptomatic stage in humans or animals. Progress is hampered by the difficulty in identifying compounds that affect PrP (Sc) and the necessity of any potential therapeutic to gain access to the CNS. Synthetic polymers known as dendrimers are a particularly promising candidate in this area. Studies with cell culture models of prion disease and prion infected brain homogenate have demonstrated that numerous species of dendrimers eliminate PrP (Sc) in a dose and time dependent fashion and specific glycodendrimers are capable of crossing the CNS. However, despite their potential a number of important questions remained unanswered such as what makes an effective dendrimer and how dendrimers eliminate prions intracellularly. In a number of recent studies we have tackled these questions and revealed for the first time that a specific dendrimer can inhibit the intracellular conversion of PrP (C) to PrP (Sc) and that a high density of surface reactive groups is a necessity for dendrimers in vitro anti-prion activity. Understanding how a therapeutic works is a vital component in maximising its activity and these studies therefore represent a significant development in the race to find effective treatments for prion diseases.

  20. Molecular Determinants of the Cellular Entry of Asymmetric Peptide Dendrimers and Role of Caveolae.

    Directory of Open Access Journals (Sweden)

    Prarthana V Rewatkar

    Full Text Available Caveolae are flask-shaped plasma membrane subdomains abundant in most cell types that participate in endocytosis. Caveola formation and functions require membrane proteins of the caveolin family, and cytoplasmic proteins of the cavin family. Cationic peptide dendrimers are non-vesicular chemical carriers that can transport pharmacological agents or genetic material across the plasma membrane. We prepared a panel of cationic dendrimers and investigated whether they require caveolae to enter into cells. Cell-based studies were performed using wild type or caveola-deficient i.e. caveolin-1 or PTRF gene-disrupted cells. There was a statistically significant difference in entry of cationic dendrimers between wild type and caveola-deficient cells. We further unveiled differences between dendrimers with varying charge density and head groups. Our results show, using a molecular approach, that (i expression of caveola-forming proteins promotes cellular entry of cationic dendrimers and (ii dendrimer structure can be modified to promote endocytosis in caveola-forming cells.

  1. Molecular Determinants of the Cellular Entry of Asymmetric Peptide Dendrimers and Role of Caveolae.

    Science.gov (United States)

    Rewatkar, Prarthana V; Parekh, Harendra S; Parat, Marie-Odile

    2016-01-01

    Caveolae are flask-shaped plasma membrane subdomains abundant in most cell types that participate in endocytosis. Caveola formation and functions require membrane proteins of the caveolin family, and cytoplasmic proteins of the cavin family. Cationic peptide dendrimers are non-vesicular chemical carriers that can transport pharmacological agents or genetic material across the plasma membrane. We prepared a panel of cationic dendrimers and investigated whether they require caveolae to enter into cells. Cell-based studies were performed using wild type or caveola-deficient i.e. caveolin-1 or PTRF gene-disrupted cells. There was a statistically significant difference in entry of cationic dendrimers between wild type and caveola-deficient cells. We further unveiled differences between dendrimers with varying charge density and head groups. Our results show, using a molecular approach, that (i) expression of caveola-forming proteins promotes cellular entry of cationic dendrimers and (ii) dendrimer structure can be modified to promote endocytosis in caveola-forming cells.

  2. COMPUTER SIMULATION OF LOCAL MOBILITY IN DENDRIMERS WITH ASYMMETRIC BRANCHING BY BROWNIAN DYNAMICS METHOD

    Directory of Open Access Journals (Sweden)

    O. V. Shavykin

    2016-09-01

    Full Text Available The Brownian dynamics method has been used to study the effect of the branching asymmetry on the local orientational mobility of segments and bonds in dendrimers in good solvent. “Coarse-grained” models of flexible dendrimers with different branching symmetry but with the same average segment length were considered. The frequency dependences of the rate of the spin-lattice relaxation nuclear magnetic resonance (NMR [1/T1H(H] for segments or bonds located at different distances from terminal monomers were calculated. After the exclusion of the contribution of the overall dendrimer rotation the position of the maxima of the frequency dependences [1/T1H(ωH] for different segments with the same length doesn’t depend on their location inside a dendrimer both for phantom models and for models with excluded volume interactions. This effect doesn’t depend also on the branching symmetry, but the position of the maximum [1/T1H(ωH] is determined by the segment length. For bonds inside segments the positions of the maximum [1/T1H(ωH] coincide for all models considered. Therefore, the obtained earlier conclusion about the weak influence of the excluded volume interactions on the local dynamics in the flexible symmetric dendrimers can be generalized for dendrimers with an asymmetric branching.

  3. In vitro PAMAM, phosphorus and viologen-phosphorus dendrimers prevent rotenone-induced cell damage.

    Science.gov (United States)

    Milowska, Katarzyna; Szwed, Aleksandra; Zablocka, Maria; Caminade, Anne-Marie; Majoral, Jean-Pierre; Mignani, Serge; Gabryelak, Teresa; Bryszewska, Maria

    2014-10-20

    We have investigated whether polyamidoamine (PAMAM), phosphorus (pd) and viologen-phosphorus (vpd) dendrimers can prevent damage to embryonic mouse hippocampal cells (mHippoE-18) caused by rotenone, which is used as a pesticide, insecticide, and as a nonselective piscicide, that works by interfering with the electron transport chain in mitochondria. Several basic aspects, such as cell viability, production of reactive oxygen species and changes in mitochondrial transmembrane potential, were analyzed. mHippoE-18 cells were treated with these structurally different dendrimers at 0.1μM. A 1h incubation with dendrimers was followed by the addition of rotenone at 1μM, and a further 24h incubation. PAMAM, phosphorus and viologen-phosphorus dendrimers all increased cell viability (reduced cell death-data need to be compared with untreated controls). A lower level of reactive oxygen species and a favorable effect on mitochondrial system were found with PAMAM and viologen-phosphorus dendrimers. These results indicate reduced toxicity in the presence of dendrimers. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Sanaz Motamedi

    2011-06-01

    Full Text Available Introduction: Citric acid-polyethylene glycol-citric acid (CPEGC triblock dendrimers can serve as potential delivery systems. Methods: In this investigation, CPEGC triblock dendrimers were synthesized and then imidazole groups were conjugated onto the surface of the G1, G2 and G3 of the obtained dendrimers. In order to study the type of the interactions between the functionalized dendrimers and a drug molecule, Naproxen which contains acidic groups, was examined as a hydrophobic drug in which the interactions would be of the electrostatic kind between its acidic groups and the lone pair electrons of nitrogen atom in imidazole groups. The quantity of the trapped drug and also the amount of its release were measured with UV spectrometric method in pH 1, 7.4 and 10. The average diameter of the nanocarriers was measured by Dynamic Light Scattering (DLS technique Results: The size range of particles was determined to be 16-50 nm for different generations. The rate of the release increased in pH=10 in all generations due to the increase in Naproxen solubility and the hydrolysis of the esteric bonds in the mentioned pH. The results showed that the amount of the trapped drug increased with the increase in the generation of the dendrimer and pH. Conclusion: Based on our findings, we suggest CPEGC triblock dendrimers possess great potential to be used as drug/gene delivery system.

  5. Interactions of PAMAM dendrimers with SDS at the solid-liquid interface.

    Science.gov (United States)

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

    2013-05-14

    This work addresses structural and nonequilibrium effects of the interactions between well-defined cationic poly(amidoamine) PAMAM dendrimers of generations 4 and 8 and the anionic surfactant sodium dodecyl sulfate (SDS) at the hydrophilic silica-water interface. Neutron reflectometry and quartz crystal microbalance with dissipation monitoring were used to reveal the adsorption from premixed dendrimer/surfactant solutions as well as sequential addition of the surfactant to preadsorbed layers of dendrimers. PAMAM dendrimers of both generations adsorb to hydrophilic silica as a compact monolayer, and the adsorption is irreversible upon rinsing with salt solution. SDS adsorbs on the dendrimer layer and at low bulk concentrations causes the expansion of the dendrimer layers on the surface. When the bulk concentration of SDS is increased, the surfactant layer consists of aggregates or bilayer-like structures. The adsorption of surfactant is reversible upon rinsing, but slight changes of the structure of the preadsorbed PAMAM monolayer were observed. The adsorption from premixed solutions close to charge neutrality results in thick multilayers, but the surface excess is lower when the bulk complexes have a net negative charge. A critical examination of the pathway of adsorption for the interactions of SDS with preadsorbed PAMAM monolayers and premixed PAMAM/SDS solutions with hydrophilic silica revealed that nonequilibrium effects are important only in the latter case, and the application of a thermodynamic model to such experimental data would be inappropriate.

  6. 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.

  7. 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

  8. Cross olefin metathesis for the selective functionalization, ferrocenylation, and solubilization in water of olefin-terminated dendrimers, polymers, and gold nanoparticles and for a divergent dendrimer construction.

    Science.gov (United States)

    Ornelas, Cátia; Méry, Denise; Cloutet, Eric; Ruiz Aranzaes, Jaime; Astruc, Didier

    2008-01-30

    Olefin cross metathesis was used to efficiently functionalize polyolefin dendrimers, polymers, and gold nanoparticles using the second-generation Grubbs catalyst. In these structures, the tethers were lengthened to prevent the facile cross metathesis that otherwise predominates in polyolefin dendrimers having short tethers. This synthetic strategy allows the one-step access to polyacid, polyester, and polyferrocenyl structures from polyolefins. Cross metathesis is also used to efficiently achieve an iterative divergent dendritic construction. All the cross metathesis reactions were monitored by 1H NMR showing the chemo-, regio-, and stereoselectivity. MALDI-TOF mass spectrometry was a very useful technique to confirm the efficiency of this synthetic strategy.

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

    Science.gov (United States)

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

    2017-02-01

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

  10. 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

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

    Directory of Open Access Journals (Sweden)

    J.M. Ilnytskyi

    2010-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-10-15

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

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

    Science.gov (United States)

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

    2013-02-01

    Targeted delivery of imaging agents to cells can be optimized with the understanding of uptake and efflux rates. Cellular uptake of macromolecules is studied frequently with fluorescent probes. We hypothesized that the internalization and efflux of fluorescently labeled macromolecules into and out of mammalian cells could be quantified by confocal microscopy to determine the rate of uptake and efflux, from which the mass transfer coefficient is calculated. The cellular influx and efflux of a third generation poly(amido amine) (PAMAM) dendrimer labeled with an Alexa Fluor 555 dye was measured in Capan-1 pancreatic cancer cells using confocal fluorescence microscopy. The Capan-1 cells were also labeled with 5-chloromethylfluorescein diacetate (CMFDA) green cell tracker dye to delineate cellular boundaries. A dilution curve of the fluorescently labeled PAMAM dendrimer enabled quantification of the concentration of dendrimer in the cell. A simple mass transfer model described the uptake and efflux behavior of the PAMAM dendrimer. The effective mass transfer coefficient was found to be 0.054±0.043μm/min, which corresponds to a rate constant of 0.035±0.023min(-1) for uptake of the PAMAM dendrimer into the Capan-1 cells. The effective mass transfer coefficient was shown to predict the efflux behavior of the PAMAM dendrimer from the cell if the fraction of labeled dendrimer undergoing non-specific binding is accounted for. This work introduces a novel method to quantify the mass transfer behavior of fluorescently labeled macromolecules into mammalian cells. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Effects of PAMAM dendrimers in the mouse brain after a single intranasal instillation.

    Science.gov (United States)

    Win-Shwe, Tin-Tin; Sone, Hideko; Kurokawa, Yoshika; Zeng, Yang; Zeng, Qin; Nitta, Hiroshi; Hirano, Seishiro

    2014-08-04

    Dendrimers are highly branched spherical nanomaterials produced for use in diagnostic and therapeutic applications such as a drug delivery system. The toxicological profiles of dendrimers are largely unknown. We investigated the in vivo effects of nasal exposure to polyamidoamine (PAMAM) dendrimers on their effects on neurological biomarkers in the mouse brain. A single dose of PAMAM dendrimers (3 or 15μg/mouse) was intranasally administered to 8-week old male BALB/c mice. Twenty-four hours after administration, the olfactory bulb, hippocampus, and cerebral cortex were collected and potential biomarkers in the blood and brain were examined using blood marker, microarray and real-time RT-PCR analyses. No remarkable changes in standard serum biochemical markers were observed in the blood. A microarray analysis showed the alterations of the genes expression level related to pluripotent network, serotonin-anxiety pathway, TGF-beta receptor signaling, prostaglandin synthesis-regulation, complement-coagulation cascades, and chemokine-signaling pathway and non-odorant GPCR signaling pathways in brain tissues. Brain derived-neurotrophic factor mRNA was up-regulated in the hippocampus and cerebral cortex in mice treated with a high dose of dendrimers. These findings suggest that PAMAM dendrimers may reach the brain via the systemic circulation or an olfactory nerve route after intranasal instillation, and indicate that a single intranasal administration of PAMAM dendrimers may potentially lead to neuronal effects by modulating the gene expression of brain-derived neurotrophic factor signaling pathway. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2017-05-26

    A multivalent phosphorus dendrimer 1G3 and its corresponding Cu-complex, 1G3-Cu have been recently identified as agents retaining high antiproliferative potency. This antiproliferative capacity was preserved in cell lines overexpressing the efflux pump ABC B1, whereas cross-resistance was observed in ovarian cancer cell lines resistant to cisplatin. Theoretical 3D models were constructed: the dendrimers appear as irregularly shaped disk-like nano-objects of about 22 Å thickness and 49 Å diameter, which accumulated in cells after penetration by endocytosis. To get insight in their mode of action, cell death pathways have been examined in human cancer cell lines: early apoptosis was followed by secondary necrosis after multivalent phosphorus dendrimers exposure. The multivalent plain phosphorus dendrimer 1G3 moderately activated caspase-3 activity, in contrast with the multivalent Cu-conjugated phosphorus dendrimer 1G3-Cu which strikingly reduced the caspase-3 content and activity. This decrease of caspase activity is not related to the presence of copper, since inorganic copper has no or little effect on caspase-3. Conversely the potent apoptosis activation could be related to a noticeable translocation of Bax to the mitochondria, resulting in the release of AIF into the cytosol, its translocation to the nucleus and a severe DNA fragmentation, without alteration of the cell cycle. The multivalent Cu-conjugated phosphorus dendrimer is more efficient than its non-complexed analog to activate this pathway in close relationship with the higher antiproliferative potency. Therefore, this multivalent Cu-conjugated phosphorus dendrimer 1G3-Cu can be considered as a new and promising first-in-class antiproliferative agent with a distinctive mode of action, inducing apoptosis tumor cell death through Bax activation pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. Nitric Oxide-Releasing Amphiphilic Poly(amidoamine) (PAMAM) Dendrimers as Antibacterial Agents

    Science.gov (United States)

    Lu, Yuan; Slomberg, Danielle L.; Shah, Anand; Schoenfisch, Mark H.

    2013-01-01

    A series of amphiphilic nitric oxide (NO)-releasing poly(amidoamine) (PAMAM) dendrimers with different exterior functionalities were synthesized by a ring-opening reaction between primary amines on the dendrimer and propylene oxide (PO), 1,2-epoxy-9-decene (ED), or a ratio of the two, followed by reaction with NO at 10 atm to produce N-diazeniumdiolate-modified scaffolds with a total storage of ~1 μmol/mg. The hydrophobicity of the exterior functionality was tuned by varying the ratio of PO and ED grafted onto the dendrimers. The bactericidal efficacy of these NO-releasing vehicles against established Gram-negative Pseudomonas aeruginosa biofilms was then evaluated as a function of dendrimer exterior hydrophobicity (i.e., ratio of PO/ED), size (i.e., generation), and NO release. Both the size and exterior functionalization of dendrimer proved important to a number of parameters including dendrimer-bacteria association, NO delivery efficiency, bacteria membrane disruption, migration within the biofilm, and toxicity to mammalian cells. Although enhanced bactericidal efficacy was observed for the hydrophobic chains (e.g., ED), toxicity to L929 mouse fibroblast cells was also noted at concentrations necessary to reduce bacterial viability by 5-logs (99.999% killing). The optimal PO to ED ratios for biofilm eradication with minimal toxicity against L929 mouse fibroblast cells were 7:3 and 5:5. The study presented herein demonstrated the importance of both dendrimer size and exterior properties in determining efficacy against established biofilms without compromising biocompatibility to mammalian cells. PMID:23962307

  17. Comparative biodistribution of PAMAM dendrimers and HPMA copolymers in ovarian-tumor-bearing mice.

    Science.gov (United States)

    Sadekar, S; Ray, A; Janàt-Amsbury, M; Peterson, C M; Ghandehari, H

    2011-01-10

    The biodistribution profile of a series of linear N-(2-hydroxylpropyl)methacrylamide (HPMA) copolymers was compared with that of branched poly(amido amine) dendrimers containing surface hydroxyl groups (PAMAM-OH) in orthotopic ovarian-tumor-bearing mice. Below an average molecular weight (MW) of 29 kDa, the HPMA copolymers were smaller than the PAMAM-OH dendrimers of comparable molecular weight. In addition to molecular weight, hydrodynamic size and polymer architecture affected the biodistribution of these constructs. Biodistribution studies were performed by dosing mice with (125)iodine-labeled polymers and collecting all major organ systems, carcass, and excreta at defined time points. Radiolabeled polymers were detected in organ systems by measuring gamma emission of the (125)iodine radiolabel. The hyperbranched PAMAM dendrimer, hydroxyl-terminated, generation 5 (G5.0-OH), was retained in the kidney over 1 week, whereas the linear HPMA copolymer of comparable molecular weight was excreted into the urine and did not show persistent renal accumulation. PAMAM dendrimer, hydroxyl-terminated, generation 6.0 (G6.0-OH), was taken up by the liver to a higher extent, whereas the HPMA copolymer of comparable molecular weight was observed to have a plasma exposure three times that of this dendrimer. Tumor accumulation and plasma exposure were correlated with the hydrodynamic sizes of the polymers. PAMAM dendrimer, hydroxyl-terminated, generation 7.0 (G7.0-OH), showed extended plasma circulation, enhanced tumor accumulation, and prolonged retention with the highest tumor/blood ratio for the polymers under study. Head-to-head comparative study of HPMA copolymers and PAMAM dendrimers can guide the rational design and development of carriers based on these systems for the delivery of bioactive and imaging agents.

  18. COMPARATIVE BIODISTRIBUTION OF PAMAM DENDRIMERS AND HPMA COPOLYMERS IN OVARIAN TUMOR-BEARING MICE

    Science.gov (United States)

    Sadekar, S.; Ray, A.; Janàt-Amsbury, M.; Peterson, C. M.; Ghandehari, H.

    2010-01-01

    The biodistribution profile of a series of linear N-(2-hydroxylpropyl)methacrylamide (HPMA) copolymers were compared with that of branched poly (amido amine) dendrimers containing surface hydroxyl groups (PAMAM-OH) in orthotopic ovarian tumor-bearing mice. Below an average molecular weight (MW) of 29 kDa, the HPMA copolymers were smaller than the PAMAM-OH dendrimers of comparable molecular weight. In addition to molecular weight, hydrodynamic size and polymer architecture affected the biodistribution of these constructs. Biodistribution studies were performed by dosing mice with 125Iodine-labeled polymers and collecting all major organ systems, carcass and excreta at defined time points. Radiolabeled polymers were detected in organ systems by measuring gamma emission of the 125Iodine radiolabel. The hyperbranched PAMAM dendrimer, hydroxyl terminated, generation 5 (G5.0-OH) was retained in the kidney over one week while the linear HPMA copolymer of comparable molecular weight was excreted into the urine and did not show persistent renal accumulation. PAMAM dendrimer, hydroxyl terminated, generation 6.0 (G6.0-OH) was taken up by the liver to a higher extent while the HPMA copolymer of comparable molecular weight was observed to have a plasma exposure three times that of this dendrimer. Tumor accumulation and plasma exposure were correlated with the hydrodynamic sizes of the polymers. PAMAM dendrimer, hydroxyl terminated, generation 7.0 (G7.0-OH) showed extended plasma circulation, enhanced tumor accumulation and prolonged retention with the highest tumor/blood ratio for the polymers under study. Head-to-head comparative study of HPMA copolymers and PAMAM dendrimers can guide the rational design and development of carriers based on these systems for delivery of bioactive and imaging agents. PMID:21128624

  19. 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

  20. 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.

  1. 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.

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  3. Two for the Price of One: PAMAM-Dendrimers with Mixed Phosphoryl Choline and Oligomeric Poly(Caprolactone) Surfaces.

    Science.gov (United States)

    Svenningsen, Søren Wedel; Janaszewska, Anna; Ficker, Mario; Petersen, Johannes Fabritius; Klajnert-Maculewicz, Barbara; Christensen, Jørn Bolstad

    2016-06-15

    The application of dendrimers for biological and medical purposes is highly dependent on the type of surface group in relation to cytotoxicity. Since amine terminated PAMAM dendrimers have been shown to have toxic properties and thereby limited applications in the medical field, the discovery of a new nontoxic surface coating is of great interest. In the present work, amine terminated DAB-PAMAM dendrimers from generation zero to four have been coated with statistical surface functionalization giving a dendrimer surface consisting of an approximately 1:1 mixture of zwitterionic phosphoryl choline hexanamide and 6-((6-hydroxyhexanoyl)oxy)hexanamide. The cytotoxic properties of generation two to four were tested on three different human cancer cell lines, SKBR3 human breast cancer cells, HeLa human cervical cancer cells, and Hep G2 human hepatocellular liver carcinoma cells and compared to the toxicity of amine terminated PAMAM dendrimers. In addition to lower cytotoxicity than observed for amine terminated dendrimers, the coated dendrimers showed minor cytotoxicity against all three human cell lines, negligible influence on ROS generation and mitochondrial membrane potential. These observations support the conclusion that the analyzed group of phosphorylcholine dendrimers may be suitable for medical applications.

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

    Science.gov (United States)

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

    2017-08-30

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

  5. COMPARATIVE PHARMACOKINETICS OF PAMAM-OH DENDRIMERS AND HPMA COPOLYMERS IN OVARIAN-TUMOR-BEARING MICE.

    Science.gov (United States)

    Sadekar, S; Linares, O; Noh, Gj; Hubbard, D; Ray, A; Janát-Amsbury, M; Peterson, C M; Facelli, J; Ghandehari, H

    2013-06-01

    The purpose of this study was to model data from a head to head comparison of the in vivo fate of hyper-branched PAMAM dendrimers with linear HPMA copolymers in order to understand the influence of molecular weight (MW), hydrodynamic size (Rh) and polymer architecture on biodistribution in tumor-bearing mice using compartmental pharmacokinetic analysis. Plasma concentration data was modeled by two-compartment analysis using Winnonlin® to obtain elimination clearance (E.CL) and plasma exposure (AUCplasma). Renal clearance (CLR) was calculated from urine data collected over 1 week. A plasma-tumor link model was fitted to experimental plasma and tumor data by varying the tumor extravasation (K4, K6) and elimination (K5) rate constants using multivariable constrained optimization solver in Matlab®. Tumor exposures (AUCtumor) were computed from area under the tumor concentration time profile curve by the linear trapezoidal method. Along with MW and Rh, polymer architecture was critical in affecting the blood and tumor pharmacokinetics of the PAMAM-OH dendrimers and HPMA copolymers. Elimination clearance decreased more rapidly with increase in hydrodynamic size for PAMAM-OH dendrimers as compared to HPMA copolymers. HPMA copolymers were eliminated renally to a higher extent than PAMAM-OH dendrimers. These results are suggestive of a difference in extravasation of polymers of varying architecture through the glomerular basement membrane. While the linear HPMA copolymers can potentially reptate through a pore smaller in size than their hydrodynamic radii in a random coil conformation, PAMAM dendrimers have to deform in order to permeate across the pores. With increase in molecular weight or generation, the deforming capacity of PAMAM-OH dendrimers is known to decrease, making it harder for higher generation PAMAM-OH dendrimers to sieve through the glomerulus as compared to HPMA copolymers of comparable molecular weights. PAMAM-OH dendrimer had greater tumor extravsation

  6. Uniform brain tumor distribution and tumor associated macrophage targeting of systemically administered dendrimers.

    Science.gov (United States)

    Zhang, Fan; Mastorakos, Panagiotis; Mishra, Manoj K; Mangraviti, Antonella; Hwang, Lee; Zhou, Jinyuan; Hanes, Justin; Brem, Henry; Olivi, Alessandro; Tyler, Betty; Kannan, Rangaramanujam M

    2015-06-01

    Effective blood-brain tumor barrier penetration and uniform solid tumor distribution can significantly enhance therapeutic delivery to brain tumors. Hydroxyl-functionalized, generation-4 poly(amidoamine) (PAMAM) dendrimers, with their small size, near-neutral surface charge, and the ability to selectively localize in cells associated with neuroinflammation may offer new opportunities to address these challenges. In this study we characterized the intracranial tumor biodistribution of systemically delivered PAMAM dendrimers in an intracranial rodent gliosarcoma model using fluorescence-based quantification methods and high resolution confocal microscopy. We observed selective and homogeneous distribution of dendrimer throughout the solid tumor (∼6 mm) and peritumoral area within fifteen minutes after systemic administration, with subsequent accumulation and retention in tumor associated microglia/macrophages (TAMs). Neuroinflammation and TAMs have important growth promoting and pro-invasive effects in brain tumors. The rapid clearance of systemically administered dendrimers from major organs promises minimal off-target adverse effects of conjugated drugs. Therefore, selective delivery of immunomodulatory molecules to TAM, using hydroxyl PAMAM dendrimers, may hold promise for therapy of glioblastoma. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2016-12-01

    The binding behavior of nanoparticle with proteins determines its biocompatibility. This study reports the interaction of ten different biomolecules (proteins-BSA, HSA, haemoglobin, gamma globulin, transferrin and enzymes-hog and bacillus amylase, lysozyme from chicken and human and laccases from Tramates versicolor) with a surface group hydroxylated Poly AMido AMide dendrimer (PAMAM) of generation 5. The study has utilized various spectroscopic methods like UV-vis spectroscopy, Fluorescence emission, Synchronous, 3-D spectroscopy and Circular Dichroism to detect the binding induced structural changes in biomolecules that occur upon interaction with mounting concentration of the dendrimers. Aggregation of proteins results in the formation of amyloid fibrils causing several human diseases. In this study, fibrillar samples of all ten biomolecules formed in the absence and the presence of dendrimers were investigated with Congo Red absorbance and ThT Assay to detect fibril formation, Trp Emission and 3-D scan to evaluate the effect of fibrillation on aromatic environment of biomolecules, and CD spectroscopy to measure the conformational changes in a quantitative manner. These assays have generated useful information on the role of dendrimers in amyloid fibril formation of biomolecules. The outcomes of the study remain valuable in evaluating the biological safety of PAMAM-OH dendrimers for their biomedical application in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Nanoparticle size and surface charge determine effects of PAMAM dendrimers on human platelets in vitro

    Science.gov (United States)

    Dobrovolskaia, Marina A.; Patri, Anil K.; Simak, Jan; Hall, Jennifer B.; Semberova, Jana; De Paoli Lacerda, Silvia H.; McNeil, Scott E.

    2013-01-01

    Blood platelets are essential in maintaining hemostasis. Various materials can activate platelets and cause them to aggregate. Platelet aggregation in vitro is often used as a marker for materials’ thrombogenic properties and studying nanomaterial interaction with platelets is an important step toward understanding their hematocompatibility. Here we report evaluation of 12 formulations of PAMAM dendrimers varying in size and surface charge. Using a cell counter based method, light transmission aggregometry and scanning electron microscopy, we show that only large cationic dendrimers, but not anionic, neutral or small cationic dendrimers, induce aggregation of human platelets in plasma in vitro. The aggregation caused by large cationic dendrimers was proportional to the number of surface amines. The observed aggregation was not associated with membrane microparticle release, and was insensitive to a variety of chemical and biological inhibitors known to interfere with various pathways of platelet activation. Taken in context with previously reported studies, our data suggest that large cationic PAMAM dendrimers induce platelet aggregation through disruption of membrane integrity. PMID:22026635

  9. Gene delivery efficiency and cytotoxicity of heterocyclic amine-modified PAMAM and PPI dendrimers.

    Science.gov (United States)

    Hashemi, Maryam; Tabatabai, Seyed Meghdad; Parhiz, Hamideh; Milanizadeh, Soroush; Amel Farzad, Sara; Abnous, Khalil; Ramezani, Mohammad

    2016-04-01

    Poly-(amidoamine) (PAMAM) and poly-(propylenimine) (PPI) are the two most widely investigated dendrimers for drug and gene delivery. In order to enhance DNA transfection activity of these dendrimers, generation 3 and 4 PAMAM and generation 4 and 5 PPI were modified by partial substitution of surface primary amines with histidine, pyridine, and piperazine, which have buffering capacity properties. It was shown that higher dendrimer generations and higher grafting percentages (30% and 50% of primary amines) were associated with higher transfection activity. Pyridine was the most effective substituent for PPI, while piperazine-modified PAMAM dendrimers showed the best transfection efficiency among PAMAM-based vectors in murine neuroblastoma (Neuro-2a) cells. None of the modified carriers showed remarkable cytotoxicity in vitro. Pretreatment of cells with bafilomycin A indicated that endosomal buffering capacity is the main mechanism of endosomal escape. In conclusion, PAMAM and PPI may exhibit different gene delivery efficiency and cytotoxicity profiles with the same chemical modifications. These modified dendrimers could be considered as efficient and safe gene carriers in neuroblastoma cells in vitro. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Valeria Márquez-Miranda

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

  11. α-Conotoxin dendrimers have enhanced potency and selectivity for homomeric nicotinic acetylcholine receptors.

    Science.gov (United States)

    Wan, Jingjing; Huang, Johnny X; Vetter, Irina; Mobli, Mehdi; Lawson, Joshua; Tae, Han-Shen; Abraham, Nikita; Paul, Blessy; Cooper, Matthew A; Adams, David J; Lewis, Richard J; Alewood, Paul F

    2015-03-11

    Covalently attached peptide dendrimers can enhance binding affinity and functional activity. Homogenous di- and tetravalent dendrimers incorporating the α7-nicotinic receptor blocker α-conotoxin ImI (α-ImI) with polyethylene glycol spacers were designed and synthesized via a copper-catalyzed azide-alkyne cycloaddition of azide-modified α-ImI to an alkyne-modified polylysine dendron. NMR and CD structural analysis confirmed that each α-ImI moiety in the dendrimers had the same 3D structure as native α-ImI. The binding of the α-ImI dendrimers to binding protein Ac-AChBP was measured by surface plasmon resonance and revealed enhanced affinity. Quantitative electrophysiology showed that α-ImI dendrimers had ∼100-fold enhanced potency at hα7 nAChRs (IC50 = 4 nM) compared to native α-ImI (IC50 = 440 nM). In contrast, no significant potency enhancement was observed at heteromeric hα3β2 and hα9α10 nAChRs. These findings indicate that multimeric ligands can significantly enhance conotoxin potency and selectivity at homomeric nicotinic ion channels.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Huang, Weizhe; He, Ziying

    2013-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jiangyu Wu

    2013-01-01

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

  16. 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.

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

    Science.gov (United States)

    Zhang, Zhida; Feng, Shengyu; Zhang, Jie

    2016-02-01

    A combination of a thiol-Michael addition reaction and a free radical mediated thiol-ene reaction is employed as a facile and efficient approach to carbosiloxane dendrimer synthesis. For the first time, carbosiloxane dendrimers are constructed rapidly by an orthogonal click strategy without protection/deprotection procedures. The chemoselectivity of these two thiol-ene click reactions leads to a design of a new monomer containing both electron-deficient carbon-carbon double bonds and unconjugated carbon-carbon double bonds. Siloxane bonds are introduced as the linker between these two kinds of carbon-carbon double bonds. Starting from a bifunctional thiol core, the dendrimers are constructed by iterative thiol-ene click reactions under different but both mild reaction conditions. After simple purification steps the fifth dendrimer with 54 peripheral functional groups is obtained with an excellent overall yield in a single day. Furthermore, a strong blue glow is observed when the dendrimer is excited by a UV lamp. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Synthesis and Application of Injectable Bioorthogonal Dendrimer Hydrogels for Local Drug Delivery.

    Science.gov (United States)

    Xu, Leyuan; Cooper, Remy C; Wang, Juan; Yeudall, W Andrew; Yang, Hu

    2017-08-14

    We developed novel dendrimer hydrogels (DH)s on the basis of bioorthogonal chemistry, in which polyamidoamine (PAMAM) dendrimer generation 4.0 (G4) functionalized with strained alkyne dibenzocyclooctyne (DBCO) via PEG spacer (Mn = 2,000 g/mol) underwent strain-promoted azide-alkyne cycloaddition (SPAAC) with polyethylene glycol bisazide (PEG-BA) (Mn= 20,000 g/mol) to generate a dendrimer-PEG cross-linked network. This platform offers a high degree of functionality and modularity. A wide range of structural parameters including dendrimer generation, degree of PEGylation, loading density of clickable DBCO groups, PEG-BA chain length as well as the ratio of clickable dendrimer to PEG-BA and their concentrations can be readily manipulated to tune chemical and physical properties of DHs. We used this platform to prepare an injectable liquid DH. This bioorthogonal DH exhibited high cytocompatibility and enabled sustained release of the anticancer drug 5-fluorouracil (5-FU). Following intratumoral injection, the DH/5-FU formulation significantly suppressed tumor growth and improved survival of HN12 tumor-bearing mice by promoting tumor cell death as well as by reducing tumor cell proliferation and angiogenesis.

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

    KAUST Repository

    Wang, Shuaipeng

    2014-10-27

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

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

    Science.gov (United States)

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

    2016-04-15

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

  1. NMR relaxation of the orientation of single segments in semiflexible dendrimers

    Energy Technology Data Exchange (ETDEWEB)

    Markelov, Denis A., E-mail: markeloved@gmail.com; Gotlib, Yuli Ya. [Faculty of Physics, St. Petersburg State University, Ulyanovskaya Str. 1, Petrodvorets, St. Petersburg, 198504 (Russian Federation); Institute of Macromolecular Compounds, Russian Academy of Sciences, Bolshoy pr. 31, V.O., St. Petersburg, 199004 (Russian Federation); Dolgushev, Maxim; Blumen, Alexander [Theoretical Polymer Physics, University of Freiburg, Hermann-Herder-Str. 3, D-79104 Freiburg (Germany)

    2014-06-28

    We study the orientational properties of labeled segments in semiflexible dendrimers making use of the viscoelastic approach of Dolgushev and Blumen [J. Chem. Phys. 131, 044905 (2009)]. We focus on the segmental orientational autocorrelation functions (ACFs), which are fundamental for the frequency-dependent spin-lattice relaxation times T{sub 1}(ω). We show that semiflexibility leads to an increase of the contribution of large-scale motions to the ACF. This fact influences the position of the maxima of the [1/T{sub 1}]-functions. Thus, going from outer to inner segments, the maxima shift to lower frequencies. Remarkably, this feature is not obtained in the classical bead-spring model of flexible dendrimers, although many experiments on dendrimers manifest such a behavior.

  2. Influence of Structural Parameters on the Self-Association Properties of Anti-HIV Catanionic Dendrimers.

    Science.gov (United States)

    Perez-Anes, Alexandra; Rodrigues, Fernanda; Caminade, Anne-Marie; Stefaniu, Cristina; Tiersch, Brigitte; Turrin, Cédric-Olivier; Blanzat, Muriel

    2015-11-16

    The self-association properties of anti-HIV catanionic dendrimers as multivalent galactosylceramide (GalCer)-derived inhibitors are presented. The study was designed to elucidate the origin of the relatively high cytotoxicity values of these anti-HIV catanionic dendrimers, which have previously been found to exhibit in vitro anti-HIV activity in the submicromolar range. The physicochemical properties of these catanionic dendrimers were studied to tentatively correlate the structural parameters with self-association and biological properties. We can conclude from this study that the absence of correlation between the hydrophobicity and the cytotoxicity of the catanionic systems could be explained by the partial segregation of the different partners of the catanionic entities. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Controlling Cellular Uptake and Toxicity of Polyphenylene Dendrimers by Chemical Functionalization.

    Science.gov (United States)

    Hammer, Brenton A G; Wu, Yuzhou; Fischer, Stephan; Liu, Weina; Weil, Tanja; Müllen, Klaus

    2017-05-18

    Polyphenylene dendrimers (PPDs) represent a unique class of macromolecules based on their monodisperse and shape-persistent nature. These characteristics have enabled the synthesis of a new genre of "patched" surface dendrimers, where their exterior can be functionalized with a variety of polar and nonpolar substituents to yield lipophilic binding sites in a site-specific way. Although such materials are capable of complexing biologically relevant molecules, show high cellular uptake in various cell lines, and low to no toxicity, there is minimal understanding of the driving forces to these characteristics. We investigated whether it is the specific chemical functionalities, relative quantities of each moiety, or the "patched" surface patterning on the dendrimers that more significantly influences their behavior in biological media. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Novel perfluorocyclobutane (PFCB)-containing polymers and dendrimers for photonic devices

    Science.gov (United States)

    Ma, Hong; Wong, Sharon; Kang, Seok H.; Luo, Jingdong; Haller, Marnie; Jen, Alex K. Y.; Barto, Richard R.; Frank, Curtis W.

    2002-11-01

    A wide variety of aromatic trifluorovinyl ether monomers and highly fluorinated crosslinkable dendrimers have been developed via novel synthetic strategies. Through the thermal dimerization of trifluorovinyl ether moieties on the monomers or on the periphery of dendrimers, these monomers or dendrimers can be melt or solution polymerized to form perfluorocyclobutane(PFCB)-containing prepolymers with good processability for optical waveguide fabrication. By further thermal crosslinking, the resulting thermoset materials possess low optical loss (0.3-0.4 dB/cm at 1310 nm with 1% of DR-1 or DCM doping), high thermal stability (Tg: 100-400 °C), good thermo-optic property, high solvent and humid resistance, and excellent mechanical flexibility. The combination of processability and performance in these PFCB-containing thermoset materials make them as ideal candidates for the fabrication of high-performance polymeric planar lightwave circuit components with the applications in the telecom and datacom optical networks.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-07-23

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

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

    Science.gov (United States)

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

    2014-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Gerhart Jacquelyn

    2004-01-01

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

  8. Hyperbranched polymers and dendrimers as templates for organic/inorganic hybrid nanomaterials.

    Science.gov (United States)

    Huang, Xinhua; Zheng, Sudan; Kim, Il

    2014-02-01

    This paper reviews the recent research and development of hyperbranched polymers (HPs) and dendrimers, and their use as templates for organic-inorganic hybrid nanomaterials. Hyperbranched polymers (HPs) are highly branched macromolecules with three-dimensional globular structures featuring unique properties such as low viscosity, high solubility, and a large number of terminal functional groups compared to their linear analogs. They are easily prepared by (1) condensation polymerization, (2) self-condensing vinyl copolymerization (SCVCP), and (3) ring-opening multibranch polymerization methods. Organic-inorganic hybrid nanomaterials are synthesized by a template approach using HPs/dendrimers. Monometallic, bimetallic (alloy and core/shell), semiconductor, and metal oxide nanoparticles have been prepared by this route. The dendrimer component of these composites serves not only as a template for preparing the nanoparticles but also as a stabilizer for the nanoparticles.

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

    Directory of Open Access Journals (Sweden)

    Sadik Kaga

    2016-04-01

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

  10. Electron injection from graphene quantum dots to poly(amido amine) dendrimers

    Energy Technology Data Exchange (ETDEWEB)

    Lin, T. N.; Inciong, M. R.; Santiago, S. R.; Shu, G. W.; Yuan, C. T.; Shen, J. L., E-mail: jlshen@cycu.edu.tw [Department of Physics, Center for Nanotechnology, and Center for Biomedical Technology, Chung Yuan Christian University, Chung-Li 32023, Taiwan (China); Kao, C. W. [Master Program in Nanotechnology at CYCU, Chung Yuan Christian University, Chung-Li 32023, Taiwan (China); Yeh, J. M.; Chen-Yang, Y. W. [Department of Chemistry, Center for Nanotechnology, and Center for Biomedical Technology, Chung Yuan Christian University, Chung-Li 32023, Taiwan (China)

    2016-04-18

    The steady-state and time-resolved photoluminescence (PL) are used to study the electron injection from graphene quantum dots (GQDs) to poly(amido amine) (PAMAM) dendrimers. The PL is enhanced by depositing GQDs on the surfaces of the PAMAM dendrimers. The maximum enhancement of PL with a factor of 10.9 is achieved at a GQD concentration of 0.9 mg/ml. The dynamics of PL in the GQD/PAMAM composite are analyzed, evidencing the existence of electron injection. On the basis of Kelvin probe measurements, the electron injection from the GQDs to the PAMAM dendrimers is accounted for by the work function difference between them.

  11. EXAFS Characterization of Dendrimer-Derived Pt/γ-Al2O3

    Science.gov (United States)

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

    2007-02-01

    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 Å 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.

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

    Science.gov (United States)

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

    2015-11-01

    The aim of the present investigation was to deliver Gemcitabine Hydrochloride (GmcH), an anticancer bioactive, specifically to lung tumor cells using mannosylated 4.0G poly(propyleneimine) dendrimers (M-PPI). 4.0G poly(propyleneimine) (PPI) dendrimers was synthesized using ethylenediamine as core and conjugated with mannose by ring opening reactions, followed by Schiff's reaction in the presence of sodium acetate buffer (pH 4.0). Synthesized PPI dendrimers and mannose-conjugated dendrimers were characterized using IR, NMR spectroscopy, and scanning electron microscopy. GmcH was loaded into PPI and M-PPI dendrimers using equilibrium dialysis method to develop the formulations, GmcH-PPI and GmcH-M-PPI, respectively. The developed formulations were evaluated for drug loading, in vitro release kinetics, in vitro stability, hemolytic toxicity, cytotoxicity, pharmacokinetic, and biodistribution studies. The dendrimeric formulation of GmcH showed pH-sensitive release with faster release at acidic pH, i.e., pH 4.0 in comparison with physiological pH 7.4. M-PPI conjugate showed significant reduction in hemolytic toxicity as compared to plain 4.0G PPI dendrimers towards human erythrocytes. In the cytotoxicity studies with A-549 lung adenocarcinoma cell line, the GmcH-M-PPI formulation showed the lowest IC50 value. Further, the pharmacokinetic and tissue distribution studies of free drug GmcH, GmcH-PPI, and GmcH-M-PPI in albino rats of Sprague-Dawley strain suggested the mean residence time of GmcH-M-PPI conjugate to be significantly higher (24.85 h) than free GmcH and GmcH-PPI. Deposition of drug (396.1 ± 4.7 after 2 h) in lung was found to be significantly higher with GmcH-M-PPI formulation in comparison with Gmch and GmcH-PPI.

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

    Science.gov (United States)

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

    2015-01-01

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

  14. Multivalent dendrimers presenting spatially controlled clusters of binding epitopes in thermoresponsive hyaluronan hydrogels.

    Science.gov (United States)

    Seelbach, Ryan J; Fransen, Peter; Peroglio, Marianna; Pulido, Daniel; Lopez-Chicon, Patricia; Duttenhoefer, Fabian; Sauerbier, Sebastian; Freiman, Thomas; Niemeyer, Philipp; Semino, Carlos; Albericio, Fernando; Alini, Mauro; Royo, Miriam; Mata, Alvaro; Eglin, David

    2014-10-01

    The controlled presentation of biofunctionality is of key importance for hydrogel applications in cell-based regenerative medicine. Here, a versatile approach was demonstrated to present clustered binding epitopes in an injectable, thermoresponsive hydrogel. Well-defined multivalent dendrimers bearing four integrin binding sequences and an azido moiety were covalently grafted to propargylamine-derived hyaluronic acid (Hyal-pa) using copper-catalyzed alkyne-azide cycloaddition (CuAAC), and then combined with pN-modified hyaluronan (Hyal-pN). The dendrimers were prepared by synthesizing a bifunctional diethylenetriamine pentaacetic acid core with azido and NHBoc oligo(ethylene glycol) aminoethyl branches, then further conjugated with solid-phase synthesized RGDS and DGRS peptides. Azido terminated pN was synthesized by reversible addition-fragmentation chain transfer polymerization and reacted to Hyal-pa via CuAAC. Nuclear magnetic resonance (NMR), high performance liquid chromatography, size exclusion chromatography and mass spectroscopy proved that the dendrimers had well-defined size and were disubstituted. NMR and atomic absorption analysis confirmed the hyaluronan was affixed with dendrimers or pN. Rheological measurements demonstrated that dendrimers do not influence the elastic or viscous moduli of thermoresponsive hyaluronan compositions at a relevant biological concentration. Finally, human mesenchymal stromal cells were encapsulated in the biomaterial and cultured for 21days, demonstrating the faculty of this dendrimer-modified hydrogel as a molecular toolbox for tailoring the biofunctionality of thermoresponsive hyaluronan carriers for biomedical applications. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  15. White organic light emitting diodes based on fluorene-carbazole dendrimers

    Energy Technology Data Exchange (ETDEWEB)

    Usluer, Özlem, E-mail: usluerozlem@yahoo.com.tr [Department of Chemistry, Muğla Sıtkı Koçman University, 48000 Muğla (Turkey); Demic, Serafettin [Department of Materials Science and Engineering, Izmir Katip Çelebi University, 35620 Çiğli, Izmir (Turkey); Kus, Mahmut, E-mail: mahmutkus1@gmail.com [Chemical Engineering Department and Advanced Technology R and D Center, Selçuk University, Konya (Turkey); Özel, Faruk [Chemical Engineering Department and Advanced Technology R and D Center, Selçuk University, Konya (Turkey); Serdar Sariciftci, Niyazi [Linz Institute for Organic Solar Cells (LIOS), Physical Chemistry, Johannes Kepler University, Altenbergerstr. 69, A-4040 Linz (Austria)

    2014-02-15

    In this paper, we report on theProd. Type: FTP fabrication and characterization of blue and white light emitting devices based on two fluorene-carbazole containing dendrimers and para-sexiphenyl (6P) oligomers. Blue light emitting diodes were fabricated using 9′,9″-(9,9-dioctyl-9H-fluorene-2,7-diyl)bis-9′H-9,3′:6′,9″-tercarbazole (OFC-G2) and 9′,9″-(9,9′-spirobi[fluorene]-2,7-diyl)bis-9′H-9,3′:6′,9″-tercarbazole (SBFC-G2) dendrimers as a hole transport and emissive layer (EML) and 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline (BCP) as an electron transport layer. White light emitting diodes were fabricated using 6P and these two dendrimers as an EML. OLED device with the structure of ITO/PEDOT:PSS (50 nm)/OFC-G2 (40 nm)/6P (20 nm)/LiF:Al (0.5:100 nm) shows maximum luminance of nearly 1400 cd/m{sup 2} and a Commission Internationale de l'Eclairage chromaticity coordinates of (0.27, 0.30) at 12 V. -- Highlights: • White organic light emitting diodes have been fabricated using two fluorene-carbazole dendrimers and para-sexiphenyl (6P) oligomers. • When only these two dendrimers are used as EML, OLED devices are emitted blue light. • The emission colors of OLED devices change from blue to white when 6P is coated on dendrimer films.

  16. Manganese G8 dendrimers targeted to oxidation-specific epitopes: in vivo MR imaging of atherosclerosis.

    Science.gov (United States)

    Nguyen, Tuyen H; Bryant, Henry; Shapsa, Ari; Street, Hannah; Mani, Venkatesh; Fayad, Zahi A; Frank, Joseph A; Tsimikas, Sotirios; Briley-Saebo, Karen C

    2015-03-01

    To determine if manganese (Mn) G8 dendrimers targeted to oxidation-specific epitopes (OSE) allow for in vivo detection of atherosclerotic lesions. OSE have been identified as key factors in atherosclerotic plaque progression and destabilization. Mn offers a potentially clinically translatable alternative to gadolinium-based agents when bioretention and potential toxicity of gadolinium is anticipated. However, to be effective, high payloads of Mn must accumulate intracellularly in macrophages. It was hypothesized that G8 dendrimers targeted to OSE may allow delivery of high Mn payloads, thereby enabling in vivo detection of macrophage-rich plaques. G8 dendrimers were modified to allow conjugation with MnDTPA (758 Mn ion) and the antibody MDA2 that is targeted to malondialdehyde (MDA)-lysine epitopes. Both the untargeted and targeted G8 dendrimers were characterized and their in vivo efficacy evaluated in apoE(-/-) mice over a 96-hour time period after bolus administration of a 0.05 mmol Mn/kg dose using a clinical MR system (3T). Significant enhancement (normalized enhancement >60%, P = 0.0013) of atherosclerotic lesions was observed within a 72-hour time period following administration of the targeted dendrimers. The presence of Mn within atherosclerotic lesions was confirmed using spectroscopic methods (>8 μg Mn/g). Limited signal attenuation (<18%) and Mn deposition (<1 μg Mn/g) was observed in the arterial wall following injection of the untargeted material. This study demonstrates that manganese-labeled dendrimers, allowing a high Mn payload, targeted to OSE may allow in vivo image of atherosclerotic lesions. © 2014 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Osman NAMIRTI

    2011-02-01

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

  18. Drug delivery using multifunctional dendrimers and hyperbranched polymers.

    Science.gov (United States)

    Paleos, Constantinos M; Tsiourvas, Dimitris; Sideratou, Zili; Tziveleka, Leto-Aikaterini

    2010-12-01

    The review presents the design strategy and synthesis of multifunctional dendrimers and hyperbranched polymers with the objective to develop effective drug delivery systems. Well-characterized, commercially available dendritic polymers were subjected to functionalization for preparing drug delivery systems of low toxicity, high loading capacity, ability to target specific cells and transport through their membranes. This has been achieved by surface targeting ligands, which render the carriers specific to certain cells and polyethylene glycol groups, securing water solubility, stability and prolonged circulation. Moreover, transport agents facilitate transport through cell membranes while fluorescent probes detect their intracellular localization. A common feature of surface groups is multivalency, which considerably enhances their binding strength with complementary cell receptors. To these properties, one should also add the property of attaining high loading of active ingredients coupled with controlled and/or triggered release. Readers will be exposed to the strategy of synthesizing multifunctional polymers, aimed at the development of effective drug delivery systems. Multifunctional systems upgrade the therapeutic potential of drugs and, in certain cases, may even lead to the application of new bioactive compounds that would otherwise not be feasible.

  19. UV luminescence of dendrimer-encapsulated gold nanoclusters

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Hyeong Seop; Kim, Jun Myung; Sohn, So Hyeong; Han, Noh Soo; Park, Seung Min [Dept. of Chemistry, Kyung Hee University, Seoul (Korea, Republic of)

    2016-10-15

    Size-dependent luminescence color is one of the interesting properties of metal nanocrystals, whose sizes are in the dimension of the Fermi wavelength of an electron. Despite the short Fermi wavelength of electrons in gold (-0.7 nm), luminescence of gold nanoclusters has been reported to range from the near-infrared to near-ultraviolet, depending on the number of atoms in the nanoclusters. The photoluminescence of G4-OH (Au) obtained by the excitation of 266 nm showed UV emission in addition to the well-known blue emission. The higher intensity and red-shifted emission of the gold nanoclusters was distinguished from the emission of dendrimers. The UV emission at 352 nm matched the emission energy of Au{sub 4} in the spherical jellium model, rather than the planar Au{sub 8}, which supported the emission of Au{sub 4} formed in G4-OH. Despite the change of [HAuCl{sub 4} ]/[G4-OH], the relative population between Au{sub 4} and Au{sub 8} was similar in G4-OH(Au), which indicated that the closed electronic and geometric structures stabilized the magic number of Au{sub 4}.

  20. Dendrimer-like hybrid particles with tunable hierarchical pores

    Science.gov (United States)

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

    2015-03-01

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

  1. Trastuzumab-grafted PAMAM dendrimers for the selective delivery of anticancer drugs to HER2-positive breast cancer.

    Science.gov (United States)

    Kulhari, Hitesh; Pooja, Deep; Shrivastava, Shweta; Kuncha, Madhusudana; Naidu, V G M; Bansal, Vipul; Sistla, Ramakrishna; Adams, David J

    2016-04-07

    Approximately 20% of breast cancer cases are human epidermal growth factor receptor 2 (HER2)-positive. This type of breast cancer is more aggressive and tends to reoccur more often than HER2-negative breast cancer. In this study, we synthesized trastuzumab (TZ)-grafted dendrimers to improve delivery of docetaxel (DTX) to HER2-positive breast cancer cells. Bioconjugation of TZ on the surface of dendrimers was performed using a heterocrosslinker, MAL-PEG-NHS. For imaging of cancer cells, dendrimers were also conjugated to fluorescein isothiocyanate. Comparative in vitro studies revealed that these targeted dendrimers were more selective, and had higher antiproliferation activity, towards HER2-positive MDA-MB-453 human breast cancer cells than HER2-negative MDA-MB-231 human breast cancer cells. When compared with unconjugated dendrimers, TZ-conjugated dendrimers also displayed higher cellular internalization and induction of apoptosis against MDA-MB-453 cells. Binding of TZ to the dendrimer surface could help site-specific delivery of DTX and reduce systemic toxicity resulting from its lack of specificity. In addition, in vivo studies revealed that the pharmacokinetic profile of DTX was significantly improved by the conjugated nanosystem.

  2. Internalization and Subcellular Trafficking of Poly-l-lysine Dendrimers Are Impacted by the Site of Fluorophore Conjugation.

    Science.gov (United States)

    Avaritt, Brittany R; Swaan, Peter W

    2015-06-01

    Internalization and intracellular trafficking of dendrimer-drug conjugates play an important role in achieving successful drug delivery. In this study, we aimed to elucidate the endocytosis mechanisms and subcellular localization of poly-l-lysine (PLL) dendrimers in Caco-2 cells. We also investigated the impact of fluorophore conjugation on cytotoxicity, uptake, and transepithelial transport. Oregon green 514 (OG) was conjugated to PLL G3 at either the dendrimer periphery or the core. Chemical inhibitors of clathrin-, caveolin-, cholesterol-, and dynamin-mediated endocytosis pathways and macropinocytosis were employed to establish internalization mechanisms, while colocalization with subcellular markers was used to determine dendrimer trafficking. Cell viability, internalization, and uptake were all influenced by the site of fluorophore conjugation. Uptake was found to be highly dependent on cholesterol- and dynamin-mediated endocytosis as well as macropinocytosis. Dendrimers were trafficked to endosomes and lysosomes, and subcellular localization was impacted by the fluorophore conjugation site. The results of this study indicate that PLL dendrimers exploit multiple pathways for cellular entry, and internalization and trafficking can be impacted by conjugation. Therefore, design of dendrimer-drug conjugates requires careful consideration to achieve successful drug delivery.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-06-18

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

  4. 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-NH2) and fifth generation of poly (propylene) imine dendrimers (G5-PPI-NH2). It was observed that aqueous solubility of BTZ was concentration and pH dependent. At 2mM G5-PPI-NH2 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 (pthermodynamic 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.

  5. Novel Antimicrobial Peptide Dendrimers with Amphiphilic Surface and Their Interactions with Phospholipids — Insights from Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Paulina Zielinska

    2013-06-01

    Full Text Available A series of new peptide dendrimers with amphiphilic surface, designed around a dendronized ornithine (Orn core were synthesized and characterized by ESI-MS, 1H-, 13C- NMR, and CD spectrometry. An improved antimicrobial potency against S. aureus and E. coli was detected as a result of an increased charge, higher branching and variable lipophilicity of the residues located at the C-terminus. Minimal inhibitory concentration (MIC values indicated that the selected dendrimers were not sensitive to the physiological concentration of Na+ and K+ ions (100 mM, but expressed reduced potency at 10 mM concentration of Mg2+ and Ca2+ ions. Circular dichroism (CD curves measured under various conditions revealed structure and solvent-dependent curve evolution. ESI-MS studies of gas-phase interactions between selected dendrimers and both anionic (DMPG and neutral (DMPC phospholipids revealed the presence of variously charged dendrimer/phospholipid aggregates with 1:1 to 1:5 stoichiometry. The collision-induced fragmentation (CID of the most abundant [dendrimer/phospholipid]2+ ions of the 1:1 stoichiometry demonstrated that the studied dendrimers formed stronger complexes with anionic DMPG. Both phospholipids have higher affinity towards dendrimers with a more compact structure. Higher differences in CID energy necessary for dissociation of 50% of the complex formed by dendrimers with DMPG vs. DMPC (DCID50 correlate with a lower hemotoxicity. Mass spectrometry results suggest that for a particular group of compounds the DCID50 might be one of the important factors explaining selectivity of antimicrobial peptides and their branched analogs targeting the bacterial membrane. Both circular dichroism and mass spectrometry studies demonstrated that dendrimers of Nα- and Nε-series possess a different conformation in solution and different affinity to model phospholipids, what might influence their specific microbicidal mechanism.

  6. 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...

  7. A one-pot synthesis of a 243-allyl dendrimer under ambient conditions.

    Science.gov (United States)

    Ornelas, Catia; Aranzaes, Jaime Ruiz; Cloutet, Eric; Astruc, Didier

    2006-06-22

    [reaction: see text] Hydrosilylation of a nonaallyl dendritic core using HSi(Me)(2)Cl followed by reaction with a phenolate dendronic brick bearing three allyl groups, followed by repetition of this sequence of reactions twice, allows a one-pot synthesis of a 243-allyl dendrimer under ambient conditions.

  8. Thiol-ene crosslinking polyamidoamine dendrimer-hyaluronic acid hydrogel system for biomedical applications.

    Science.gov (United States)

    Bi, Xiangdong; Liang, Aiye; Tan, Yu; Maturavongsadit, Panita; Higginbothem, Ashley; Gado, Togor; Gramling, Abigail; Bahn, Hanna; Wang, Qian

    2016-01-01

    A series of alkene functionalized polyamidoamine (PAMAM) dendrimers were synthesized to prepare in situ forming hydrogels with varied gelation time and mechanical properties through crosslinking with thiolated hyaluronic acid (HS-HA). By varying the alkenyl groups on the dendrimers, the gelation time displayed a large range from 8 seconds to 18 hours, and the modulus of the hydrogels ranged from 36 to 183 Pa under experimental conditions. Investigation by (1)H-NMR spectroscopy revealed that the gelation time and the stiffness of the hydrogels were governed by the degree of electron deficiency of alkenyl groups on the dendrimers. This research provided a systematic study on the relationship between chemical structures versus gelation time and mechanical properties of hydrogels, which could guide the way to synthesize in situ forming hydrogels with designated gelation time and stiffness for biomedical applications. Further, a RGD peptide was attached to the PAMAM dendrimers to enhance cell attachment and proliferation. Viability assays of Human Umbilical Vein Endothelial Cells (HUVEC) in the synthesized hydrogels demonstrated the biocompatibility of the hydrogels after 48 hours of culturing, and the RGD peptide improved the viability of HUVEC cells in hydrogels. We believe the PAMAM/HA hydrogel system is a tuneable and biocompatible system for diverse biomedical applications.

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

    Directory of Open Access Journals (Sweden)

    Mitra Gholami

    2016-06-01

    Conclusion: The NPAMAM-G7 dendrimer with end amine groups exhibited a positive impact on the removal of standard strains, gram-positive and gram-negative bacteria. Therefore, it is possible to use these nanodendrimers as antibacterial in the future.

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

    Science.gov (United States)

    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.

  11. A theoretical investigation of symmetry-origin unidirectional energy gradient in light-harvesting dendrimers

    Science.gov (United States)

    Koda, Shin-ichi

    2016-03-01

    We theoretically investigate a possibility that the symmetry of the repetitively branched structure of light-harvesting dendrimers creates the energy gradient descending toward inner generations (layers of pigment molecules) of the dendrimers. In the first half of this paper, we define a model system using the Frenkel exciton Hamiltonian that focuses only on the topology of dendrimers and numerically show that excitation energy tends to gather at inner generations of the model system at a thermal equilibrium state. This indicates that an energy gradient is formed in the model system. In the last half, we attribute this result to the symmetry of the model system and propose two symmetry-origin mechanisms creating the energy gradient. The present analysis and proposition are based on the theory of the linear chain (LC) decomposition [S. Koda, J. Chem. Phys. 142, 204112 (2015)], which equivalently transforms the model system into a set of one-dimensional systems on the basis of the symmetry of dendrimers. In the picture of the LC decomposition, we find that energy gradient is formed both in each linear chain and among linear chains, and these two mechanisms explain the numerical results well.

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

    Energy Technology Data Exchange (ETDEWEB)

    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 association of naphthalene with 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 materials in removing polycyclic aromatic hydrocarbon contaminants from water. Our experimental results indicate that graphene oxide 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 graphene oxide. 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 graphene oxide in removing naphthalene from water.

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

    Directory of Open Access Journals (Sweden)

    Maria Jimena Prieto

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

  14. Nanomechanical properties of hydroxyapatite (HAP) with DAB dendrimers (poly-propylene imine) coatings onto titanium surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Charitidis, Costas A., E-mail: charitidis@chemeng.ntua.gr [School of Chemical Engineering, National Technical University of Athens, Iroon Polytechniou, Zografou, 15780 Athens (Greece); Skarmoutsou, Amalia [School of Chemical Engineering, National Technical University of Athens, Iroon Polytechniou, Zografou, 15780 Athens (Greece); Tsetsekou, Athena; Brasinika, Despina [School of Mining Engineering and Metallurgy, National Technical University of Athens, Iroon Polytechniou, Zografou, 15780 Athens (Greece); Tsiourvas, Dimitris [National Centre for Scientific Research “Demokritos”, Institute of Physical Chemistry, Agia Paraskevi, 15310 Athens (Greece)

    2013-04-20

    Highlights: ► The synthesis of hydroxyapatite (HAP) nanoparticles in the presence of a cationic fourth generation diaminobutane poly(propylene imine) dendrimer (DAB). ► The nanomechanical properties of different HAP-DAB coatings onto titanium surfaces. ► Wear resistance and adhesion properties of the synthesized coatings quantified by nanoindentation data analysis. -- Abstract: Coatings of hydroxyapatite (HAP) nanorods onto titanium surfaces were synthesized with the aim to improve coatings’ mechanical properties and adhesion to the substrate. The coatings are consisting of HAP nanorods synthesized in the presence of a cationic fourth generation diaminobutane poly(propylene imine) dendrimer (DAB) bearing 32 amine end groups employing varying calcium: dendrimer ratios and varying hydrothermal treatments. The quality, surface morphology and structure of the coatings were characterized with X-ray diffraction, thermogravimetric analysis, scanning electron microscopy and energy dispersive microanalysis. Wear resistance and adhesion properties of the coatings onto titanium substrates were studied through nanoindentation analysis. The experimental conditions, namely the calcium: dendrimer molar ratio and the hydrothermal treatment temperature were carefully selected; thus, it was possible to produce coatings of high hardness and elastic modulus values (ranging between 1–4.5 GPa and 40–150 GPa, respectively) and/or high wear resistance and plastic deformation values.

  15. Identification of surface domain structure on enamel crystals using polyamidoamine dendrimer

    Science.gov (United States)

    Chen, Haifeng; Clarkson, Brian H.; Orr, Bradford; Majoros, Istvan; Banaszak Holl, Mark M.

    2002-03-01

    The control of hydroxyapatite crystal nucleation and crystal growth is central to the mineralization and remineralization of enamel and dentin of teeth. However, the precise biomolecular mechanisms involved remain obscure. The intimate association between the crystal's surface and extracellular protein components implies a modulating role for organic crystal interactions probably mediated via specific crystal surface domains. These include lattice defects and specific stereochemical arrays on associated organic molecules. The nature of protein-crystal interaction depends upon the physical forces of attraction / repulsion between specific biomolecular groups and crystal surface domains. The proposed study is to utilize specific polyamidoamine (PAMAM) dendrimers, also known as “artificial proteins”, acting as nanoprobe. These will be used to probe specific surface domain on the surface of the naturally derived crystals of hydroxyapatite and to determine how control of growth and dissolution may be affected at the biomolecular level. The hydroxyapatite crystals are extracted from the maturation stage enamel of rats. Three types of PAMAM dendrimers, respectively with amine-, carboxylic acid and methyl-capped surface, will be applied in the study. The dendrimer binding on the surface of the hydoxyapatite crystals will be characterized using atomic force microscopy (AFM). The different dendrimer binding on the crystals will disclose the specific surface domain structure on the crystals, which is assumed to be important in binding the extracellular protein.

  16. Dendrimer-Encapsulated Palladium Nanoparticles for Continuous-Flow Suzuki–Miyaura Cross-Coupling Reactions

    NARCIS (Netherlands)

    Ricciardi, R.; Huskens, Jurriaan; Holtkamp, M.; Karst, U.; Verboom, Willem

    2015-01-01

    Generation three, four, and five (G3, G4, and G5) poly(amidoamine) dendrimers were used for the encapsulation of palladium nanoparticles (Pd NPs) and their covalent anchoring within glass microreactors. G3-encapsulated Pd NPs showed the highest activity for a model Suzuki–Miyaura cross-coupling

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

    LENUS (Irish Health Repository)

    Chan, Jeffrey C Y

    2008-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Curtiss P Schneider

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

  19. 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 Pb2+, Hg2+, and Ni2+ and the harmless Ca2+ 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 Hg2+ 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.

  20. Ultrafast electronic energy relaxation in a conjugated dendrimer leading to inter-branch energy redistribution.

    Science.gov (United States)

    Ondarse-Alvarez, D; Kömürlü, S; Roitberg, A E; Pierdominici-Sottile, G; Tretiak, S; Fernandez-Alberti, S; Kleiman, V D

    2016-09-14

    Dendrimers are arrays of coupled chromophores, where the energy of each unit depends on its structure and conformation. The light harvesting and energy funneling properties are strongly dependent on their highly branched conjugated architecture. Herein, the photoexcitation and subsequent ultrafast electronic energy relaxation and redistribution of a first generation dendrimer (1) are analyzed combining theoretical and experimental studies. Dendrimer 1 consists of three linear phenylene-ethynylene (PE) units, or branches, attached in the meta position to a central group opening up the possibility of inter-branch energy transfer. Excited state dynamics are explored using both time-resolved spectroscopy and non-adiabatic excited state molecular dynamics simulations. Our results indicate a subpicosecond loss of anisotropy due to an initial excitation into several states with different spatial localizations, followed by exciton self-trapping on different units. This exciton hops between branches. The absence of an energy gradient leads to an ultrafast energy redistribution among isoenergetic chromophore units. At long times we observe similar probabilities for each branch to retain significant contributions of the transition density of the lowest electronic excited-state. The observed unpolarized emission is attributed to the contraction of the electronic wavefunction onto a single branch with frequent interbranch hops, and not to its delocalization over the whole dendrimer.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    to gold electrodes and labeled with methylene blue (MB), approached 267 s-1 and decreased as the packing density of dendrimers on the electrode surface was increased. A mechanistic analysis of the ET kinetics and fitting to the Marcus relationship showed that as the PAMAM surface coverage was increased...

  2. PAMAM Dendrimers as Potential Carriers of Gadolinium Complexes of Iminodiacetic Acid Derivatives for Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Magdalena Markowicz-Piasecka

    2015-01-01

    Full Text Available This is the first study describing the utilization of PAMAM dendrimers as delivery vehicles of novel magnetic resonance imaging (MRI contrast agents. The purpose of this paper was to establish the potential of G4 PAMAM dendrimers as carriers of gadolinium complexes of iminodiacetic acid derivatives and determine imaging properties of synthesized compounds in in vivo studies. Furthermore, we examined the influence of four synthesized complexes on the process of clot formation, stabilization, and lysis and on amidolytic activity of thrombin. Biodistribution studies have shown that the compounds composed of PAMAM G4 dendrimers and gadolinium complexes of iminodiacetic acid derivatives increase signal intensity preferably in liver in range of 59–116% in MRI studies which corresponds with the greatest accumulation of gadolinium after administration of the compounds. Synthesized compounds affect kinetic parameters of the proces of clot formation, its stabilization, and lysis. However, only one synthesized compound at concentration 10-fold higher than potential plasma concentrations contributed to the increase of general parameters such as the overall potential of clot formation and lysis (↑CLAUC and total time of the process (↑T. Results of described studies provide additional insight into delivery properties of PAMAM dendrimers but simultaneously underscore the necessity for further research.

  3. Characterization of complexes formed by polypropylene imine dendrimers and anti-HIV oligonucleotides.

    Science.gov (United States)

    Pedziwiatr-Werbicka, Elzbieta; Ferenc, Malgorzata; Zaborski, Marian; Gabara, Barbara; Klajnert, Barbara; Bryszewska, Maria

    2011-04-01

    Current anti-HIV therapies are capable of controlling viral infection but do not represent a definitive cure. They rely on the administration of antiretroviral nucleoside analogues, either alone or in combination with vectors. Dendrimers are branched, synthetic polymers with layered architectures, promising non-viral vectors in gene therapy. The aim of the paper was to study the interactions between three anti-HIV antisense oligonucleotides (ODNs): SREV, ANTI TAR, GEM91 and different generation polypropylene imine dendrimers (PPI) by monitoring changes in the fluorescence polarization of fluorescein attached to the ends of the ODNs when increasing concentrations of dendrimers were added. Laser Doppler electrophoresis, dynamic light scattering (DLS) and transmission electron microscopy (TEM) were used to characterize, respectively, zeta potential, particle size and morphology of dendriplexes formed in different molar ratios. Antisense oligonucleotides interacted with polypropylene imine dendrimers in different molar ratios depending on generation. Zeta potential of dendriplexes varied from (-25 to -21) mV to -5 mV (for PPIG3 and PPIG4 complexes) and to zero (for PPIG2 complexes). The structures presented a polydisperse size from about 50 nm to even 700-800 nm by TEM and about 250 nm by DLS. It means that besides single dendriplexes, aggregates were also present. Copyright © 2010 Elsevier B.V. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-03-15

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

  5. 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 (Gn-PEG-Gn) 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 G3-PEG-G3 (G3-PEG-G3/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.

  6. Electrochemical aptasensor of cellular prion protein based on modified polypyrrole with redox dendrimers.

    Science.gov (United States)

    Miodek, A; Castillo, G; Hianik, T; Korri-Youssoufi, H

    2014-06-15

    This work consists of the development of an electrochemical aptasensor based on polyprrole modified with redox dendrimers, able to detect human cellular prions PrP(C) with high sensitivity. The gold surface was modified by conductive polypyrrole film coupled to polyamidoamine dendrimers of fourth generation (PAMAM G4) and ferrocenyl group as redox marker. The aptamers were immobilized on the surface via biotin/streptavidin chemistry. Electrochemical signal was detected by ferrocenyl group incorporated between dendrimers and aptamers layers. We demonstrated that the interaction between aptamer and prion protein led to variation in electrochemical signal of the ferrocenyl group. The kinetics parameters (diffusion coefficient D and heterogeneous constant transfer ket) calculated from electrochemical signals demonstrate that the variation in redox signal results from the lower diffusion process of ions during redox reaction after prion interaction due to bulk effect of larger protein. The association of redox dendrimers with conducting polypyrrole leads to high sensitivity of PrP(C) determination with detection limit of 0.8 pM, which is three orders of magnitude lower, compared to flat ferrocene-functionalized polypyrrole. Detection of PrP(C) in spiked blood plasma has been achieved and demonstrated a recovery up to 90%. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Optical coherence tomography to delineate the interactions of PAMAM dendrimers with the porcine skin surface

    Science.gov (United States)

    Judd, Amy M.; Moss, Gary P.; Heylings, Jon; Wan, Ka-Wai; Yang, Ying

    2013-02-01

    Polyamidoamine (PAMAM) dendrimers have been topically applied to the skin and utilised as a permeation enhancer for a range of therapeutic compounds. However, very little is known about the mechanism of enhancement. This study used optical coherence tomography (OCT) to investigate the influence of PAMAM dendrimers to alter surface refractive index (RI) in excised porcine skin. It is revealed that PAMAM dendrimers caused a sporadic disruption and disappearance of the white hyper-reflective band on the skin surface using OCT. Following the decontamination of the treated skin specimens, the entrance signal, resulting in the polarised light reflecting off the keratin of the upper skin strata, returned to normal. Further, PAMAM-induced changes in skin RI was benchmarked against glycerol, a known permeation enhancer and skin clearing agent. Changes in RI with PAMAM were only observed on the skin surface, suggesting that the dendrimer only modulates the outer layers of the stratum corneum. This is substantially different to the observed effect of glycerol, which permeated more deeply into the skin. The non-invasive and non-destructive OCT imaging technique may provide a convenient tool to investigate the mechanism of permeation enhancement and transdermal drug delivery.

  8. AS1411 Aptamer-Anionic Linear Globular Dendrimer G2-Iohexol Selective Nano-Theranostics.

    Science.gov (United States)

    Mohammadzadeh, Pardis; Cohan, Reza Ahangari; Ghoreishi, Seyedeh Masoumeh; Bitarafan-Rajabi, Ahmad; Ardestani, Mehdi Shafiee

    2017-09-19

    Molecular theranostics is of the utmost interest for diagnosis as well as treatment of different malignancies. In the present study, anionic linear globular dendrimer G2 is employed as a suitable carrier for delivery and AS1411 aptamer is exploited as the targeting agent to carry Iohexol specifically to the human breast cancer cells (MCF-7). Dendrimer G2 was prepared and conjugation of dendrimer and aptamer was carried out thereafter. Based on the data yielded by AFM, morphology of smooth and spherical non-targeted dendrimer changed to the rough aspherical shape when it conjugated. Then, conjugation was confirmed using DLS, ELS and SLS methods. Toxicity on nucleolin positive MCF-7 cells and nucleolin negative HEK-293 cells was assessed by XTT and apoptosis/necrosis assays. In vitro uptake was determined using DAPI-FITC staining and ICP-MS methods. In vivo studies including in vivo CT imaging, pathology and blood tests were done to confirm the imaging ability, bio-safety and targeted nature of the Nano-Theranostics in vivo. In a nutshell, the prepared construction showed promising effects upon decreasing the toxicity of Iohexol on normal cells and accumulation of it in the cancer tumors as well as reducing the number of cancer cells.

  9. Enhancement of Muramyldipeptide (MDP) Immunostimulatory Activity by Controlled Multimerization on Dendrimers

    DEFF Research Database (Denmark)

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

    2011-01-01

    Peptidoglycan is a widespread bacterial PAMP molecule and a powerful initiator of innate immune responses. It consists of repeating units of MDP, which as a monomer is only weakly immunostimulatory. Here, MDP-coupled dendrimers were prepared and investigated for stimulation of pig blood mononuclear...

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

    Directory of Open Access Journals (Sweden)

    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

  11. Poly(Amido Amine) Dendrimers as Absorption Enhancers for Oral Delivery of Camptothecin

    Science.gov (United States)

    Sadekar, S.; Thiagarajan, G.; Bartlett, K.; Hubbard, D.; Ray, A.; McGill, L.D.; Ghandehari, H.

    2014-01-01

    Oral delivery of camptothecin has a treatment advantage but is limited by low bioavailability and gastrointestinal toxicity. Poly(amido amine) or PAMAM dendrimers have shown promise as intestinal penetration enhancers, drug solubilizers and drug carriers for oral delivery in vitro and in situ. There have been very limited studies in vivo to evaluate PAMAM dendrimers for oral drug delivery. In this study, camptothecin (5 mg/kg) was formulated and co-delivered with cationic, amine-terminated PAMAM dendrimer generation 4.0 (G4.0) (100 and 300 mg/kg) and anionic, carboxylate-terminated PAMAM generation 3.5 (G3.5) (300 and 1000 mg/kg) in CD-1 mice. Camptothecin associated to a higher extent with G4.0 than G3.5 in the formulation, attributed to an electrostatic interaction on the surface of G4.0. Both PAMAM G4.0 and G3.5 increased camptothecin solubilization in simulated gastric fluid and caused a 2-3 fold increase in oral absorption of camptothecin when delivered at 2 hours. PAMAM G4.0 and G3.5 did not increase mannitol transport suggesting that the oral absorption of camptothecin was not due to tight junction modulation. Histologic observations of the epithelial layer of small intestinal segments of the gastrointestinal tract (GIT) at 4 hours post dosing supported no evidence of toxicity at the evaluated doses of PAMAM dendrimers. This study demonstrates that both cationic (G.4) and anionic (G3.5) PAMAM dendrimers were effective in enhancing the oral absorption of camptothecin. Results suggest that drug inclusion in PAMAM interior controlled solubilization in simulated gastric and intestinal fluids, and increased oral bioavailability. PMID:23933439

  12. 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.

  13. Polycationic antimicrobial dendrimers: a comparison of alkyl pyridinium,quaternary ammonium, quaternary phosphonium and tertiary sulfonium salts

    Science.gov (United States)

    Chen, Chris; Cooper, Stuart

    2000-03-01

    Polycationic biocides usually kill bacteria through the interactions of the positively charged head groups with negatively charged bacteria and the interactions of the hydrophobic segments with phospholipid cell membranes, which implies that high local charge densities and a large number of hydrophobic groups would lead to enhanced biocidal potency. The advent of dendrimers offers us the first-ever opportunity to achieve the desired high local density. We have demonstrated that dimethyl dodecyl ammonium chloride functionalized polypropylene imine dendrimers are over 100 times more potent than their small molecule ounterparts. In this study, quaternary ammonium, quaternary phosphonium, alkyl pyridinium and tertiary sulfonium salts based on polypropylene imine dendrimers have been synthesized and characterized. Their antimicrobial properties have been quantified with a novel bioluminescence method. The structure-activity relationship of these polycationic dendrimers has also been investigated to elucidate the molecular mechanism for the enhanced antimicrobial effects.

  14. In vitro and in vivo uptake studies of PAMAM G4.5 dendrimers in breast cancer.

    Science.gov (United States)

    Oddone, Natalia; Lecot, Nicole; Fernández, Marcelo; Rodriguez-Haralambides, Alejandra; Cabral, Pablo; Cerecetto, Hugo; Benech, Juan Claudio

    2016-06-13

    Breast cancer is the second leading cause of cancer death worldwide. Nanotechnology approaches can overcome the side effects of chemotherapy as well as improve the efficacy of drugs. Dendrimers are nanometric size polymers which are suitable as drug delivery systems. To the best of our knowledge, studies on the application of PAMAM G4.5 (polyamidoamine half generation 4) dendrimers as potential drug delivery systems in breast cancer have not been reported. In this work we developed a PAMAM G4.5 dendrimer containing FITC (fluorescein isothiocyanate) dye to study their uptake by murine breast cancer cells and BALB/c mice breast tumors. We performed a reaction between FITC and PAMAM G4.5 dendrimers which were previously derivatized with piperazine (linker molecule), characterized them by (1)H NMR (proton nuclear magnetic resonance) spectroscopy and MALDI-TOF (matrix-assisted laser desorption/ionization- time-of-flight) mass spectrometry. The experimental data indicated that 2 FITC molecules could be bound covalently at the PAMAM G4.5 dendrimer surface, with 17 FITC molecules probably occluded in PAMAM dendrimers cavity. PAMAM-FITC dendrimer (PAMAM G4.5-piperazinyl-FITC dendrimer) size distribution was evaluated by DLS (dynamic light scattering) and TEM (transmission electron microscopy). The nanoparticle hydrodynamic size was 96.3 ± 1.4 nm with a PdI (polydispersion index) of 0.0296 ± 0.0171, and the size distribution measured by TEM was 44.2 ± 9.2 nm. PAMAM-FITC dendrimers were neither cytotoxic in 4T1 cells nor hemolytic up to 24 h of incubation. In addition, they were uptaken in vitro by 4T1 cells and in vivo by BALB/c mice breast tumors. PAMAM G4.5-piperazinyl-FITC dendrimer intracellular distribution was observed through histologic analysis of the tumor by laser confocal microscopy. These results indicate that PAMAM G4.5 dendrimers enter tumor tissue cells, being good candidates to be used as antitumor drug delivery systems for breast cancer treatment

  15. Functionally layered dendrimers: a new building block and its application to the synthesis of multichromophoric light-harvesting systems.

    Science.gov (United States)

    Dichtel, William R; Hecht, Stefan; Fréchet, Jean M J

    2005-09-29

    [reaction: see text] A divergent synthesis of internally functionalized dendrimers based on a modular functional monomer has been developed. This strategy was applied to the construction of a light-harvesting dendrimer containing one set of naphthopyranone dyes located at the interior and another set of coumarin chromophores located in the adjacent outer layer surrounding a porphyrin acceptor. Quantitative energy transfer from both donor pigments is observed, giving rise to exclusive emission from the porphyrin core over all excitation wavelengths.

  16. Self-assembly of amphiphilic Janus dendrimers into uniform onion-like dendrimersomes with predictable size and number of bilayers

    OpenAIRE

    Zhang, Shaodong; Sun, Hao-Jan; Hughes, Andrew D.; Moussodia, Ralph-Olivier; Bertin, Annabelle; Chen, Yingchao; Pochan, Darrin J.; Heiney, Paul A.; Klein, Michael L.; Percec, Virgil

    2014-01-01

    Simple injection of a solution of amphiphilic Janus dendrimer with specific primary structure into water or buffer has been shown to yield uniform submicrometer-size onion-like vesicles denoted dendrimersomes. The size and number of alternating internally confined bilayers is predicted by the final concentration of the Janus dendrimer. Onion-like dendrimersomes provide mimics of various biological membranes and can be elaborated to provide time-dependent delivery of drugs. Their ease of prepa...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Pople, John A

    2001-03-22

    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) < 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.

  19. Near Edge X-ray Absorption Fine Structure Studies of Cu Ion-Containing PAMAMOS Dendrimer Networks

    Science.gov (United States)

    Bubeck, Robert; Dvornic, Petar; Fischer, Daniel

    2012-02-01

    There is continuing interest in the development of nanocomposites containing metal ions based on the use of dendrimers as the host matrix. One may utilize functionalized dendrimer interiors to complex the added constituent and serve as a template for the organization of the resulting nanoscale structures. Potential applications of include: catalysts, biotechnology, functional membranes, molecular sensors, etc. We report on recent results obtained using near edge X-ray absorption fine structure (NEXAFS) to characterize Cu(2+) covalent interactions in three-dimensionally cross linked dendrimer networks. These networks were made from radially-layered poly(amidoamine-organosilicon), PAMAMOS, dendrimers having generation 4 (G4) polyamidoamine (PAMAM) interiors surrounded by one layer of organosilicon, OS, exterior branch cells. Lower generation homologues (i.e., G1 through G3) were also examined on a more limited basis. The nitrogen and carbonyl moieties contained in the PAMAM dendrimer interior were shown to be highly interactive with metallic cations, in large measure because of the dendrimer geometry. Similar measurements on chemically similar but much less physically constraining hyperbranched polymers indicated very limited interaction with the amine and carbonyl moieties.

  20. New Ionic bis-MPA and PAMAM Dendrimers: A Study of Their Biocompatibility and DNA-Complexation.

    Science.gov (United States)

    Movellan, Julie; González-Pastor, Rebeca; Martín-Duque, Pilar; Sierra, Teresa; de la Fuente, Jesús M; Serrano, José Luis

    2015-05-01

    Herein, the synthesis of five novel ionic dendrimers and their evaluation as biological carriers is reported. The compounds include an ionic bis-MPA dendrimer and four PAMAM dendrimers of different generations decorated with negatively charged hydrophilic chains of 2-[2-(2-methoxyethoxy)ethoxy]acetic acid as counter ions in order to increase their biocompatibility. The ionic dendrimers derived from bis-MPA have a low cytotoxicity at 0.5 mg · mL(-1) against U251MG and are even less toxic against mesenchymal stem cells; however, the PAMAM derivatives show high cytotoxicity at the same concentration. The five compounds are able to form complexes with plasmid DNA at different N/P ratios. The cytotoxicity and complexation ability of the new dendrimers were also compared with jetPEI, a linear polyethylenimine derivative commercially available as transfection reagent. The results indicate that the cytotoxicity of the ionic PAMAM dendrimers remains as an important drawback, whereas the ionic I-bis-MPA compound exhibits a high ability to complex pDNA and very low toxicity compared with jetPEI. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Studies towards biocompatibility of PAMAM dendrimers--overall hemostasis potential and integrity of the human aortic endothelial barrier.

    Science.gov (United States)

    Markowicz-Piasecka, Magdalena; Łuczak, Emilia; Chałubiński, Maciej; Broncel, Marlena; Mikiciuk-Olasik, Elżbieta; Sikora, Joanna

    2014-10-01

    The last decade has brought many examples of utilization of dendrimers as drug delivery systems; however, their possible application is limited because of inherent toxicity associated with them. This study discusses the influence of G1-G4 PAMAM-NH2 dendrimers on the process of hemostasis and integrity of endothelial monolayer. The global assay of coagulation and fibrinolysis was investigated spectrophotometrically by means of CL-test at 405 nm. Thrombin (0.5 I U/mL) and t-PA (240 ng/mL) were used to obtain clotting and lysis curve. The activity of thrombin was determined by means of chromogenic substrate S-2238. The influence of PAMAM dendrimers on the barrier properties of human primary aortal endothelium was assessed by means of method based on the measurements of the impedance changes of the cells. Observed multidirectional impact of dendrimers, without affecting the thrombin activity, on clot formation, its stabilization and fibrinolysis could be regarded as important when trying to use them clinically. It is crucial that examined PAMAM dendrimers did not lead to spontaneous aggregation of fibrinogen. Importantly, examined polymers have concentration- and generation-dependent adverse effect towards the endothelial monolayer. of described studies provide additional insight into PAMAM dendrimers toxicity associated with systemic administration and underscore the necessity for further research. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Effective targeting of gemcitabine to pancreatic cancer through PEG-cored Flt-1 antibody-conjugated dendrimers.

    Science.gov (United States)

    Öztürk, Kıvılcım; Esendağlı, Güneş; Gürbüz, Mustafa Ulvi; Tülü, Metin; Çalış, Sema

    2017-01-30

    Tumor-targeted delivery of anticancer drugs using dendrimers has been recognized as a promising strategy to increase efficiency and reduce adverse effects of chemotherapy. Herein, we developed a dendrimer-based drug delivery system targeting Flt-1 (a receptor for vascular endothelial growth factors (VEGF)) receptor to improve therapeutic efficacy of gemcitabine in pancreatic cancer. Synthesized polyethylene glycol (PEG)-cored PAMAM dendrimers, which bear anionic carboxylic acid groups on the surface were modified with PEG chains, which were then conjugated with Flt-1 antibody. Following structural and chemical characterization studies, gemcitabine HCl-dendrimer inclusion complexes were successfully prepared. These complexes were efficiently engulfed by Flt-1 expressing pancreatic cancer cells, which enhanced the cytotoxicity of gemcitabine. Moreover, pancreatic tumors established in mice were highly targeted by PEG-cored Flt-1 antibody-conjugated dendrimers and increased accumulation of these gemcitabine-loaded complexes exhibited satisfactory in vivo anti-cancer efficacy. In conclusion, dendrimer-based targeted delivery of chemotherapeutics may serve as a promising approach for the treatment of malignancies such as pancreatic cancer that do not benefit from conventional chemotherapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Anti-Microbial Dendrimers against Multidrug-Resistant P. aeruginosa Enhance the Angiogenic Effect of Biological Burn-wound Bandages.

    Science.gov (United States)

    Abdel-Sayed, Philippe; Kaeppeli, Ariane; Kaeppli, Ariane; Siriwardena, Thissa; Darbre, Tamis; Perron, Karl; Jafari, Paris; Reymond, Jean-Louis; Pioletti, Dominique P; Applegate, Lee Ann

    2016-02-25

    Multi-drug resistant Pseudomonas aeruginosa has increased progressively and impedes further regression in mortality in burn patients. Such wound infections serve as bacterial reservoir for nosocomial infections and are associated with significant morbidity and costs. Anti-microbial polycationic dendrimers G3KL and G3RL, able to kill multi-drug resistant P. aeruginosa, have been previously developed. The combination of these dendrimers with a class of biological bandages made of progenitor skin cells, which secrete growth factors, could positively impact wound-healing processes. However, polycations are known to be used as anti-angiogenic agents for tumor suppression. Since, neovascularization is pivotal in the healing of deep burn-wounds, the use of anti-microbial dendrimers may thus hinder the healing processes. Surprisingly, we have seen in this study that G3KL and G3RL dendrimers can have angiogenic effects. Moreover, we have shown that a dendrimer concentration ranging between 50 and 100 μg/mL in combination with the biological bandages can suppress bacterial growth without altering cell viability up to 5 days. These results show that antimicrobial dendrimers can be used in combination with biological bandages and could potentially improve the healing process with an enhanced angiogenesis.

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

    Science.gov (United States)

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

    2015-11-01

    Four generations of poly(amidoamine) (PAMAM) dendrimers incorporating benzenesulfonamide moieties were investigated as inhibitors of carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the α-, β-, γ- and η-classes which are present in pathogenic bacteria, fungi or protozoa. The following bacterial, fungal and protozoan organisms were included in the study: Vibrio cholerae, Trypanosoma cruzi, Leishmania donovani chagasi, Porphyromonas gingivalis, Cryptococcus neoformans, Candida glabrata, and Plasmodium falciparum. The eight pathozymes present in these organisms were efficiently inhibited by the four generations PAMAM-sulfonamide dendrimers, but multivalency effects were highly variable among the different enzyme classes. The Vibrio enzyme VchCA was best inhibited by the G3 dendrimer incorporating 32 sulfamoyl moieties. The Trypanosoma enzyme TcCA on the other hand was best inhibited by the first generation dendrimer G0 (with 4 sulfamoyl groups), whereas for other enzymes the optimal inhibitory power was observed for the G1 or G2 dendrimers, with 8 and 16 sulfonamide functionalities. This study thus proves that the multivalency may be highly relevant for enzyme inhibition for some but not all CAs from pathogenic organisms. On the other hand, some dendrimers investigated here showed a better inhibitory power compared to acetazolamide for enzymes from widespread pathogens, such as the η-CA from Plasmodium falciparum. Overall, the main conclusion is that this class of molecules may lead to important developments in the field of anti-infective CA inhibitors. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Paul D. Hamilton

    2009-08-01

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

  6. In vitro gene delivery using polyamidoamine dendrimers with a trimesyl core.

    Science.gov (United States)

    Zhang, Xue-Qing; Wang, Xu-Li; Huang, Shi-Wen; Zhuo, Ren-Xi; Liu, Zhi-Lan; Mao, Hai-Quan; Leong, Kam W

    2005-01-01

    Polyamidoamine (PAMAM) dendrimer represents one of the most efficient polymeric gene carriers. To investigate the effect of the core structure and generation of dendrimers on the complex formation and transfection efficiency, a series of PAMAM dendrimers with a trimesyl core (DT) at different generations (DT4 to DT8) were developed as gene carriers and compared with the PAMAM dendrimers derived from pentaerythritol (DP) and inositol (DI). The minimal generation number of DTs at which the dendrimer has enough amino group density to effectively condense DNA was higher (generation 6) than those of DPs and DIs (generation 5). DTs of generation 6 or higher condensed DNA into complexes with an average diameter ranging from 100 to 300 nm, but the 4th and 5th generations of DT (DT4 and DT5) formed only a severe aggregate with DNA. Interestingly, the DT6/pDNA complex was determined to be much smaller (100-300 nm) than those prepared with DP5 or DI5 (>600 nm) at N/P ratios higher than 15. The optimal generation numbers at which the dendrimers showed the highest transgene expression in COS-7 cells were 5 for DPs and DIs but 6 for DTs. The DT6/pDNAcomplex with smaller size mediated higher transgene expression in COS-7 cells than those prepared with DP5 or DI5. The in vitro transfection efficiency of the DT dendrimers as evaluated in HeLa cells, COS-7 cells, and primary hepatocytes decreased in the order of DT6 > DT7 > DT8 > DT5 > DT4. The transfection mediated by DT6 was significantly inhibited by bafilomycin A1. The acid-base titration curve for DT6 showed high buffer capacity in the pH range from 5.5 to 6.4 (pK(a) approximately 6). This permits dendrimers to buffer the pH change in the endosomal compartment. However, the transfection efficiency mediated by DT6 decreased significantly in the presence of serum in both HeLa cells and COS-7 cells. The cytotoxicity of DTs evaluated in HeLa cells using the 3-{4,5-dimethylthiazol-2-yl}-2,5-diphenyltetrazolium bromide assay showed a

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-11-15

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

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

    Science.gov (United States)

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

    2017-06-05

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

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

    Science.gov (United States)

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

    2014-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Eduard Karakhanov

    2017-03-01

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

  11. Vesicles from Amphiphilic Dumbbells and Janus Dendrimers: Bioinspired Self-Assembled Structures for Biomedical Applications

    Directory of Open Access Journals (Sweden)

    Soraya Taabache

    2017-07-01

    Full Text Available The current review focuses on vesicles obtained from the self-assembly of two types of dendritic macromolecules, namely amphiphilic Janus dendrimers (forming dendrimersomes and amphiphilic dumbbells. In the first part, we will present some synthetic strategies and the various building blocks that can be used to obtain dendritic-based macromolecules, thereby showing their structural versatility. We put our focus on amphiphilic Janus dendrimers and amphiphilic dumbbells that form vesicles in water but we also encompass vesicles formed thereof in organic solvents. The second part of this review deals with the production methods of these vesicles at the nanoscale but also at the microscale. Furthermore, the influence of various parameters (intrinsic to the amphiphilic JD and extrinsic—from the environment on the type of vesicle formed will be discussed. In the third part, we will review the numerous biomedical applications of these vesicles of nano- or micron-size.

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

    Directory of Open Access Journals (Sweden)

    Tomasz Borkowski

    2011-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-09-15

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Zeng Xin; Pan Shirong; Wang Chi; Wen Yuting; Wu Hongmei; Wang Cuifeng; Wu Chuanbin; Feng Min [School of Pharmaceutical Sciences and the First Affiliated Hospital, Sun Yat-sen University, 80 Zhongshan Road II, Guangzhou 510080 (China); Li Jie, E-mail: gzpshr@163.com, E-mail: fengmin@mail.sysu.edu.cn [Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-sen University, 80 Zhongshan Road II, Guangzhou 510080 (China)

    2011-09-16

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

  15. Design and studies of multiple mechanism of anti-Candida activity of a new potent Trp-rich peptide dendrimers.

    Science.gov (United States)

    Zielińska, Paulina; Staniszewska, Monika; Bondaryk, Małgorzata; Koronkiewicz, Mirosława; Urbańczyk-Lipkowska, Zofia

    2015-11-13

    Eight peptide dendrimers were designed as structural mimics of natural cationic amphiphilic peptides with antifungal activity and evaluated for their anti-Candida potential against the wild type strains and mutants. Dendrimer 14 containing four Trp residues and dodecyl tail and a slightly smaller dendrimer 9 decorated with four N-methylated Trp that displayed 100 and 99.7% of growth inhibition at 16 μg/mL respectively, were selected for evaluation against the Candida albicans mutants with disabled biosynthesis of aspartic proteases responsible for host tissue colonization and morphogenesis during biofilm formation (sessile model). Flow cytometry method was employed to detect apoptotic cells with membrane alterations (phosphatidylserine translocation), and differentiation of apoptotic from necrotic cells was also performed. Simultaneous staining of cell surface phosphatidylserine with Annexin-V-Fluorescein and necrotic cells with propidium iodide was conducted. 14 at 16 μg/mL caused C. albicans cells to undergo cellular apoptosis but its increasing concentrations induced necrosis. 14 influenced C. albicans biofilm viability as well as hyphal and cell wall morphology. Confocal microscopy and cell wall staining with calcofluor white revealed that in epithelial model the cell surface structure was perturbed at MIC of peptide dendrimer. It appears that tryptophan or 1-methyltryptophan groups displayed at the surface and positive charges hidden in the dendrimer tree along with hydrocarbon tail located at C-terminus are important for the anti-Candida activity since dendrimers containing tryptamine at C-terminus showed only a moderate activity. Our results suggest that membranolytic dendrimer 14, targeting cellular apoptotic pathway and impairing the cell wall formation in mature biofilm, may be a potential multifunctional antifungal lead compound for the control of C. albicans infections. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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

    Science.gov (United States)

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

    2011-09-01

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

  17. 8-Hydroxyquinoline Dansylates Modified with PAMAM Dendrimer as Fluorescent Fe3+ Sensors

    Directory of Open Access Journals (Sweden)

    Yaowu Sha

    2010-04-01

    Full Text Available A series of fluorescent sensors based on 8-hydroxyquinoline dansylate as core and dendritic PAMAM as shell were synthesized. Their fluorescence characteristic and fluorescent sensing behavior toward metal ions were studied in water/methanol (1: 1, v/v. The sensors exhibit good selectivity and sensitivity for Fe3+ ion and to some extent for Cr3+ ion. The third generation dendrimer has the better sensitivity than the first and second generations.

  18. 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

  19. Nanoparticle-cored dendrimers: functional hybrid nanocomposites as a new platform for drug delivery systems

    OpenAIRE

    Brunetti, Veronica; Bouchet, Lydia María; Strumia, Miriam Cristina

    2017-01-01

    Nanoparticle-cored dendrimers (NCDs) are now offering themselves as versatile carriers because of their colloidal stability, tunable membrane properties and ability to encapsulate or integrate a broad range of drugs and molecules. This kind of hybrid nanocomposite aims to combine the advantages of stimuliresponsive dendritic coatings, in order to regulate the drug release behaviour under different conditions and improve the biocompatibility and in vivo half-time circulation of the inorgan...

  20. Targeted cancer theranostics using alpha-tocopheryl succinate-conjugated multifunctional dendrimer-entrapped gold nanoparticles.

    Science.gov (United States)

    Zhu, Jingyi; Zheng, Linfeng; Wen, Shihui; Tang, Yueqin; Shen, Mingwu; Zhang, Guixiang; Shi, Xiangyang

    2014-08-01

    Development of multifunctional theranostic nanoplatforms for targeted cancer imaging and therapy still remains a great challenge. Herein, we report the use of multifunctional dendrimer-entrapped gold nanoparticles (Au DENPs) covalently linked with α-tocopheryl succinate (α-TOS) as a platform for targeted cancer computed tomography (CT) imaging and therapy. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 (G5.NH2) conjugated with fluorescein isothiocyanate (FI), polyethylene glycol (PEG)-modified α-TOS, and PEGylated folic acid (FA) were used as templates to synthesize Au DENPs, followed by acetylation of the remaining dendrimer terminal amines. The formed multifunctional Au DENPs were characterized via different techniques. We show that the Au DENPs conjugated with approximately 9.8 α-TOS molecules per dendrimer and with an Au core size of 3.3 nm are water-dispersible, and stable under different pH and temperature conditions and in different aqueous media. The FA modification onto the Au DENPs enables efficient targeting of the particles to cancer cells overexpressing FA receptors (FAR), and effective targeted CT imaging of the cancer cells in vitro and the xenografted tumor model in vivo. Likewise, the covalent conjugation of α-TOS does not compromise its therapeutic activity, instead significantly improves its water solubility. Importantly, thanks to the role of FA-directed targeting, the formed multifunctional Au DENPs are able to exert the specific therapeutic efficacy of α-TOS to the FAR-overexpressing cancer cells in vitro and the xenografted tumor model in vivo. The developed multifunctional Au DENPs may hold a great promise to be used as a unique theranostic nanoplatform for targeted CT imaging and therapy of different types of cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. COMPARATIVE PHARMACOKINETICS OF PAMAM-OH DENDRIMERS AND HPMA COPOLYMERS IN OVARIAN-TUMOR-BEARING MICE

    OpenAIRE

    Sadekar, S.; Linares, O.; Noh, GJ.; Hubbard, D; Ray, A.; Janát-Amsbury, M.; Peterson, C. M.; Facelli, J.; Ghandehari, H.

    2012-01-01

    The purpose of this study was to model data from a head to head comparison of the in vivo fate of hyper-branched PAMAM dendrimers with linear HPMA copolymers in order to understand the influence of molecular weight (MW), hydrodynamic size (Rh) and polymer architecture on biodistribution in tumor-bearing mice using compartmental pharmacokinetic analysis. Plasma concentration data was modeled by two-compartment analysis using Winnonlin® to obtain elimination clearance (E.CL) and plasma exposure...

  2. 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.

  3. Efficient electrocatalytic oxidation of formic acid using Au@Pt dendrimer-encapsulated nanoparticles.

    Science.gov (United States)

    Iyyamperumal, Ravikumar; Zhang, Liang; Henkelman, Graeme; Crooks, Richard M

    2013-04-17

    We report electrocatalytic oxidation of formic acid using monometallic and bimetallic dendrimer-encapsulated nanoparticles (DENs). The results indicate that the Au147@Pt DENs exhibit better electrocatalytic activity and low CO formation. Theoretical calculations attribute the observed activity to the deformation of nanoparticle structure, slow dehydration of formic acid, and weak binding of CO on Au147@Pt surface. Subsequent experiments confirmed the theoretical predictions.

  4. 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.

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

    Science.gov (United States)

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

    2015-04-01

    This paper describes a novel strategy for targeted delivery of amphotericin B (AmB) to macrophages with muramyl dipeptide (MDP) conjugated multimeric poly(propyleneimine) (PPI) dendrimers. Synergistic antiparasitic activity due to immunostimulation by multimeric presentation of MDP on dendrimers was anticipated. MDP conjugated 5.0G PPI (MdPPI) dendrimers were synthesized and characterized. Therapeutic activity and toxicity of dendrimeric formulation of AmB (MdPPIA) were compared with marketed formulations of AmB. Highly significant (P<0.01) reduction in toxicity was observed in hemolytic toxicity and cytotoxicity studies in erythrocytes and J774A.1 macrophage cells, respectively. Formulation MdPPIA showed appreciable macrophage targeting potential and higher or equivalent antiparasitic activity against parasite infected macrophage cell lines and in vivo infection in Balb/c mice. These results suggest the developed MDP conjugated dendrimeric formulation of AmB as a promising immunostimulant targeted drug delivery system and a safer alternative to marketed formulations. From the clinical editor: Parasitic infections remain a significant issue in the clinical setting. The authors in this article studied the use of ligand anchored dendrimeric formulation of Amphotericin B to target infected macrophages and showed reduced toxicity, high anti-leishmanial activity. This may add another treatment option to available formulations in the future. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Self-assembly of amphiphilic Janus dendrimers into mechanically robust supramolecular hydrogels for sustained drug release.

    Science.gov (United States)

    Nummelin, Sami; Liljeström, Ville; Saarikoski, Eve; Ropponen, Jarmo; Nykänen, Antti; Linko, Veikko; Seppälä, Jukka; Hirvonen, Jouni; Ikkala, Olli; Bimbo, Luis M; Kostiainen, Mauri A

    2015-10-05

    Compounds that can gelate aqueous solutions offer an intriguing toolbox to create functional hydrogel materials for biomedical applications. Amphiphilic Janus dendrimers with low molecular weights can readily form self-assembled fibers at very low mass proportion (0.2 wt %) to create supramolecular hydrogels (G'≫G'') with outstanding mechanical properties and storage modulus of G'>1000 Pa. The G' value and gel melting temperature can be tuned by modulating the position or number of hydrophobic alkyl chains in the dendrimer structure; thus enabling exquisite control over the mesoscale material properties in these molecular assemblies. The gels are formed within seconds by simple injection of ethanol-solvated dendrimers into an aqueous solution. Cryogenic TEM, small-angle X-ray scattering, and SEM were used to confirm the fibrous structure morphology of the gels. Furthermore, the gels can be efficiently loaded with different bioactive cargo, such as active enzymes, peptides, or small-molecule drugs, to be used for sustained release in drug delivery. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Construction of novel electrochemical immunosensor for detection of prostate specific antigen using ferrocene-PAMAM dendrimers.

    Science.gov (United States)

    Çevik, Emre; Bahar, Özlem; Şenel, Mehmet; Abasıyanık, M Fatih

    2016-12-15

    In this study, an immunosensor was designed to utilize for the detection of prostate specific antigen (PSA) based on three different generations (G1, G2 and G3) of ferrocene (Fc) cored polyamidiamine dendrimers (Fc-PAMAM) gold (Au) electrode. The self-assembled monolayer principle (SAM) was used to fabricate the sensitive, selective and disposable immunosensor electrodes. In electrode fabrication cysteamine (Cys) was the first agent covalently linked on the Au electrode surface. Immobilized redox center (ferrocene) cored PAMAM dendrimers served as a layer for the further binding of biological components. The monoclonal antibody of PSA (anti-PSA) was covalently immobilized on dendrimers which were attached onto the modified Au surface (Au/Cys/Fc-PAMAMs/anti-PSA). PSA levels were quantitatively analyzed by using electrochemical differential pulse voltammetry (DPV) whose lowest detection limit was calculated as 0.001ngmL(-1). The Au/Cys/FcPAMAM/anti-PSA immunosensor showed excellent performance for PSA at the pulse amplitude; 50mV and the scan rate; 10mV/s in a wide linear concentration range of 0.01ng-100ngmL(-1). Analytical performance and specificity assays were carried out using human serum and different proteins. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. EGFR-Targeted Adenovirus Dendrimer Coating for Improved Systemic Delivery of the Theranostic NIS Gene

    Directory of Open Access Journals (Sweden)

    Geoffrey K Grünwald

    2013-01-01

    Full Text Available We recently demonstrated tumor-selective iodide uptake and therapeutic efficacy of combined radiovirotherapy after systemic delivery of the theranostic sodium iodide symporter (NIS gene using a dendrimer-coated adenovirus. To further improve shielding and targeting we physically coated replication-selective adenoviruses carrying the hNIS gene with a conjugate consisting of cationic poly(amidoamine (PAMAM dendrimer linked to the peptidic, epidermal growth factor receptor (EGFR-specific ligand GE11. In vitro experiments demonstrated coxsackie-adenovirus receptor-independent but EGFR-specific transduction efficiency. Systemic injection of the uncoated adenovirus in a liver cancer xenograft mouse model led to high levels of NIS expression in the liver due to hepatic sequestration, which were significantly reduced after coating as demonstrated by 123I-scintigraphy. Reduction of adenovirus liver pooling resulted in decreased hepatotoxicity and increased transduction efficiency in peripheral xenograft tumors. 124I-PET-imaging confirmed EGFR-specificity by significantly lower tumoral radioiodine accumulation after pretreatment with the EGFR-specific antibody cetuximab. A significantly enhanced oncolytic effect was observed following systemic application of dendrimer-coated adenovirus that was further increased by additional treatment with a therapeutic dose of 131I. These results demonstrate restricted virus tropism and tumor-selective retargeting after systemic application of coated, EGFR-targeted adenoviruses therefore representing a promising strategy for improved systemic adenoviral NIS gene therapy.

  9. EGFR-Targeted Adenovirus Dendrimer Coating for Improved Systemic Delivery of the Theranostic NIS Gene.

    Science.gov (United States)

    Grünwald, Geoffrey K; Vetter, Alexandra; Klutz, Kathrin; Willhauck, Michael J; Schwenk, Nathalie; Senekowitsch-Schmidtke, Reingard; Schwaiger, Markus; Zach, Christian; Wagner, Ernst; Göke, Burkhard; Holm, Per S; Ogris, Manfred; Spitzweg, Christine

    2013-11-05

    We recently demonstrated tumor-selective iodide uptake and therapeutic efficacy of combined radiovirotherapy after systemic delivery of the theranostic sodium iodide symporter (NIS) gene using a dendrimer-coated adenovirus. To further improve shielding and targeting we physically coated replication-selective adenoviruses carrying the hNIS gene with a conjugate consisting of cationic poly(amidoamine) (PAMAM) dendrimer linked to the peptidic, epidermal growth factor receptor (EGFR)-specific ligand GE11. In vitro experiments demonstrated coxsackie-adenovirus receptor-independent but EGFR-specific transduction efficiency. Systemic injection of the uncoated adenovirus in a liver cancer xenograft mouse model led to high levels of NIS expression in the liver due to hepatic sequestration, which were significantly reduced after coating as demonstrated by (123)I-scintigraphy. Reduction of adenovirus liver pooling resulted in decreased hepatotoxicity and increased transduction efficiency in peripheral xenograft tumors. (124)I-PET-imaging confirmed EGFR-specificity by significantly lower tumoral radioiodine accumulation after pretreatment with the EGFR-specific antibody cetuximab. A significantly enhanced oncolytic effect was observed following systemic application of dendrimer-coated adenovirus that was further increased by additional treatment with a therapeutic dose of (131)I. These results demonstrate restricted virus tropism and tumor-selective retargeting after systemic application of coated, EGFR-targeted adenoviruses therefore representing a promising strategy for improved systemic adenoviral NIS gene therapy.Molecular Therapy-Nucleic Acids (2013) 2, e131; doi:10.1038/mtna.2013.58; published online 5 November 2013.

  10. 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.

  11. Dendritic structure having a potential gradient: new synthesis and properties of carbazole dendrimers.

    Science.gov (United States)

    Albrecht, Ken; Yamamoto, Kimihisa

    2009-02-18

    A new synthetic route for carbazole dendrimers was discovered using the copper-catalyzed N-arylation reaction. This synthetic route allowed synthesizing the fourth generation carbazole dendrimer and several derivatives for the first time. The crystal structure, Mark-Houwink-Sakurada plots, and UV-vis and fluorescence studies showed that the dendritic carbazole backbone has a rigid and highly twisted structure. From the measurement of the redox potential of the ferrocene derivatives, the IR spectra of the benzophenone derivatives, and complexation behavior of the phenylazomethine derivatives, the inductive electron-withdrawing effect of the carbazole dendron was revealed. This suggested that the summation of this electron withdrawal from each layer may produce a potential gradient such that the outer layer is electron-rich and the inner layer is electron-poor in the carbazole dendron. By assignment of the (1)H and (13)C NMR spectra of the dendron, the existence of this kind of potential gradient was proved. Overall, these data show the pi-polarization substituent effect of the carbazole unit, and their summation determines the potential gradient in the repeating dendritic structure of the carbazole dendrimer.

  12. PAMAM Dendrimers Cross the Blood-Brain Barrier When Administered through the Carotid Artery in C57BL/6J Mice.

    Science.gov (United States)

    Srinageshwar, Bhairavi; Peruzzaro, Sarah; Andrews, Melissa; Johnson, Kayla; Hietpas, Allison; Clark, Brittany; McGuire, Crystal; Petersen, Eric; Kippe, Jordyn; Stewart, Andrew; Lossia, Olivia; Al-Gharaibeh, Abeer; Antcliff, Aaron; Culver, Rebecca; Swanson, Douglas; Dunbar, Gary; Sharma, Ajit; Rossignol, Julien

    2017-03-14

    Drug delivery into the central nervous system (CNS) is challenging due to the blood-brain barrier (BBB) and drug delivery into the brain overcoming the BBB can be achieved using nanoparticles such as dendrimers. The conventional cationic dendrimers used are highly toxic. Therefore, the present study investigates the role of novel mixed surface dendrimers, which have potentially less toxicity and can cross the BBB when administered through the carotid artery in mice. In vitro experiments investigated the uptake of amine dendrimers (G1-NH₂ and G4-NH₂) and novel dendrimers (G1-90/10 and G4-90/10) by primary cortical cultures. In vivo experiments involved transplantation of G4-90/10 into mice through (1) invasive intracranial injections into the striatum; and (2) less invasive carotid injections. The animals were sacrificed 24-h and 1-week post-transplantations and their brains were analyzed. In vivo experiments proved that the G4-90/10 can cross the BBB when injected through the carotid artery and localize within neurons and glial cells. The dendrimers were found to migrate through the corpus callosum 1-week post intracranial injection. Immunohistochemistry showed that the migrating cells are the dendrimer-infected glial cells. Overall, our results suggest that poly-amidoamine (PAMAM) dendrimers may be used as a minimally invasive means to deliver biomolecules for treating neurological diseases or disorders.

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  14. Topical gene silencing by iontophoretic delivery of an antisense oligonucleotide-dendrimer nanocomplex: the proof of concept in a skin cancer mouse model

    Science.gov (United States)

    Venuganti, , Venkata Vamsi K.; Saraswathy, Manju; Dwivedi, Chandradhar; Kaushik, Radhey S.; Perumal, Omathanu P.

    2015-02-01

    The study was aimed at investigating the feasibility of using a poly (amidoamine) (PAMAM) dendrimer as a carrier for topical iontophoretic delivery of an antisense oligonucleotide (ASO). Bcl-2, an anti-apoptotic protein implicated in skin cancer, was used as the model target protein to demonstrate the topical gene silencing approach. Confocal laser scanning microscopy studies demonstrated that the iontophoretically delivered ASO-dendrimer complex can reach the viable epidermis in porcine skin. In contrast, passively delivered free or dendrimer complexed ASO was mainly localized to the stratum corneum. The cell uptake of ASO was significantly enhanced by the dendrimer complex and the complex suppressed Bcl-2 levels in the cell. In the skin cancer mouse model, the iontophoretically delivered ASO-dendrimer complex reduced the tumor volume by 45% and was consistent with the reduction in Bcl-2 protein levels. The iontophoretically delivered ASO-dendrimer complex caused significant apoptosis in skin tumor. Overall, the findings from this study demonstrate that dendrimers are promising nanocarriers for developing topical gene silencing approaches for skin diseases.The study was aimed at investigating the feasibility of using a poly (amidoamine) (PAMAM) dendrimer as a carrier for topical iontophoretic delivery of an antisense oligonucleotide (ASO). Bcl-2, an anti-apoptotic protein implicated in skin cancer, was used as the model target protein to demonstrate the topical gene silencing approach. Confocal laser scanning microscopy studies demonstrated that the iontophoretically delivered ASO-dendrimer complex can reach the viable epidermis in porcine skin. In contrast, passively delivered free or dendrimer complexed ASO was mainly localized to the stratum corneum. The cell uptake of ASO was significantly enhanced by the dendrimer complex and the complex suppressed Bcl-2 levels in the cell. In the skin cancer mouse model, the iontophoretically delivered ASO-dendrimer complex

  15. Matrix-assisted resonant infrared pulsed laser ablation of electroluminescent dendrimers

    Science.gov (United States)

    Torres-Pagan, Ricardo Daniel

    The deposition techniques for polymer thin films in organic light emitting diodes are limited to wet methods since molecular pyrolysis prevents the use of dry vacuum thermal evaporation methods. Wet methods have critical limitations such as poor thickness control, drying patterns and re-dissolution of previous layers. In this work, a novel approach, Matrix-Assisted Resonant Infrared Pulsed Laser Ablation (RIM-PLA) has been studied as an alternative deposition method for electroluminescent polymer films. RIM-PLA was successfully used for the deposition of two model dendrimers: fluorescent and phosphorescent Ir-cored. A free-electron laser was tuned to resonance frequencies for the vibrational modes of two solid matrix solvents: chloroform (C-H stretch; C-H bending) and toluene (C-H stretch; C=C stretch). The temperature-dependent absorption coefficients for each resonance mode were measured. Targets made from flash-frozen, low-concentration solutions of the dendrimers were irradiated at each frequency while varying fluence and exposure times. The molecular structure integrity of the targets was characterized. The deposited films were characterized to assess structure fidelity, roughness and topography, and luminance. All RIM-PLA deposited films were compared with spin-coated films. The ablation characteristics for each mode were found to be dependent on the solvent and not the dendrimer. Calculations from a temperature-rise model show that FEL pulsed-irradiation results in heating rates on the order of 108--109 K/s, resulting in metastable condensed targets. Thermodynamic and kinetic relations were used to calculate the relevance of three ablation mechanisms: normal vaporization, normal boiling and phase explosion. The latter mechanism has a critical threshold (> 0.8 Tc) for each solvent, and proceeds through spinodal decay followed by rapid homogeneous nucleation of vapor bubbles within the focal volume. For both chloroform modes, the primary ablation mechanism was

  16. 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

  17. Triblock copolymers encapsulated poly (aryl benzyl ether) dendrimer zinc(II) phthalocyanine nanoparticles for enhancement in vitro photodynamic efficacy.

    Science.gov (United States)

    Huang, Yide; Yu, Huizhen; Lv, Huafei; Zhang, Hong; Ma, Dongdong; Yang, Hongqin; Xie, Shusen; Peng, Yiru

    2016-12-01

    A novel series of nanoparticles formed via an electrostatic interaction between the periphery of negatively charged 1-2 generation aryl benzyl ether dendrimer zinc (II) phthalocyanines and positively charged poly(L-lysin) segment of triblock copolymer, poly(L-lysin)-block-poly(ethylene glycol)-block-poly(L-lysin), was developed for the use as an effective photosensitizers in photodynamic therapy. The dynamic light scattering, atomic force microscopy showed that two nanoparticles has a relevant size of 80-150nm. The photophysical properties and singlet oxygen quantum yields of free dendrimer phthalocyanines and nanoparticles exhibited generation dependence. The intracellular uptake of dendrimer phthalocyanines in Hela cells was significantly elevated as they were incorporated into the micelles, but was inversely correlated with the generation of dendrimer phthalocyanines. The photocytotoxicity of dendrimer phthalocyanines incorporated into polymeric micelles was also increased. The presence of nanoparticles induced efficient cell death. Using a mitochondrial-sepcific dye rhodamine 123 (Rh123), our fluorescence microscopic result indicated that nanoparticles localized to the mitochondria. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Improved Methodology for Monitoring Poly(amidoamine Dendrimers Surface Transformations and Product Quality by Ultra Performance Liquid Chromatography

    Directory of Open Access Journals (Sweden)

    Chevelle A. Cason

    2008-01-01

    Full Text Available Ultra performance liquid chromatography (UPLC analysis was utilized for the first time as a methodology for monitoring poly(amidoamine (PAMAM dendrimer surface transformations and product quality. Results were compared to high-performance liquid chromatography (HPLC and were found to provide a vastly improved analytical method for the characterization of dendrimer polydispersity and variance in a typical surface modification. The application of UPLC increased the average number of theoretical plates by a factor of 7 and reduced retention times of analytes by 36%, while improving the resolution capability to discriminate surface variances in dendrimers. The new UPLC procedures were used to monitor surface modification of [core: ethylenediamine]; (G = 4; dendri-poly(amidoamine-(NH264 (i.e., [EDA]; (G4; dendri-PAMAM-(NH264 to produce biotinylated dendrimer conjugates. The enhanced sensitivity and efficiency of the UPLC analyses allowed resolution of biotin substituent levels and a better characterization of the targeted dendrimer conjugates compared to traditional HPLC methodology.

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

    Science.gov (United States)

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

    2016-01-01

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

  20. Silica nanoparticles functionalized with polyamidoamine (PAMAM) dendrimers as platforms for photoluminescence (PL) sensing of copper and cyanide ions.

    Science.gov (United States)

    Gerrans, Kateryna; Luhrs, Alicia; Feider, Clara; Margerum, Lawrence D

    2016-05-15

    Functionalized nanoparticles for photoluminescence (PL) applications are a promising technology for biomedical imaging and as sensors for small molecules. This work presents a new method to modify silica nanoparticles (SNP) using the bifunctional linker 1,1'-carbonyldiimidazole (CDI) with a series of polyamidoamine (PAMAM) dendrimer molecules followed by grafting of fluorescein isothiocyanate (FITC) or rhodamine B isothiocyanate (RITC) to create platforms for photoluminescence (PL) sensors. A dendrimer size and charge-variable response to only copper(II) ions confirmed the prediction of a selective turn-off sensor via proximity quenching. Both dye density and Cu(2+) quenching efficiency peaked with SNP-dendrimer generation 4 (64 terminal amines). In addition, changing the terminal dendrimer arms to carboxylic acid end groups increased the copper quenching suggesting that more metal ion binding sites were created in close proximity to the dyes. Of the small anions tested for a turn-off sensor, only cyanide ion fully restored the PL when reaching a 2:1 CN(-):Cu(2+) ratio, while EDTA was not as effective at the same ratio. Therefore, dendrimer size and surface charge on the nanoparticles controlled the dye loading and copper quenching efficiency, while creating multiple binding sites for cyanide over other metal binding anions. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Gd3+-Asparagine-Anionic Linear Globular Dendrimer Second-Generation G2 Complexes: Novel Nanobiohybrid Theranostics

    Directory of Open Access Journals (Sweden)

    Nasim Hashempour Alamdari

    2017-01-01

    Full Text Available Designing a unique theranostic biocompatible, biodegradable, and cost-effective agent which is easy to be synthesized as a biohybrid material was the aim of this study. In this matter, asparagine attached to anionic linear globular dendrimer G2 (as a biocompatible, biodegradable, and cost-effective agent which is negatively charged nanosized and water soluble polymer that outweighs other traditionally used dendrimers and finally contrast agent (Gd3+ was loaded (which made complexes in synthesized asparagine-dendrimer. Observations revealed that, in addition to successful colon cancer and brain targeting, Gd3+-dendrimer-asparagine, the proposed theranostic agent, could increase T1 MR relaxation times, decrease T2 MR relaxation times significantly, and improve contrast of image as well as illustrating good cellular uptake based on florescent microscopy/flow cytometry and ICP-mass data. In addition to that, it increased tumor growth inhibition percentage (TGI% significantly compared to FDA approved contrast agent, Magnevist. Totally, Gd3+-anionic linear globular dendrimer G2-asparagine could be introduced to the cancer imaging/therapy (theranostics protocols after in vivo MR and fluorescent analysis and passing clinical trials. Hence, this nanotheranostic agent would be a promising candidate for brain drug delivery and imaging in the future.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-01-01

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

  3. Repeated intravenous injections in non-human primates demonstrate preclinical safety of an anti-inflammatory phosphorus-based dendrimer.

    Science.gov (United States)

    Fruchon, Séverine; Mouriot, Sébastien; Thiollier, Thibaud; Grandin, Clément; Caminade, Anne-Marie; Turrin, Cédric-Olivier; Contamin, Hugues; Poupot, Rémy

    2015-05-01

    Dendrimers are nanosized hyperbranched polymers synthesized through an iterative step-by-step process; their size and structure are perfectly controlled, and they are widely used for biomedical purposes. Previously, we showed that a phosphorous-based dendrimer capped with anionic AzaBisPhosphonate groups (so-called ABP dendrimer) has immunomodulatory and anti-inflammatory properties toward the human immune system. It dramatically inhibits the onset and development of experimental arthritis in a mouse model relevant for human rheumatoid arthritis, a chronic inflammatory disease of auto-immune origin. In this article, we demonstrate in an unprecedented study that cynomolgus macaques repeatedly injected with the ABP dendrimer displayed no adverse response. Indeed, biochemical, haematological, clotting and immunological parameters remained with a normal physiological range during the study. Moreover, quantification of serum cytokines and histopathological analyses failed to reveal any noticeable lesion or noteworthy non-physiological occurrence. These results strengthen the potential of the ABP dendrimer as an innovative drug-candidate for the treatment of inflammatory diseases and favor the regulatory preclinical development of the molecule.

  4. Gd3+-Asparagine-Anionic Linear Globular Dendrimer Second-Generation G2 Complexes: Novel Nanobiohybrid Theranostics

    Science.gov (United States)

    Hashempour Alamdari, Nasim; Alaei-Beirami, Mahmood; Hejazinia, Hadi; Rasouli, Rahimeh; Saffari, Mostafa; Sadat Ebrahimi, Seyed Esmaeil; Assadi, Artin

    2017-01-01

    Designing a unique theranostic biocompatible, biodegradable, and cost-effective agent which is easy to be synthesized as a biohybrid material was the aim of this study. In this matter, asparagine attached to anionic linear globular dendrimer G2 (as a biocompatible, biodegradable, and cost-effective agent which is negatively charged nanosized and water soluble polymer that outweighs other traditionally used dendrimers) and finally contrast agent (Gd3+) was loaded (which made complexes) in synthesized asparagine-dendrimer. Observations revealed that, in addition to successful colon cancer and brain targeting, Gd3+-dendrimer-asparagine, the proposed theranostic agent, could increase T1 MR relaxation times, decrease T2 MR relaxation times significantly, and improve contrast of image as well as illustrating good cellular uptake based on florescent microscopy/flow cytometry and ICP-mass data. In addition to that, it increased tumor growth inhibition percentage (TGI%) significantly compared to FDA approved contrast agent, Magnevist. Totally, Gd3+-anionic linear globular dendrimer G2-asparagine could be introduced to the cancer imaging/therapy (theranostics) protocols after in vivo MR and fluorescent analysis and passing clinical trials. Hence, this nanotheranostic agent would be a promising candidate for brain drug delivery and imaging in the future. PMID:29097918

  5. Development of New Gonadotropin-Releasing Hormone-Modified Dendrimer Platforms with Direct Antiproliferative and Gonadotropin Releasing Activity.

    Science.gov (United States)

    Varamini, Pegah; Rafiee, Amirreza; Giddam, Ashwini Kumar; Mansfeld, Friederike M; Steyn, Frederik; Toth, Istvan

    2017-10-26

    Gonadotropin-releasing hormone (GnRH) agonists (e.g., triptorelin) are used for androgen suppression therapy. They possess improved stability as compared to the natural GnRH, yet they suffer from a poor pharmacokinetic profile. To address this, we used a GnRH peptide-modified dendrimer platform with and without lipidation strategy. Dendrimers were synthesized on a polylysine core and bore either native GnRH (1, 2, and 5) or lipid-modified GnRH (3 and 4). Compound 3, which bore a lipidic moiety in a branched tetramer structure, showed approximately 10-fold higher permeability and metabolic stability and 39 times higher antitumor activity against hormone-resistant prostate cancer cells (DU145) relative to triptorelin. In gonadotropin-release experiments, dendrimer 3 was shown to be the most potent construct. Dendrimer 3 showed similar luteinizing hormone (LH)-release activity to triptorelin in mice. Our findings indicate that dendrimer 3 is a promising analog with higher potency for the treatment of hormone-resistant prostate cancer than the currently available GnRH agonists.

  6. Targeted delivery of Dicer-substrate siRNAs using a dual targeting peptide decorated dendrimer delivery system.

    Science.gov (United States)

    Liu, Xiaoxuan; Liu, Cheng; Chen, Chao; Bentobji, Mélanie; Cheillan, Francine Azario; Piana, Jeanne Thomassin; Qu, Fanqi; Rocchi, Palma; Peng, Ling

    2014-11-01

    Small interfering RNAs (siRNA) are emerging as novel therapeutic agents, providing competent delivery systems that are available. Dendrimers, a special family of synthetic macromolecules, represent an exciting delivery platform by virtue of their well-defined dendritic structure and unique multivalency and cooperativity confined within a nanoscale volume. Here, we report a Dicer-substrate siRNA (dsiRNA) which, when delivered using a structurally flexible triethanolamine-core poly(amidoamine) dendrimer of generation 5 as the nanocarrier, gives rise to a much greater RNAi response than that produced with conventional siRNA. Further decoration of the dsiRNA/dendrimer complexes with a dual targeting peptide simultaneously promoted cancer cell targeting through interacting with integrins and cell penetration via the interaction with neuropilin-1 receptors, which led to improved gene silencing and anticancer activity. Altogether, our results disclosed here open a new avenue for therapeutic implementation of RNAi using dendrimer nanovector based targeted delivery. This study demonstrates superior therapeutic properties of siRNA when combined with a dendrimer-based targeted nano-delivery system. Similar approaches may eventually gain clinical utility following additional studies determining safety and efficacy. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Self-assembly of pH-responsive fluorinated dendrimer-based particulates for drug delivery and noninvasive imaging.

    Science.gov (United States)

    Criscione, Jason M; Le, Bonaire L; Stern, Eric; Brennan, Matthew; Rahner, Christoph; Papademetris, Xenophon; Fahmy, Tarek M

    2009-08-01

    Dendrimers are nanoscale macromolecules with well-defined branching chemical structures. Control over the architecture and function of these structures has enabled many advances in materials science and biomedical applications. Though dendrimers are directly synthesized by iteration of simple repetitive steps, generation of the larger, more complex structures required for many biomedical applications by covalent synthetic methods has been challenging. Here we demonstrate a spontaneous self-assembly of poly(amidoamine) dendrimers into complex nanoscopic and microscopic particulates following partial fluorination of the constituent dendrimer subunits. These dense particulates exhibit a stimulus-induced response to low external pH that causes their disassembly over time, enabling controlled release of encapsulated agents. In addition, we show that these assemblies offer a sufficiently high density of fluorine spins to enable detection of their site-specific accumulation in vivo by (19)F magnetic resonance imaging ((19)F MRI). Fluorinated dendrimer-based particulates present new features and capabilities important for a wide variety of emerging biomedical applications.

  8. Synthesis and photoluminescence study of di-dendron dendrimers derived from mono-Boc-protected ethylenediamine cores.

    Science.gov (United States)

    Zhao, Yili; Liu, Sen; Jiang, Wei; Chang, Yulei; Li, Yapeng; Fang, Xuexun; Wang, Jingyuan

    2011-01-01

    This work is focused on the synthesis and optical properties of cone-shaped structural feature di-dendron polyamidoamine dendrimers up to the third generation with mono-Boc-protected ethylenediamine (EDA) as a core. Strong UV absorbance spectra and fluorescence spectra from di-dendron dendrimers with different terminal groups (-NH(2), -COOCH(3)) were studied under different conditions by varying experimental parameters such as concentration and pH. The optical density and fluorescence intensities increased when di-dendron dendrimers generation number increased from 0.5 to 3.0. It was confirmed that the concentration of di-dendron dendrimers plays an important role in fluorescence intensity. The increase in fluorescence intensity was linear in low concentration regions, but the intensity increased slowly in high concentration regions. The results also showed a rapid increase in fluorescence intensity at low pH. The formation of a fluorescence-emitting moiety had a close relationship to protonated tertiary amine groups in di-dendron dendrimers derived from mono-Boc-protected EDA cores. Furthermore, the formation of fluorescent chemical species was irreversible. Copyright © 2010 John Wiley & Sons, Ltd.

  9. Computational Insights into the Interactions between DNA and siRNA with “Rigid” and “Flexible” Triazine Dendrimers

    Science.gov (United States)

    Pavan, Giovanni M.; Mintzer, Meredith A.; Simanek, Eric E.; Merkel, Olivia M.; Kissel, Thomas; Danani, Andrea

    2013-01-01

    In this study, simulation challenges intuitive models of “flexible” and “rigid” generation two triazine dendrimers as it pertains to solution conformation and conformation on binding DNA or siRNA sequences. These results derive from structural and energetic analyses of the binding events. Simulations of the rigid structure reinforce the role of the constrained piperazine linker in positioning the peripheral groups at significant distance from each other and the core of the dendrimer. In contrast, the flexible dendrimer, characterized by triethyleneglycol-like linkers, collapses in solution. On binding DNA and siRNA, these conformations are largely retained. The rigid dendrimer undergoes reorganization of peripheral groups to generate a large number of contacts to the nucleic acid. In contrast, the flexible dendrimer, originally conceived to create multivalent interactions with nucleic acids, generates only a few contacts and collapses further. This paper provides unique insight in the role played by molecular flexibility in the binding phenomenon. PMID:20131771

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-06-15

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

  11. Poly(amidoamine) Dendrimers Modified with 1,2-Epoxyhexane or 1,2-Epoxydodecane for Enhanced Gene Delivery Applications.

    Science.gov (United States)

    Xiao, Tongyu; Cao, Xueyan; Hou, Wenxiu; Peng, Chen; Qiu, Jieru; Shi, Xiangyang

    2015-12-01

    We report a new non-viral gene delivery system based on hydrophobically modified poly(amidoamine) (PAMAM) dendrimers. In this study, the periphery of amine-terminated generation 5 (G5) PAMAM dendrimers was partially reacted with 1,2-epoxyhexane and 1,2-epoxydodecane, respectively. The formed hydrophobically modified G5 dendrimers (denoted as G5.NH2-C6 or G5.NH2-C12) were used to complex two different plasmid DNAs (pDNAs) encoding luciferase (Luc) and enhanced green fluorescent protein (EGFP), respectively for gene transfection studies. The polyplexes formed between vectors and pDNA were characterized by gel retardation assay, dynamic light scattering, and zeta potential measurements. We show that the G5.NH2-C6 and G5.NH2-C12 vectors are able to effectively compact the pDNA, allowing for highly efficient gene transfection into a model cell line (HeLa cells) as demonstrated by both Luc assay and confocal microscopic imaging of the EGFP expression. Under the studied N/P ratios (the molar ratio of primary amines of the dendrimers to phosphates in the pDNA backbone) at 2.5 or 5, the transfection efficiency of the dendrimer-based vectors followed the order of G5.NH2-C12 > G5.NH2-C6 > G5.NH2. This enhanced gene transfection capacity is believed to be associated with the enhanced hydrophobic interaction between the vector/pDNA complexes and the relatively hydrophobic cell membranes. The developed hydrophobically modified dendrimers may be used as a promising non-viral vector for enhanced gene delivery applications.

  12. Titanium-catalysed dehydrocoupling of chiral carbosilanes

    Indian Academy of Sciences (India)

    Administrator

    Transition metal-catalysed dehydrocoupling of organosilanes containing primary, secondary and tertiary SiH groups has been developed as an effective route to short chain oligosilanes 1. Studies have been extended using NMR spectroscopy 2 to understand the underlying stereochemistry of these oligomers.

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

    Science.gov (United States)

    Schilrreff, Priscila; Mundiña-Weilenmann, Cecilia; Romero, Eder Lilia; Morilla, Maria Jose

    2012-01-01

    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. 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. The resultant 60%-67% saturated shell, 87,000-dalton G5G2.5 (mean molecular weight) interacted with cells in a significantly different fashion in comparison to their building blocks and to its closest counterpart, PAMAM G6.5. After being actively taken up by epithelial cells, G5G2.5 caused cytotoxicity only on SK-Mel-28 cells, including depletion of intracellular glutathione and fast necrosis that was manifested above 5 μM G5G2.5. It cannot be discounted

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

    Science.gov (United States)

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

    2015-10-01

    Electrogenerated chemiluminescence, ECL, reactions between tris(2,2'-bipyridine)ruthenium(II), [Ru(bpy)3](2+), and PAMAM GX.0 (X=1 and 2) dendrimers in an aqueous medium were carried out at pH10 (fully deprotonated dendrimer surface). ECL was detected in the presence of GX.0 dendrimers without addition of any known coreactant. Atomic force microscopy, AFM, measurements for GX.0 dendrimers in the presence of the [Ru(bpy)3](2+) complex were also done. AFM images showed the existence of aggregates (pillars) of globular shape, as well as interdendrimer networks forming fibers in the x-y direction for dendrimer aqueous solutions. ECL and AFM results in cooperation suggest that the coreactant effect of the end amine groups is improved by both the dendritic branched shells and the globular z-type aggregates. The ECL efficiency trends as a function of [GX.0] (whole range) can be interpreted taking into account the coreactant effect modulated by the presence of the z and x-y type aggregates. Importantly, ECL efficiency values can be taken as a measure of the change induced on the dendrimer aggregation in aqueous solutions when their concentrations rise. Redox potentials of the [Ru(bpy)3](3+/2+) couple in the presence of the G1.0 and G2.0 dendrimers were also determined. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2016-10-01

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

  16. Fabrication of triblock ABA type peptide dendrimer based on glutamic acid dimethyl ester and PEG as a potential nano drug delivery agent

    Science.gov (United States)

    Namazi, Hassan; Toomari, Yousef; Abbaspour, Hassan

    2014-01-01

    Introduction: Peptide dendrimers build up from amino acids and they simulate to artificial proteins with globular architecture. These characteristics furnish peptide dendrimers with best biodegradability and biocompatibility in drug delivery systems. Methods: A barbell-like dendrimer from glutamic acid dimethyl ester-poly (ethylene glycol)-glutamic acid dimethyl ester as ABA-type triblock copolymer (PG-PEG-PG) was prepared with liquid-phase peptide synthesis via a divergent approach. PEG 600 diacid (PEG-A) and glutamic acid dimethyl ester were used as the core and the monomeric building blocks, respectively. Linear-dendritic copolymer was prepared in the presence of DCC in pyridine. Transmission electron microscope (TEM) was used for measuring the size of first generation (G1-COOH) and second generation (G2-COOH) of dendrimer compounds. Thermal behavior of the synthesized dendrimers was investigated using DSC. Results: The desired generations G1-COOH, G2-COOH and G3-COOH were prepared by divergent method using PEG diacid 600 as a core compound. The size range of the resulted particles was found to be 20-100 nm for various generations. The isolated dendrimer was examined as the drug-delivery agent and the controlled release was carried out for drug molecule in pH 7.4. Conclusion: Based on the obtained results, the synthesized biocompatible dendrimers could potentially be utilized as a drug carrier agent. PMID:25671173

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-08-15

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

  18. Lipid-dendrimer hybrid nanosystem as a novel delivery system for paclitaxel to treat ovarian cancer.

    Science.gov (United States)

    Liu, Yuanjie; Ng, Yiwei; Toh, Ming R; Chiu, Gigi N C

    2015-12-28

    Combining lipids and dendrimers into one formulation is an emerging platform in the drug delivery field. This study aims to (i) develop and characterize a lipid-dendrimer hybrid (LDH) nanosystem for the hydrophobic anticancer drug paclitaxel, and (ii) evaluate its in vitro and in vivo anti-cancer activity in ovarian cancer models. The LDH nanosystems were prepared from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and poly (amidoamine) (PAMAM) G4.0. The size and zeta potential of the LDH nanosystem were 37.6 ± 6.1n m and +2.9 ± 0.1 mV, respectively, with vesicular morphology observed under cryo-TEM. The encapsulation efficiency of paclitaxel in the LDH system was 78.0 ± 2.1%. The potency of paclitaxel could be significantly improved by 37-fold when presented in the LDH nanosystem as compared to free drug, whereby paclitaxel and PAMAM G4.0 acted synergistically in killing the ovarian cancer cells. As shown by fluorescence confocal microscopy, majority of the lipids in the LDH nanosystem were located in the plasma membrane, while the dendrimers were distributed intracellularly upon uptake. Despite the use of a 10-fold lower paclitaxel dose, the survival of IGROV-1 ovarian tumor-bearing animals could be significantly prolonged by the paclitaxel-loaded LDH nanosystem, as reflected by a 50% increase in the median survival time. Such hybrid nanosystem emerged from combining two established drug delivery platforms could pave way for the development of multifunctional delivery systems for potential theranostic applications. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Uzun, K.; Çevik, E.; Şenel, M.; Sözeri, H.; Baykal, A.; Abasıyanık, M. F.; Toprak, M. S.

    2010-10-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-10-15

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

  1. Vibration and Fluorescence Spectra of Porphyrin- CoredBis(methylol-propionic Acid Dendrimers

    Directory of Open Access Journals (Sweden)

    Boris Minaev

    2009-03-01

    Full Text Available Bis-MPA dendron-coated free-base tetraphenylporphyrin and zinc-tetraphenyl-porphyrin (TPPH2 and TPPZn were studied in comparison with simple porphyrins (H2P, ZnP by theoretical simulation of their infrared, Raman and electronic absorption spectra, as well as fluorescense emission. Infrared and fluorescence spectra of the dendrimers were measured and interpreted along with time-resolved measurements of the fluorescence. The 0-1 emission band of the dendron substituted TPPZn was found to experience a "heavy substitution"-effect. The 0-1 vibronic emission signal is associated with a longer decay time (approx. 7 - 8 ns than the 0-0 emission (approx. 1 - 1.5 ns. The former contributed with more relative emission yield for larger dendron substituents, in agreement with the appearance of steady-state emission spectra showing increased contribution from the 0-1 vibronic fluorescence band at 650 nm. No such substitution effect was observed in the electronic or vibrational spectra of the substituted free-base variant, TPPH2. Vibration spectra of the parent porphyrins (H2P, ZnP, TPPH2 and TPPZn were calculated by density functional theory (DFT using the B3LYP/6-31G** approximation and a detailed analysis of the most active vibration modes was made based on both literature and our own experimental data. Based on the results of theoretical calculations the wide vibronic bands in the visible region were assigned. The vibronic structure also gave a qualitative interpretation of bands in the electronic absorption spectra as well as in fluorescence emission depending on the size of dendrimer substitution. From the results of time-dependent DFT calculations it is suggested that the TPPZn-cored dendrimers indicate strong vibronic interaction and increased Jahn-Teller distortion of the prophyrin core for larger dendrimer generations. Specifically, this leads to the entirely different behaviour of the emission spectra upon substitution of the TPPH2 and TPPZn

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

    Energy Technology Data Exchange (ETDEWEB)

    Arejdal, M., E-mail: arejdal.achdad@gmail.com [Laboratory of Magnetism and Physics of High Energies, Department of Physics, L.M.P.H.E (URAC-12), Faculty of Sciences, Mohammed V University, Rabat (Morocco); Bahmad, L. [Laboratory of Magnetism and Physics of High Energies, Department of Physics, L.M.P.H.E (URAC-12), Faculty of Sciences, Mohammed V University, Rabat (Morocco); Benyoussef, A. [Hassan II Academy of Science and Technology, Rabat (Morocco)

    2017-01-01

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

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

    DEFF Research Database (Denmark)

    Gichm, Lise; Christensen, Casper; Boas, Ulrik

    2008-01-01

    . Destabilization is markedly generation-dependent and is most pronounced for generation 3, which is also the most efficient at precipitating insulin. This suggests that proteins can interact with both dendrimer sui-face and interior. The pH-dependence reveals that interactions are mainly mediated by electrostatics......, confirmed by studies on four other proteins. Ability to precipitate and destabilize are positively correlated, in contrast to conventional small-molecule denaturants and stabilizers, indicating that surface immobilization of denaturing groups profoundly affects its interactions with proteins....

  4. New water-soluble polyanionic dendrimers and binding to acetylcholine in water by means of contact ion-pairing interactions.

    Science.gov (United States)

    Ornelas, Cátia; Boisselier, Elodie; Martinez, Victor; Pianet, Isabelle; Ruiz Aranzaes, Jaime; Astruc, Didier

    2007-12-21

    A new water-soluble polyanionic dendrimer containing 81 benzoate termini (diameter: 11+/-1 nm from DOSY NMR spectroscopy) has been synthesized; it interacts with acetylcholine cations in water-soluble assemblies in which each carboxylate terminus reversibly forms contact ion pairs and aggregates at the tether termini, as shown by 1H NMR spectroscopy.

  5. Next-generation sequencing reveals low-dose effects of cationic dendrimers in primary human bronchial epithelial cells.

    Science.gov (United States)

    Feliu, Neus; Kohonen, Pekka; Ji, Jie; Zhang, Yuning; Karlsson, Hanna L; Palmberg, Lena; Nyström, Andreas; Fadeel, Bengt

    2015-01-27

    Gene expression profiling has developed rapidly in recent years with the advent of deep sequencing technologies such as RNA sequencing (RNA Seq) and could be harnessed to predict and define mechanisms of toxicity of chemicals and nanomaterials. However, the full potential of these technologies in (nano)toxicology is yet to be realized. Here, we show that systems biology approaches can uncover mechanisms underlying cellular responses to nanomaterials. Using RNA Seq and computational approaches, we found that cationic poly(amidoamine) dendrimers (PAMAM-NH2) are capable of triggering down-regulation of cell-cycle-related genes in primary human bronchial epithelial cells at doses that do not elicit acute cytotoxicity, as demonstrated using conventional cell viability assays, while gene transcription was not affected by neutral PAMAM-OH dendrimers. The PAMAMs were internalized in an active manner by lung cells and localized mainly in lysosomes; amine-terminated dendrimers were internalized more efficiently when compared to the hydroxyl-terminated dendrimers. Upstream regulator analysis implicated NF-κB as a putative transcriptional regulator, and subsequent cell-based assays confirmed that PAMAM-NH2 caused NF-κB-dependent cell cycle arrest. However, PAMAM-NH2 did not affect cell cycle progression in the human A549 adenocarcinoma cell line. These results demonstrate the feasibility of applying systems biology approaches to predict cellular responses to nanomaterials and highlight the importance of using relevant (primary) cell models.

  6. G2 and G5 carboxyl-terminated polyamidoamine dendrimers interact differently with 1-palmitoyl-2-oleoyl phosphocholine bilayers **1

    Science.gov (United States)

    Limits on non-target tissue exposure and avoidance of metabolic changes to active agents make topical application/delivery of skin active agents highly desirable. Individually, phospholipid liposomes and polyamidoamine dendrimers are effective delivery systems of various active agents. Potentially...

  7. Poly(amidoamine) dendrimer-mediated synthesis and stabilization of silver sulfonamide nanoparticles with increased antibacterial activity.

    Science.gov (United States)

    Strydom, Schalk J; Rose, Warren E; Otto, Daniel P; Liebenberg, Wilna; de Villiers, Melgardt M

    2013-01-01

    Silver sulfadiazine (AgSD) is a topical antibiotic with limited aqueous solubility. In this study, it was shown that poly(amido amine) (PAMAM) dendrimer complexes with SD (SDZ) and silver (Ag) could be used for a bottom-up approach to synthesize highly-soluble AgSD nanoparticles (NPs). These NPs were stabilized against crystal growth by electrostatic layer-by-layer (LBL) coating with various PAMAM dendrimers. Additionally, AgNPs can be incorporated in the dendrimer shells that augmented AgSD release. NP formulation in a cream base provided a topical drug-delivery platform with enhanced antibacterial properties against burn-wound infections, comprising three nanostructures i.e., nano-AgSD, AgNPs as well as PAMAM dendrimers, in one efficient, elegant nanosystem. In this paper an elegant silver sulfadiazine-based nanoparticle complex is demonstrated with enhanced antibacterial properties and improved solubility for the treatment of burn-wound infections in a topical crème formulation. Copyright © 2013 Elsevier Inc. All rights reserved.

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

    NARCIS (Netherlands)

    Ricciardi, R.; Huskens, Jurriaan; Verboom, Willem

    2015-01-01

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

  9. Biocompatible Size-Defined Dendrimer-Albumin Binding Protein Hybrid Materials as a Versatile Platform for Biomedical Applications.

    Science.gov (United States)

    Maly, Jan; Stanek, Ondrej; Frolik, Jan; Maly, Marek; Ennen, Franka; Appelhans, Dietmar; Semeradtova, Alena; Wrobel, Dominika; Stofik, Marcel; Knapova, Tereza; Kuchar, Milan; Stastna, Lucie Cervenkova; Cermak, Jan; Sebo, Peter; Maly, Petr

    2016-04-01

    For the design of a biohybrid structure as a ligand-tailored drug delivery system (DDS), it is highly sophisticated to fabricate a DDS based on smoothly controllable conjugation steps. This article reports on the synthesis and the characterization of biohybrid conjugates based on noncovalent conjugation between a multivalent biotinylated and PEGylated poly(amido amine) (PAMAM) dendrimer and a tetrameric streptavidin-small protein binding scaffold. This protein binding scaffold (SA-ABDwt) possesses nM affinity toward human serum albumin (HSA). Thus, well-defined biohybrid structures, finalized by binding of one or two HSA molecules, are available at each conjugation step in a controlled molar ratio. Overall, these biohybrid assemblies can be used for (i) a controlled modification of dendrimers with the HSA molecules to increase their blood-circulation half-life and passive accumulation in tumor; (ii) rendering dendrimers a specific affinity to various ligands based on mutated ABD domain, thus replacing tedious dendrimer-antibody covalent coupling and purification procedures. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Science.gov (United States)

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

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

    Directory of Open Access Journals (Sweden)

    Mansoor Anbia

    2016-12-01

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

  12. 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.

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

    NARCIS (Netherlands)

    Ricciardi, R.; Huskens, Jurriaan; Verboom, Willem

    2015-01-01

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

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

    DEFF Research Database (Denmark)

    Hammerich, Ole; Hansen, Thomas; Thorvildsen, Asbjørn

    2009-01-01

    A series of polyamidoamine (PAMAM)-type dendrimers with a 1,4-phenylenediamine (PD) core is prepared from PD by procedures including Michael addition of methyl acrylate followed by aminolysis with 1,2-ethanediamine. Their one-electron oxidation potentials are determined by differential pulse volt...

  15. Ionic core–shell dendrimers with a polycationic core: structural aspects and host–guest binding properties

    NARCIS (Netherlands)

    van de Coevering, R.; Bruijnincx, P.C.A.|info:eu-repo/dai/nl/33799529X; Lutz, M.|info:eu-repo/dai/nl/304828971; Spek, A.L.|info:eu-repo/dai/nl/156517566; van Koten, G.|info:eu-repo/dai/nl/073839191; Klein Gebbink, R.J.M.|info:eu-repo/dai/nl/166032646

    2007-01-01

    The structural aspects and host–guest binding properties of ionic core–shell dendrimers [1]Br8 and [2]Br4, which bear a polycationic core and a neutral shell of Fréchet-type poly(benzyl aryl ether) dendrons, have been investigated by means of dendritic wedges [3]Br2 and [4]Br, that resemble one of

  16. 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.

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

    Science.gov (United States)

    Malý, J.; Lampová, H.; Semerádtová, A.; Štofik, M.; Kováčik, L.

    2009-09-01

    This paper presents a synthesis of a novel nanoparticle label with selective biorecognition properties based on a biotinylated silver-dendrimer nanocomposite (AgDNC). Two types of labels, a biotin-AgDNC (bio-AgDNC) and a biotinylated AgDNC with a poly(ethylene)glycol spacer (bio-PEG-AgDNC), were synthesized from a generation 7 (G7) hydroxyl-terminated ethylenediamine-core-type (2-carbon core) PAMAM dendrimer (DDM) by an N,N'-dicyclohexylcarbodiimide (DDC) biotin coupling and a NaBH4 silver reduction method. Synthesized conjugates were characterized by several analytical methods, such as UV-vis, FTIR, AFM, TEM, ELISA, HABA assay and SPR. The results show that stable biotinylated nanocomposites can be formed either with internalized silver nanoparticles (AgNPs) in a DMM polymer backbone ('type I') or as externally protected ('type E'), depending on the molar ratio of the silver/DMM conjugate and type of conjugate. Furthermore, the selective biorecognition function of the biotin is not affected by the AgNPs' synthesis step, which allows a potential application of silver nanocomposite conjugates as biospecific labels in various bioanalytical assays, or potentially as fluorescence cell biomarkers. An exploitation of the presented label in the development of electrochemical immunosensors is anticipated.

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

    Science.gov (United States)

    Wróblewska, Magdalena; Winnicka, Katarzyna

    2015-08-27

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

  19. Advantages of electrodes with dendrimer-protected platinum nanoparticles and carbon nanotubes for electrochemical methanol oxidation.

    Science.gov (United States)

    Siriviriyanun, Ampornphan; Imae, Toyoko

    2013-04-14

    Electrochemical sensors consisting of electrodes loaded with carbon nanotubes and Pt nanoparticles (PtNPs) protected by dendrimers have been developed using a facile method to fabricate them on two types of disposable electrochemical printed chips with a screen-printed circular gold or a screen-printed circular glassy carbon working electrode. The electrochemical performance of these sensors in the oxidation of methanol was investigated by cyclic voltammetry. It was revealed that such sensors possess stable durability and high electrocatalytic activity: the potential and the current density of an anodic peak in the oxidation of methanol increased with increasing content of PtNPs on the electrodes, indicating the promotion of electrocatalytic activity in relation to the amount of catalyst. The low anodic potential suggests the easy electrochemical reaction, and the high catalyst tolerance supports the almost complete oxidation of methanol to carbon dioxide. The significant performance of these sensors in the detection of methanol oxidation comes from the high electrocatalytic ability of PtNPs, excellent energy transfer of carbon nanotubes and the remarkable ability of dendrimers to act as binders. Thus these systems are effective for a wide range of applications as chemical, biomedical, energy and environmental sensors and as units of direct methanol fuel cells.

  20. A Nano-in-Nano Polymer-Dendrimer Nanoparticle-Based Nanosystem for Controlled Multidrug Delivery.

    Science.gov (United States)

    Zhao, Zongmin; Lou, Song; Hu, Yun; Zhu, Jie; Zhang, Chenming

    2017-08-07

    Codelivery of multiple chemotherapeutics with different action mechanisms is a promising strategy for cancer treatment. In this study, we developed a novel polymer-dendrimer hybrid nanoparticle-based nanosystem for efficient and controlled codelivery of two model chemotherapeutics, doxorubicin (DOX) and paclitaxel (PTX). The nanosystem was characterized to have a nano-in-nano structure with a size of around 150 nm. The model drugs could feasibly be loaded into the nanosystem ratiometrically with high drug-loading contents by controlling the feeding drug ratios. Also, the model drugs could be released from the nanosystem following a sequential release manner-specifically, quick PTX release and sustained DOX release. Acidic pH was found to enhance the release of both drugs. Moreover, the nanosystem was taken up by cancer cells rapidly and efficiently, and the delivered drugs could release sustainably and efficiently in cells to reach their action targets. In vitro cytotoxicity results demonstrated that, by optimizing drug ratios, the dual-drug-loaded nanosystem could result in better antitumor efficacy than the single-drug-loaded nanosystem or free dual-drug combination. Furthermore, the dual-drug-loaded nanosystem could induce significant changes in both the nucleus and tubulin patterns synergistically. All data suggest that the nano-in-nano polymer-dendrimer hybrid nanoparticle-based nanosystem is a promising candidate to achieve controlled multidrug delivery for effective combination cancer therapy.

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

    Science.gov (United States)

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

    2016-05-01

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

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

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    Jean-Pierre Majoral

    2013-09-01

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

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

    Science.gov (United States)

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

    2016-11-15

    The present investigation was aimed at developing various ligands-anchored dendrimers and comparing their brain targeting potential at one platform. Sialic acid (S), glucosamine (G) and concanavalin A (C) anchored poly(propyleneimine) (PPI) dendritic nanoconjugates were developed and evaluated for delivery of anti-cancer drug, paclitaxel (PTX) to the brain. MTT assay on U373MG human astrocytoma cells indicated IC50 values of 0.40, 0.65, 0.95, 2.00 and 3.50μM for PTX loaded SPPI, GPPI, CPPI, PPI formulations, and free PTX, respectively. The invivo pharmacokinetics and biodistribution studies in rats showed significantly higher accumulation of PTX in brain as compared to free PTX. The order of targeting potential of various ligands under investigation was found as sialic acid>glucosamine>concanavalin A. Thus, it can be concluded that sialic acid, glucosamine and Con A can be used as potential ligands to append PPI dendrimers for enhanced delivery of anticancer drugs to the brain for higher therapeutic outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2015-10-01

    Polymer mediated drug delivery system represents a novel promising platform for tumor-targeting with reduced systemic side effects and improved chemotherapeutical efficacy. In this study, we report the preparation and characterization of herceptin targeted, diglycolamic acid (DGA) functionalized polyamidoamine (PAMAM) dendrimer as a potent drug carrier for cisplatin. DGA dendrimers carrying cisplatin demonstrated enhanced anticancer activity when targeted with herceptin. In vitro cell line studies with herceptin-DGA-G4-cisplatin in HER-2 +ve and HER-2 -ve human ovarian cancer cell lines showed that these nanoparticles possessed remarkable features such as lower IC50 value, improved S-phase arrest, and enhanced apoptosis due to increased cellular uptake and accumulation than the untargeted DGA-G4-cisplatin and free cisplatin. Furthermore, in vivo results in SCID mice bearing SKOV-3 tumor xenografts, herceptin-DGA-G4-cisplatin, appeared to be more effective in inducing tumor regression as compared to free cisplatin. Collectively, these results indicate that herceptin targeted DGA functionalized PAMAM-cisplatin conjugates serve as better anti-tumor agents than individual therapeutic agents. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2008-06-01

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

  6. Efficient Transfection of siRNA by Peptide Dendrimer-Lipid Conjugates.

    Science.gov (United States)

    Kwok, Albert; Eggimann, Gabriela A; Heitz, Marc; Reymond, Jean-Louis; Hollfelder, Florian; Darbre, Tamis

    2016-12-02

    Efficient delivery of small interfering RNA (siRNA) into cells is the basis of target-gene-specific silencing and, ultimately, gene therapy. However, current transfection reagents are relatively inefficient, and very few studies provide the sort of systematic understanding based on structure-activity relationships that would provide rationales for their improvement. This work established peptide dendrimers (administered with cationic lipids) as siRNA transfection reagents and recorded structure-activity relationships that highlighted the importance of positive charge distribution in the two outer layers and a hydrophobic core as key features for efficient performance. These dendrimer-based transfection reagents work as well as highly optimised commercial reagents, yet show less toxicity and fewer off-target effects. Additionally, the degrees of freedom in the synthetic procedure will allow the placing of decisive recognition features to enhance and fine-tune transfection and cell specificity in the future. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Biomedical Applications of Modified Carbon Glassy Electrode Sensor with Nanoparticles and Dendrimers

    Directory of Open Access Journals (Sweden)

    Solomon W. LEUNG

    2011-04-01

    Full Text Available We previously reported the development of a biosensor platform that is capable of measuring biometabolites and environmental sensitive species, such as peroxide and nitrate/nitrate, to concentrations in the order of ppb (parts per billion or lower. In this investigation, we modified our platform with dendrimers to enhance its performance. Zero and second generation of dendrimers were coated on the surface of a carbon glassy electrode which was then modified with l-glutamate dehydrogenase (GDH and α-keto glutarate. The resulting electrode was tested with ammonium solutions, concentrations ranged from 2 to 300 nM at pH 7.4; the results were satisfactory. Measurements at lower concentrations had better resolution than at higher concentrations and it is believed that the measurement limit can be lower than 2 nM. This biosensor platform was proven to be versatile and can be employed as a platform for ultrasensitive detecting devices in many biomedical and environmental applications.

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

    Directory of Open Access Journals (Sweden)

    Hwankyu Lee

    2014-03-01

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

  9. Unique solution properties of quaternized oligomeric surfactants derived from ethylenediamine or G0 poly (amidoamine) dendrimers.

    Science.gov (United States)

    Yoshimura, Tomokazu; Abe, Shunsuke; Esumi, Kunio

    2012-01-01

    New quaternized oligomeric surfactants containing 4 or 8 alkyl chains were synthesized using ethylenediamine or poly(amidoamine) dendrimers as the central scaffold. Electrical conductivity, surface tension, and pyrene fluorescence measurements, as well as dynamic light scattering were used to characterize their properties. In addition, the dependence of these properties on the alkyl chain length, number of chains, and dendrimer generation was determined through comparison with previously reported oligomeric surfactants. The relation between surface tension and concentration for the oligomeric surfactants exhibited clear breakpoints, which reflect the critical micelle concentration (cmc). Both cmc and surface tension were lower than those of monomeric alkyltrimethylammonium bromide surfactants, indicating that the synthesized oligomeric surfactants have excellent micelle-forming ability in solution and high adsorption ability at the air/water interface, in spite of the large bulky structure containing multiple alkyl chains and headgroups within one molecule. When the alkyl chain length or the number of chains of the oligomeric surfactants was increased, a unique behavior was observed in that adsorption at the air/water interface and solution aggregation occurred simultaneously at a concentration below cmc (as determined by the surface tension method). This suggests that aggregate formation occurs readily in solution along with the adsorption at the interface because of strong attractive interactions between multiple alkyl chains.

  10. Second-generation supramolecular dendrimer with a defined structure due to orthogonal binding.

    Science.gov (United States)

    Eckelmann, Jens; Dethlefs, Christiane; Brammer, Stefan; Doğan, Ahmet; Uphoff, Andreas; Lüning, Ulrich

    2012-07-02

    A second-generation supramolecular dendrimer has been prepared by orthogonal multiple hydrogen bonding. In the first (inner) recognition domain, the interaction of one bis-isocyanuric acid (25) with two branching units (21) that carry complementary Hamilton receptors has been exploited. In the second (outer) generation, the two ADDA (A=hydrogen-bond acceptor, D=donor) receptors of each branching unit (21) have bound complementary DAAD units (4). The problem of limited solubility of the building blocks has been overcome by the introduction of branched ethylhexyl residues and by the use of flexible alkylene or oligo(ethylene glycol) linking chains. The orthogonal binding of the two hydrogen-bonding pairs was elucidated by chemical induced shift NMR titrations, which proved that the two pairs, isocyanuric acid with the Hamilton receptor and ADDA with DAAD, bind preferentially. The formation of the supramolecular self-assembled 1:2:4 dendrimer with a molecular weight of 5065 g mol(-1) was investigated by diffusion NMR spectroscopy. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. 177Lu-Dendrimer Conjugated to Folate and Bombesin with Gold Nanoparticles in the Dendritic Cavity: A Potential Theranostic Radiopharmaceutical

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    Héctor Mendoza-Nava

    2016-01-01

    Full Text Available 177Lu-labeled nanoparticles conjugated to biomolecules have been proposed as a new class of theranostic radiopharmaceuticals. The aim of this research was to synthesize 177Lu-dendrimer(PAMAM-G4-folate-bombesin with gold nanoparticles (AuNPs in the dendritic cavity and to evaluate the radiopharmaceutical potential for targeted radiotherapy and the simultaneous detection of folate receptors (FRs and gastrin-releasing peptide receptors (GRPRs overexpressed in breast cancer cells. p-SCN-Benzyl-DOTA was conjugated in aqueous-basic medium to the dendrimer. The carboxylate groups of Lys1Lys3(DOTA-bombesin and folic acid were activated with HATU and also conjugated to the dendrimer. The conjugate was mixed with 1% HAuCl4 followed by the addition of NaBH4 and purified by ultrafiltration. Elemental analysis (EDS, particle size distribution (DLS, TEM analysis, UV-Vis, and infrared and fluorescence spectroscopies were performed. The conjugate was radiolabeled using 177LuCl3 or 68GaCl3 and analyzed by radio-HPLC. Studies confirmed the dendrimer functionalization with high radiochemical purity (>95%. Fluorescence results demonstrated that the presence of AuNPs in the dendritic cavity confers useful photophysical properties to the radiopharmaceutical for optical imaging. Preliminary binding studies in T47D breast cancer cells showed a specific cell uptake (41.15±2.72%. 177Lu-dendrimer(AuNP-folate-bombesin may be useful as an optical and nuclear imaging agent for breast tumors overexpressing GRPR and FRs, as well as for targeted radiotherapy.

  12. Effects of PAMAM dendrimers with various surface functional groups and multiple generations on cytotoxicity and neuronal differentiation using human neural progenitor cells.

    Science.gov (United States)

    Zeng, Yang; Kurokawa, Yoshika; Win-Shwe, Tin-Tin; Zeng, Qin; Hirano, Seishiro; Zhang, Zhenya; Sone, Hideko

    2016-01-01

    Polyamidoamine (PAMAM) dendrimers have potential for biological applications as delivery systems for genes, drugs, and imaging agents into the brain, but their developmental neurotoxicity remains unknown. We investigated the effects of PAMAM dendrimers with various surface functional groups and multiple generations on neuronal differentiation using human neural progenitor cells at an equal mass concentration. Only PAMAM dendrimers containing amine (NH2) surface groups at concentrations of 10 μg/mL significantly reduced cell viability and neuronal differentiation, compared with non-amine-terminated dendrimers. PAMAM-NH2 with generation (G)3, G4, G5 G6, and G7 significantly decreased cell viability and inhibited neuronal differentiation from a concentration of 5 μg/mL, but G0, G1, and G2 dendrimers did not have any effect at this concentration. Cytotoxicity indices of PAMAM-NH2 dendrimers at 10 μg/mL correlated well with the zeta potentials of the particles. Surface group density and particle number in unit volume is more important characteristic than particle size to influence cytotoxicity for positive changed dendrimers. PAMAM-50% C12 at 1 μg/mL altered the expression level of the oxidative stress-related genes, ROR1, CYP26A1, and TGFB1, which is a DNA damage response gene. Our results indicate that PAMAM dendrimer exposure may have a surface charge-dependent adverse effect on neuronal differentiation, and that the effect may be associated with oxidative stress and DNA damage during development of neural cells.

  13. Pharmacokinetics of Chiral Dendrimer-Triamine-Coordinated Gd-MRI Contrast Agents Evaluated by in Vivo MRI and Estimated by in Vitro QCM

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    Yuka Miyake

    2015-12-01

    Full Text Available Recently, we developed novel chiral dendrimer-triamine-coordinated Gd-MRI contrast agents (Gd-MRI CAs, which showed longitudinal relaxivity (r1 values about four times higher than that of clinically used Gd-DTPA (Magnevist®, Bayer. In our continuing study of pharmacokinetic differences derived from both the chirality and generation of Gd-MRI CAs, we found that the ability of chiral dendrimer Gd-MRI CAs to circulate within the body can be directly evaluated by in vitro MRI (7 T. In this study, the association constants (Ka of chiral dendrimer Gd-MRI CAs to bovine serum albumin (BSA, measured and calculated with a quartz crystal microbalance (QCM in vitro, were found to be an extremely easy means for evaluating the body-circulation ability of chiral dendrimer Gd-MRI CAs. The Ka values of S-isomeric dendrimer Gd-MRI CAs were generally greater than those of R-isomeric dendrimer Gd-MRI CAs, which is consistent with the results of our previous MRI study in vivo.

  14. 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.

  15. 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.

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

    Science.gov (United States)

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

    2017-03-15

    In the current study camptothecin-loaded pegylated PAMAM dendrimer were synthesized and were functionalized with AS1411 anti-nucleolin aptamers for site-specific targeting against colorectal cancer cells which over expresses nucleolin receptors. The morphological properties and size dispersity of the prepared nanoparticles were evaluated using transmission electron microscope (TEM) and DLS. The drug-loading content and encapsulation efficiency were obtained 8.1% and 93.67% respectively. The in vitro release of camptothecin from the formulation was provided the sustained release of encapsulated camptothecin during 4days. Comparative in vitro cytotoxicity experiments demonstrated that the targeted camptothecin loaded-pegylated dendrimers had higher antiproliferation activity, towards nucleolin-positive HT29 and C26 colorectal cancer cells than nucleolin-negative CHO cell line. Fluorscence microscopy and flow cytometry also confirmed the enhanced cellular uptake of AS1411 targeted pegylated-dendrimer. In vivo study in C26 tumor-bearing BALB/C mice revealed that the AS1411-functionalized camptothecin loaded pegylated dendrimers improved antitumor activity and survival rate of the encapsulated camptothecin. Conjugation of AS1411 aptamer to the camptothecin loaded-pegylated dendrimer surface provides site-specific delivery of camptothecin, inhibit C26 tumor growth in vivo and significantly decrease systemic toxicity. These results suggested that the new nucleolin-targeted pegylated PAMAM dendrimer as a delivery system for camptothecin have the potential for the treatment of nucleolin-overexpressed colorectal cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Near-Infrared-Triggered Photodynamic Therapy toward Breast Cancer Cells Using Dendrimer-Functionalized Upconversion Nanoparticles

    Science.gov (United States)

    Wang, Bing-Yen; Liao, Ming-Liang; Hong, Guan-Ci

    2017-01-01

    Water-soluble upconversion nanoparticles (UCNPs) that exhibit significant ultraviolet, blue, and red emissions under 980-nm laser excitation were successfully synthesized for performing near infrared (NIR)-triggered photodynamic therapy (PDT). The lanthanide-doped UCNPs bearing oleate ligands were first exchanged by citrates to generate polyanionic surfaces and then sequentially encapsulated with NH2-terminated poly(amido amine) (PAMAM) dendrimers (G4) and chlorine6 (Ce6) using a layer-by-layer (LBL) absorption strategy. Transmission electron microscopy and X-ray diffraction analysis confirm that the hybrid UCNPs possess a polygonal morphology with an average dimension of 16.0 ± 2.1 nm and α-phase crystallinity. A simple calculation derived through thermogravimetric analysis revealed that one polycationic G4 dendrimer could be firmly accommodated by approximately 150 polyanionic citrates through multivalent interactions. Moreover, zeta potential measurements indicated that the LBL fabrication results in the hybrid nanoparticles with positively charged surfaces originated from these dendrimers, which assist the cellular uptake in biological specimens. The cytotoxic singlet oxygen based on the photosensitization of the adsorbed Ce6 through the upconversion emissions can be readily accumulated by increasing the irradiation time of the incident lasers. Compared with that of 660-nm lasers, NIR-laser excitation exhibits optimized in vitro PDT effects toward human breast cancer MCF-7 cells cultured in the tumorspheres, and less than 40% of cells survived under a low Ce6 dosage of 2.5 × 10−7 M. Fluorescence microscopy analysis indicated that the NIR-driven PDT causes more effective destruction of the cells located inside spheres that exhibit significant cancer stem cell or progenitor cell properties. Moreover, an in vivo assessment based on immunohistochemical analysis for a 4T1 tumor-bearing mouse model confirmed the effective inhibition of cancer cell proliferation

  18. Regulatory activity of azabisphosphonate-capped dendrimers on human CD4+ T cell proliferation enhances ex-vivo expansion of NK cells from PBMCs for immunotherapy

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    Caminade Anne-Marie

    2009-09-01

    Full Text Available Abstract Background Adoptive cell therapy with allogenic NK cells constitutes a promising approach for the treatment of certain malignancies. Such strategies are currently limited by the requirement of an efficient protocol for NK cell expansion. We have developed a method using synthetic nanosized phosphonate-capped dendrimers allowing such expansion. We are showing here that this is due to a specific inhibitory activity towards CD4+ T cell which could lead to further medical applications of this dendrimer. Methods Mononuclear cells from human peripheral blood were used to investigate the immunomodulatory effects of nanosized phosphonate-capped dendrimers on interleukin-2 driven CD4+T cell expansion. Proliferation status was investigated using flow cytometry analysis of CFSE dilution and PI incorporation experiments. Magnetic bead cell sorting was used to address activity towards individual or mixed cell sub-populations. We performed equilibrium binding assay to assess the interaction of fluorescent dendrimers with pure CD4+ T cells. Results Phosphonate-capped dendrimers are inhibiting the activation, and therefore the proliferation; of CD4+ T cells in IL-2 stimulated PBMCs, without affecting their viability. This allows a rapid enrichment of NK cells and further expansion. We found that dendrimer acts directly on T cells, as their regulatory property is maintained when stimulating purified CD4+ T cells with anti-CD3/CD28 microbeads. Performing equilibrium binding assays using a fluorescent analogue, we show that the phosphonate capped-dendrimers are specifically interacting with purified CD4+ T cells. Ultimately, we found that our protocol prevents the IL-2 related expansion of regulatory T cells that would be deleterious for the activity of infused NK cells. Conclusion High yield expansion of NK cells from human PBMCs by phosphonate-capped dendrimers and IL-2 occurs through the specific inhibition of the CD4+ lymphocyte compartment. Given the

  19. Synthesis and characterization of polyglycerols dendrimers for applications in tissue engineering biological

    Energy Technology Data Exchange (ETDEWEB)

    Passos, E.D.; Queiroz, A.A.A. de [Universidade Federal de Itajuba (UNIFEI), MG (Brazil)

    2014-07-01

    Full text: Introduction: Over the last twenty years is the growing development in the manufacture of synthetic scaffold in tissue engineering applications. These new materials are based on polyglycerol dendrimers (PGLD's). PGLD's are highly functional polymers with hydroxymethyl side groups, fulfill all structural prerequisites to replace poly(ethylene glycol)s in medical applications. Furthermore, since these materials are based on naturally occurring compounds that degrades over time in the body and can be safely excreted. The objective of this work was the synthesis, physicochemical, biological characterization of HPGL's with potential use as scaffolds in tissue engineering. HPGL's with oligomeric cores, of diglycerol triglycerol and tetraglycerol was used. Theoretical and Experimental Simulation Details: The synthesis of PGLD procedures involves the etherification of glycerol through anionic polymerization of glycidol. The PGLD's were characterized by chromatographic techniques (SEC and HPLC), spectroscopic (FTIR, 1H-NMR and 13C - NMR) electrochemical (zeta potential) and thermal analysis (DSC and TGA) techniques. The structure- activity relationships (SAR's) of compound prototype and its analogs were studied to determine the generation number (G) of the molecule responsible for the biological activity on the adhesion and cell proliferation process. A detailed study of the structure of PGLD's of G=0-4 was performed using the Hyperchem 7. 5 and Gromacs 4 software packages. The biocompatibility studies were studied by scanning electron microscopy (SEM) and fluorescence microscopy (EPF) technique after PGLD (G=0-4) blood contact. The overall electro-negativity/total charge density, dipole moment, frontier orbital's (HOMO - LUMO) and electrostatic potential maps (EPM) were calculated. The most stable form of the resulting compounds was determined by estimating the hydration energy and energy conformation. Results and

  20. Development and characterization of surface engineered PPI dendrimers for targeted drug delivery.

    Science.gov (United States)

    Kaur, Avleen; Jain, Keerti; Mehra, Neelesh Kumar; Jain, N K

    2017-05-01

    In this study, we reported folate-conjugated polypropylene imine dendrimers (FA-PPI) as efficient carrier for model anticancer drug, methotrexate (MTX), for pH-sensitive drug release, selective targeting to cancer cells, and anticancer activity. In the in vitro drug release studies this nanoconjugate of MTX showed initial rapid release followed by gradual slow release, and the drug release was found to be pH sensitive with greater release at acidic pH. The ex vivo investigations with human breast cancer cell lines, MCF-7, showed enhanced cytotoxicity of MTX-FA-PPI with significantly enhanced intracellular uptake. The biofate of nanoconjugate was determined in Wistar rat where MTX-FA-PPI showed 37.79-fold increase in the concentration of MTX in liver after 24 h in comparison with free MTX formulation.

  1. Supramolecular Assemblies of Poly(propyleneimine) Dendrimers Driven by Simple Monovalent Counterions

    Science.gov (United States)

    Eghtesadi, Seyed Ali; Haso, Fadi; Kashfipour, Marjan Alsadat; Lillard, Robert, , Dr.; Liu, Tianbo, , Dr.; Tianbo Liu's Group Team, Dr.; Lillard's Group Collaboration, Dr.

    Polyelectrolytes (PE) are fascinating class of polymers carrying dissociative ionic groups which give them unique properties in solutions and at charged surfaces. The properties of these polymers in solution are mainly depending on the fraction of dissociated ionic groups, the quality of solvent and salt concentration. Describing the solution properties of polyelectrolytes have always been an obstacle for polymer scientists due to their different behavior as a result of their dual character of being highly charged electrolytes and at macromolecular size. The question we tried to address was what happens to solution behavior of charged polyelectrolytes when they reach to the nano-scale size which can neither be considered as point charges nor colloids. Second generation of poly(propyleneimine) dendrimer in different solvent qualities, salt concentrations, pH and temperatures were studied using techniques such as LLS, TEM, AFM and zeta-potential, and dominant controlling factors over their self-assembly into hollow spherical ``Blackberry'' like nanoparticles was investigated.

  2. Lateral flow immunoassay with the signal enhanced by gold nanoparticle aggregates based on polyamidoamine dendrimer.

    Science.gov (United States)

    Shen, Guangyu; Xu, Hui; Gurung, Anant S; Yang, Yunhui; Liu, Guodong

    2013-01-01

    In order to amplify the signal in a gold nanoparticle-based lateral flow immunoassay, a simple and sensitive method utilizing gold nanoparticle aggregates as a colored reagent formed with a polyamidoamine dendrimer was developed. The results were compared with that achieved by employing the individual nanoparticles used in the conventional lateral flow immunoassay. Under the optimized experimental conditions, a detection limit of 0.1 ng mL⁻¹ for rabbit immunoglobulin G was achieved, which is almost 20-fold lower than that of the traditional method using individual gold nanoparticles. We believe that this simple, practical bioassay platform will be of interest for use in areas such as disease diagnostics, pathogen detection, and quality monitoring of food and water.

  3. Covalent immobilization of lipases on monodisperse magnetic microspheres modified with PAMAM-dendrimer

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Weiwei [Lanzhou University, State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Institute of Biochemical Engineering and Environmental Technology (China); Zhang, Yimei [Suzhou Research Academy of North China Electric Power University (China); Hou, Chen; Pan, Duo; He, Jianjun; Zhu, Hao, E-mail: zhuhao07@lzu.edu.cn [Lanzhou University, State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Institute of Biochemical Engineering and Environmental Technology (China)

    2016-02-15

    This paper reported an immobilization of Candida rugosa lipase (CRL) onto PAMAM-dendrimer-grafted magnetic nanoparticles synthesized by a modified solvothermal reduction method. The dendritic magnetic nanoparticles were amply characterized by several instrumental measurements, and the CRL was covalently anchored on the three generation supports with glutaraldehyde as coupling reagent. The amount of immobilized enzyme was up to 150 mg/g support and the factors related with the enzyme activity were investigated. The immobilization of lipase improved their performance in wider ranges of pH and temperature. The immobilized lipase exhibited excellent thermal stability and reusability in comparison with free enzyme and can be reused 10 cycles with the enzymatic activity remained above 90 %. The properties of lipase improved obviously after being immobilized on the dendritic supports. The inactive immobilized lipase could be regenerated with glutaraldehyde and Cu{sup 2+}, respectively. This synthetic strategy was facile and eco-friendly for applications in lipase immobilization.

  4. Nanoparticle corona for proteins: mechanisms of interaction between dendrimers and proteins.

    Science.gov (United States)

    Shcharbin, Dzmitry; Ionov, Maksim; Abashkin, Viktar; Loznikova, Svetlana; Dzmitruk, Volha; Shcharbina, Natallia; Matusevich, Ludmila; Milowska, Katarzyna; Gałęcki, Krystian; Wysocki, Stanisław; Bryszewska, Maria

    2015-10-01

    Protein absorption at the surface of big nanoparticles and formation of 'protein corona' can completely change their biological properties. In contrast, we have studied the binding of small nanoparticles - dendrimers - to proteins and the formation of their 'nanoparticle corona'. Three different types of interactions were observed. (1) If proteins have rigid structure and active site buried deeply inside, the 'nanoparticle corona' is unaffected. (2) If proteins have a flexible structure and their active site is also buried deeply inside, the 'nanoparticle corona' affects protein structure, but not enzymatic activity. (3) The 'nanoparticle corona' changes both the structure and enzymatic activity of flexible proteins that have surface-based active centers. These differences are important in understanding interactions taking place at a bio-nanointerface. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. A water-soluble triiodo amino acid and its dendrimer conjugate for computerized tomography (CT imaging

    Directory of Open Access Journals (Sweden)

    MARTIN W. BRECHBIEL

    2005-02-01

    Full Text Available Prolonging the circulation of an imaging agent is vital for making it suitable for blood pool (vascular imaging. Medical applications of vascular imaging include cardiovascular disease, abnormal capillary permeability, and tumor neovascularity. As low molecular weight computerized tomography (CT enhancement agents are characterized by inconveniently fast clearance, macromolecular compounds (both natural and synthetic have gained a wide recongnition for possessing better characteristics for performing blood imaging tasks. Herein, the syntheses and characterization of a new water-soluble triiodo amino acid, 3-[(N,N-dimethylaminoacetyl amino]-a-ethyl-2,4,6-triiodobenzenepropanoic acid (DMAA-IPA and its Starburst PAMAMgeneration 4.0 dendrimer conjugate, G-4-(DMAA-IPA37 are described. The applicability of G-4-(DMAA-IPA37 as a potential macromolecular angiographic CT contrast agent is discussed. The linear relationship between organically bound iodine concentration and CT Hounsfield units has been established thus allowing for quantification uses of CT imaging as well.

  6. The synthesis and adsorption properties of some carbohydrate-terminated dendrimer wedges

    CERN Document Server

    Ainsworth, R L

    1997-01-01

    A range of dendritic molecules that are designed to bind to a cotton surface has been synthesised. The architecture of the molecules allows the location of various functional, property modifying units at the focus and the attachment of recognition groups at the periphery of a dendritic molecule with wedge topology. The synthesis and characterisation of dendrimer wedges up to the second generation using a divergent approach has been performed. These wedges are readily built up using a simple and efficient stepwise pathway from the central core, and surface recognising species are subsequently attached to the molecule utilising procedures developed in conjunction with Unilever Research Laboratories. Work has been carried out to assess their adsorption onto a cotton surface and the postulated adsorption mechanism is discussed.

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

    Science.gov (United States)

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

    2017-03-01

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

  8. Alkyl cross-linked low molecular weight polypropyleneimine dendrimers as efficient gene delivery vectors.

    Science.gov (United States)

    Ariaee, Faezeh Moghadam; Hashemi, Maryam; Farzad, Sara Amel; Abnous, Khalil; Ramezani, Mohammad

    2016-10-01

    In recent years, polypropyleneimine (PPI) dendrimers have attracted great interest as non-viral gene delivery systems because of their attractive features including highly branched architecture with number of reactive end groups. However, without being structurally modified, they are not efficient gene carriers. In the present study, generation 2 and 3 (G2 and G3) of PPI dendrimers were conjugated with alkylcarboxylate groups as linker to enhance the transfection efficiency while maintaining their low cell toxicity. First, 10-bromodecanoic acid was covalently attached to all available surface primary amines of PPI G2 and G3 to increase their lipophilicity. In the subsequent step, PPIs were conjugated to the alkylcarboxylate groups of alkylcarboxylate-PPI derivatives to increase the number of surface primary amines. Physicochemical properties of modified PPIs were determined. Transfection experiments (using both luciferase and green fluorescent protein (GFP)- expressing plasmids) and cytotoxicity assay were performed to evaluate the efficiency of the final derivatives. Fabricated vectors condensed DNA effectively so that polyplexes with appropriate size (below 155 nm) and positive surface charge were constructed. Cross-linked low molecular weight PPIs (G2 or G3) with decanoate linkage increased transfection efficiency significantly while maintaining the low cytotoxicity. PPI G2 derivative exhibited increased buffering capacity which is believed to be responsible for better proton sponge mechanism leading to higher transfection efficiency. Our results indicated that oligomerization of low molecular weight PPI (PPI G2-alkyl-PPI G2 conjugate) could be an approach to increase the transfection efficiency and to lower the cytotoxicity of low molecular weight polycations.

  9. Dilational properties of novel amphiphilic dendrimers at water-air and water-heptane interfaces.

    Science.gov (United States)

    Zhang, Pei; Zhang, Lei; Zhang, Lu; Zhou, Jizhu; Wang, Jinben; Yan, Haike

    2012-10-25

    In this work, a series of novel amphiphilic dendrimers taking polyamidoamine dendrimer as the core with different hydrophobic tails QPAMC(m) were synthesized and the dilational properties were studied as monolayers by dilational rheological measurements at the water-air and water-n-heptane interfaces to explore the nature of adsorption behaviors. The results showed that the maximum values of the dilational modulus seemed to have no obvious variation in a wide change of hydrophobic chain length at the surface. However, there was considerable variability in the tendency of the influence of bulk concentration on the dilational modulus at the two different interfaces. It was interestingly found that the diffusion-exchange process slowed down with the increase of alkyl chain length leading to more elastic nature of adsorption film, which was contrary to the tendencies of conventional single chain and gemini surfactants. It is reasonable to consider that, in the case of the molecule having short chain length such as QPAMC(8), the alkyl chains are too short to overlap across the headgroup, enable the intermolecular hydrophobic interaction to be predominant with increasing of surface concentration, which enhances the elasticity and shows the slowest diffusion-exchange process. Whereas, when the chain length increases to 12 or 16, the alkyl chains are long enough to act intramolecularly to form intracohesion conformation, which results in enhancing the diffusion-exchange process. In conclusion, the interfacial behaviors are dictated by the size ratio between the tail and headgroup. A reasonable model with respect to the molecular interaction was proposed on the basis of experimental data. The results of interfacial tension relaxation and dynamic light scattering (DLS) experiments, in accord with the proposed mechanism, also present the unusual tendency comparing to the traditional single or gemini surfactants.

  10. Dynamics of Energy Transfer in a Conjugated Dendrimer Driven by Ultrafast Localization of Excitations.

    Science.gov (United States)

    Galindo, Johan F; Atas, Evrim; Altan, Aysun; Kuroda, Daniel G; Fernandez-Alberti, Sebastian; Tretiak, Sergei; Roitberg, Adrian E; Kleiman, Valeria D

    2015-09-16

    Solar energy conversion starts with the harvest of light, and its efficacy depends on the spatial transfer of the light energy to where it can be transduced into other forms of energy. Harnessing solar power as a clean energy source requires the continuous development of new synthetic materials that can harvest photon energy and transport it without significant losses. With chemically-controlled branched architectures, dendrimers are ideally suited for these initial steps, since they consist of arrays of chromophores with relative positioning and orientations to create energy gradients and to spatially focus excitation energies. The spatial localization of the energy delimits its efficacy and has been a point of intense research for synthetic light harvesters. We present the results of a combined theoretical experimental study elucidating ultrafast, unidirectional, electronic energy transfer on a complex molecule designed to spatially focus the initial excitation onto an energy sink. The study explores the complex interplay between atomic motions, excited-state populations, and localization/delocalization of excitations. Our findings show that the electronic energy-transfer mechanism involves the ultrafast collapse of the photoexcited wave function due to nonadiabatic electronic transitions. The localization of the wave function is driven by the efficient coupling to high-frequency vibrational modes leading to ultrafast excited-state dynamics and unidirectional efficient energy funneling. This work provides a long-awaited consistent experiment-theoretical description of excited-state dynamics in organic conjugated dendrimers with atomistic resolution, a phenomenon expected to universally appear in a variety of synthetic conjugated materials.

  11. Evaluation of cationic polyamidoamine dendrimers' dermal toxicity in the rat skin model.

    Science.gov (United States)

    Winnicka, Katarzyna; Wroblewska, Magdalena; Sosnowska, Katarzyna; Car, Halina; Kasacka, Irena

    2015-01-01

    Polyamidoamine (PAMAM) dendrimers are multi-branched, three-dimensional polymers with unique architecture, which makes these molecules attractive for medical and pharmaceutical applications. Using PAMAM as drug carriers for topical delivery might be beneficial as they only produce a transient effect without skin irritation. To evaluate the dermal toxicity of cationic PAMAM dendrimers generation 2 and generation 3, skin irritation studies were performed in vivo in the rat skin model. After 10 days topical application of various concentrations of PAMAM-NH2 (0.3 mg/mL, 3 mg/mL, 6 mg/mL, 30 mg/mL, 300 mg/mL), skin irritation was evaluated by visual, histopathological, and immunohistochemical examination. Microscopic assessment after hematoxylin-eosin staining revealed significant morphological changes of epidermal cells after application of PAMAM-NH2 at a concentration of ≥6 mg/mL. Morphological alterations of epidermal cells included cytoplasmic vacuolization of keratinocytes in the basal and spinous layers. Cytomorphological changes in keratinocytes, overall picture of the epidermis, and histopathological changes in the dermis were dose dependent. Detected alterations concerned hyperplasia of connective tissue fibers and leukocyte infiltration. Visible granulocyte infiltration in the upper dermis and sockets formed by necrotic, cornified cells in the hyperplastic foci of epithelium were also noted. Immunohistochemical analyses revealed that increased nuclear immunoreactivity to PCNA correlated with the concentration of PAMAM-NH2, but no significant differences in the cell proliferation activity in skin treated with PAMAM-NH2 generation 2 or generation 3 were observed. Significantly higher expression of PCNA extended throughout the skin layers might suggest abnormal cell proliferation, which, as a consequence, might even lead to neoplastic changes.

  12. Polymeric Carriers for Gene Delivery: Chitosan and Poly(amidoamine) Dendrimers

    Science.gov (United States)

    Xu, Qingxing; Wang, Chi-Hwa; Pack, Daniel Wayne

    2012-01-01

    Gene therapy is a potential medical solution that promises new treatments and may hold the cure for many different types of diseases and disorders of the human race. However, gene therapy is still a growing medical field and the technology is still in its infancy. The main challenge for gene therapy is to find safe and effective vectors that are able to deliver genes to the specific cells and get them to express inside the cells. Due to safety concerns, synthetic delivery systems, rather than viral vectors, are preferred for gene delivery and significant efforts have been focused on the development of this field. However, we are faced with problems like low gene transfer efficiency, cytotoxicity and lack of cell-targeting capability for these synthetic delivery systems. Over the years, we have seen a variety of new and effective polymers which have been designed and synthesized specifically for gene delivery. Moreover, various strategies that aimed at enhancing their physicochemical properties, improving transfection efficiency, reducing cytotoxicity as well as incorporating functional groups that offer better targetability and higher cellular uptake are established. Here, we look at two potential polymeric carriers, chitosan and poly(amidoamine) dendrimers, which have been widely reported for gene delivery. For chitosan, the interest arises from their availability, excellent non-cytotoxicity profile, biodegradability and ease of modification. For poly(amidoamine) dendrimers, the interest arises from their ease of synthesis with controlled structure and size, minimal cytotoxicity, biodegradability and high transfection efficiencies. The latest developments on these polymers for gene delivery will be the main focus of this article. PMID:20618156

  13. Low generation polyamine dendrimers bearing flexible tetraethylene glycol as nanocarriers for plasmids and siRNA

    Science.gov (United States)

    Sharma, Rishi; Zhang, Issan; Shiao, Tze Chieh; Pavan, Giovanni M.; Maysinger, Dusica; Roy, René

    2016-02-01

    Low G1 generation polyamine dendrimers built around programmable, flexible, and short tetraethyleneglycol branches were readily prepared in a divergent manner using a combination of orthogonal AB3 or AB5 units and highly efficient chemical transformations based on Cu(i) catalyzed alkyne-azide cycloaddition (CUAAC) and thiol-ene click reactions. The constructs showed that the G1 polyamines with only twelve and eighteen amine surface groups can successfully deliver siRNA in human cells, with transfection efficiency comparable to that of Lipofectamine 2000®. Measurements of cell viability following transfection of plasmid DNA and siRNA showed that the dendritic polyamines are less cytotoxic than Lipofectamine 2000® and are thus preferable for biological applications.Low G1 generation polyamine dendrimers built around programmable, flexible, and short tetraethyleneglycol branches were readily prepared in a divergent manner using a combination of orthogonal AB3 or AB5 units and highly efficient chemical transformations based on Cu(i) catalyzed alkyne-azide cycloaddition (CUAAC) and thiol-ene click reactions. The constructs showed that the G1 polyamines with only twelve and eighteen amine surface groups can successfully deliver siRNA in human cells, with transfection efficiency comparable to that of Lipofectamine 2000®. Measurements of cell viability following transfection of plasmid DNA and siRNA showed that the dendritic polyamines are less cytotoxic than Lipofectamine 2000® and are thus preferable for biological applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06757j

  14. A foldamer-dendrimer conjugate neutralizes synaptotoxic β-amyloid oligomers.

    Directory of Open Access Journals (Sweden)

    Lívia Fülöp

    Full Text Available BACKGROUND AND AIMS: Unnatural self-organizing biomimetic polymers (foldamers emerged as promising materials for biomolecule recognition and inhibition. Our goal was to construct multivalent foldamer-dendrimer conjugates which wrap the synaptotoxic β-amyloid (Aβ oligomers with high affinity through their helical foldamer tentacles. Oligomeric Aβ species play pivotal role in Alzheimer's disease, therefore recognition and direct inhibition of this undruggable target is a great current challenge. METHODS AND RESULTS: Short helical β-peptide foldamers with designed secondary structures and side chain chemistry patterns were applied as potential recognition segments and their binding to the target was tested with NMR methods (saturation transfer difference and transferred-nuclear Overhauser effect. Helices exhibiting binding in the µM region were coupled to a tetravalent G0-PAMAM dendrimer. In vitro biophysical (isothermal titration calorimetry, dynamic light scattering, transmission electron microscopy and size-exclusion chromatography and biochemical tests (ELISA and dot blot indicated the tight binding between the foldamer conjugates and the Aβ oligomers. Moreover, a selective low nM interaction with the low molecular weight fraction of the Aβ oligomers was found. Ex vivo electrophysiological experiments revealed that the new material rescues the long-term potentiation from the toxic Aβ oligomers in mouse hippocampal slices at submicromolar concentration. CONCLUSIONS: The combination of the foldamer methodology, the fragment-based approach and the multivalent design offers a pathway to unnatural protein mimetics that are capable of specific molecular recognition, and has already resulted in an inhibitor for an extremely difficult target.

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

    Science.gov (United States)

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

    2015-04-15

    A label-free biosensing strategy for amoxicillin (AX) allergy diagnosis based on the combination of novel dendrimer-based conjugates and a recently developed nanoplasmonic sensor technology is reported. Gold nanodisks were functionalized with a custom-designed thiol-ending-polyamido-based dendron (d-BAPAD) peripherally decorated with amoxicilloyl (AXO) groups (d-BAPAD-AXO) in order to detect specific IgE generated in patient's serum against this antibiotic during an allergy outbreak. This innovative strategy, which follows a simple one-step immobilization procedure, shows exceptional results in terms of sensitivity and robustness, leading to a highly-reproducible and long-term stable surface which allows achieving extremely low limits of detection. Moreover, the viability of this biosensor approach to analyze human biological samples has been demonstrated by directly analyzing and quantifying specific anti-AX antibodies in patient's serum without any sample pretreatment. An excellent limit of detection (LoD) of 0.6ng/mL (i.e. 0.25kU/L) has been achieved in the evaluation of clinical samples evidencing the potential of our nanoplasmonic biosensor as an advanced diagnostic tool to quickly identify allergic patients. The results have been compared and validated with a conventional clinical immunofluorescence assay (ImmunoCAP test), confirming an excellent correlation between both techniques. The combination of a novel compact nanoplasmonic platform and a dendrimer-based strategy provides a highly sensitive label free biosensor approach with over two times better detectability than conventional SPR. Both the biosensor device and the carrier structure hold great potential in clinical diagnosis for biomarker analysis in whole serum samples and other human biological samples. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hye-Ran [Department of Civil and Environmental Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 133-791 (Korea, Republic of); Jang, Jun-Won [Pohang Institute of Metal Industry Advancement, 56 Jigok-ro, Nam-gu, Pohang-si, Gyeongsangbuk-do 790-834 (Korea, Republic of); Park, Jae-Woo, E-mail: jaewoopark@hanyang.ac.kr [Department of Civil and Environmental Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 133-791 (Korea, Republic of)

    2016-11-05

    Highlights: • Carboxymethyl chitosan was attached to magnetic-cored dendrimer as terminal groups. • High sorptive capacity of carboxymethyl chitosan is added to dendritic structure. • This new adsorbent can be easily separated from water with magnetic force. • It could be reused as an adsorbent more than five-times with simple pH adjustment. - Abstract: Carboxymethyl chitosan-modified magnetic-cored dendrimers (CCMDs) were successfully synthesized in a three step method. The synthesized samples were characterized using X-ray diffraction, transmission electron microscopy, scanning electron microscopy, vibrating sample magnetometer, thermogravimetry analysis, zeta potential analyzer, X-ray photoelectron spectroscopy, surface area analysis, and Fourier transform infrared spectroscopy. The CCMD exhibited selective adsorption for anionic and cationic compounds at specific pH conditions. With the substitution of amino groups of MD with carboxymethyl chitosan moieties, the adsorption sites for cationic compounds were greatly increased. Since the adsorption onto CCMD was mainly electrostatic interaction, the adsorption of MB and MO was significantly affected by the pHs. The optimal adsorption pH values were 3 and 11 for MO and MB. The maximal adsorption of MO and MB on the CCMD at pH values of 3 and 11 were 20.85 mg g{sup −1} and 96.31 mg g{sup −1}, respectively. Reuse of the CCMD as an adsorbent was experimentally tested through adsorption and desorption with simple pH control. More than 99% and 91% of the initial adsorption of MB and MO on the CCMD was maintained with five consecutive recycling.

  17. 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).

  18. Deposition of silver nanoparticles on dendrimer functionalized multiwalled carbon nanotubes: synthesis, characterization and antimicrobial activity.

    Science.gov (United States)

    Neelgund, Gururaj M; Oki, Aderemi

    2011-04-01

    The nanohybrids composed of silver nanoparticles and aromatic polyamide functionalized multiwalled carbon nanotubes (MWCNTs) is successfully synthesized and tested for their antibacterial activity against different pathogens. Prior to deposition of silver nanoparticles, acid treated MWCNTs (MWCNTs-COOH) were successively reacted with p-phenylenediamine and methylmethacrylate to form series of NH2-terminated aromatic polyamide dendrimers on the surface of MWCNTs through Michael addition and amidation. Existence of high abundance of amine groups on the surface of functionalized MWCNTs (f-MWCNTs) provided sites for formation of silver nanoparticles by the reduction of aqueous solution of AgNO3. The silver nanoparticles formed in the resulted f-MWCNTs-Ag nanohybrids were determined to be face centered cubic (fcc) symmetry. The structure and nature of f-MWCNTs and f-MWCNTs-Ag nanohybrids were characterized by UV-vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction analysis (XRD), Raman spectroscopy and thermogravimetric analysis (TGA). The dispersion state of f-MWCNTs and immobilization of silver nanoparticles on the surface of f-MWCNTs were investigated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Elemental composition of f-MWCNTs-Ag nanohybrids was determined by energy dispersive X-ray spectroscopy (EDS). The antimicrobial activity of f-MWCNTs-Ag nanohybrids were estimated against E. coli, P. aeruginosa and S. aureu and compared with MWCNTs-COOH and f-MWCNTs. The results indicate that functionalization of MWCNTs with aromatic polyamide dendrimers and successive deposition of Ag nanoparticles could play an important role in the enhancement of antimicrobial activity.

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    Marco Marradi

    2012-06-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-02-15

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

  2. Modulation of pro-inflammatory activation of monocytes and dendritic cells by aza-bis-phosphonate dendrimer as an experimental therapeutic agent

    Science.gov (United States)

    2014-01-01

    Introduction Our objective was to assess the capacity of dendrimer aza-bis-phosphonate (ABP) to modulate phenotype of monocytes (Mo) and monocytes derived dendritic cells (MoDC) activated in response to toll-like receptor 4 (TLR4) and interferon γ (IFN- γ) stimulation. Methods Mo (n = 12) and MoDC (n = 11) from peripheral blood of healthy donors were prepared. Cells were preincubated or not for 1 hour with dendrimer ABP, then incubated with lipopolysaccharide (LPS; as a TLR4 ligand) and (IFN-γ) for 38 hours. Secretion of tumor necrosis factor α (TNFα), interleukin (IL) -1, IL-6, IL-12, IL-10 and IL-23 in the culture medium was measured by enzyme-linked immunosorbent assay (ELISA) and Cytokine Bead Array. Differentiation and subsequent maturation of MoDC from nine donors in the presence of LPS were analyzed by flow cytometry using CD80, CD86, CD83 and CD1a surface expression as markers. Results Mo and MoDC were orientated to a pro-inflammatory state. In activated Mo, TNFα, IL-1β and IL-23 levels were significantly lower after prior incubation with dendrimer ABP. In activated MoDC, dendrimer ABP promoted IL-10 secretion while decreasing dramatically the level of IL-12. TNFα and IL-6 secretion were significantly lower in the presence of dendrimer ABP. LPS driven maturation of MoDC was impaired by dendrimer ABP treatment, as attested by the significantly lower expression of CD80 and CD86. Conclusion Our data indicate that dendrimer ABP possesses immunomodulatory properties on human Mo and MoDC, in TLR4 + IFN-γ stimulation model, by inducing M2 alternative activation of Mo and promoting tolerogenic MoDC. PMID:24745366

  3. Bioreducible Fluorinated Peptide Dendrimers Capable of Circumventing Various Physiological Barriers for Highly Efficient and Safe Gene Delivery.

    Science.gov (United States)

    Cai, Xiaojun; Jin, Rongrong; Wang, Jiali; Yue, Dong; Jiang, Qian; Wu, Yao; Gu, Zhongwei

    2016-03-09

    Polymeric vectors have shown great promise in the development of safe and efficient gene delivery systems; however, only a few have been developed in clinical settings due to poor transport across multiple physiological barriers. To address this issue and promote clinical translocation of polymeric vectors, a new type of polymeric vector, bioreducible fluorinated peptide dendrimers (BFPDs), was designed and synthesized by reversible cross-linking of fluorinated low generation peptide dendrimers. Through masterly integration all of the features of reversible cross-linking, fluorination, and polyhedral oligomeric silsesquioxane (POSS) core-based peptide dendrimers, this novel vector exhibited lots of unique features, including (i) inactive surface to resist protein interactions; (ii) virus-mimicking surface topography to augment cellular uptake; (iii) fluorination-mediated efficient cellular uptake, endosome escape, cytoplasm trafficking, and nuclear entry, and (iv) disulfide-cleavage-mediated polyplex disassembly and DNA release that allows efficient DNA transcription. Noteworthy, all of these features are functionally important and can synergistically facilitate DNA transport from solution to the nucleus. As a consequences, BFPDs showed excellent gene transfection efficiency in several cell lines (∼95% in HEK293 cells) and superior biocompatibility compared with polyethylenimine (PEI). Meanwhile BFPDs provided excellent serum resistance in gene delivery. More importantly, BFPDs offer considerable in vivo gene transfection efficiency (in muscular tissues and in HepG2 tumor xenografts), which was approximately 77-fold higher than that of PEI in luciferase activity. These results suggest bioreducible fluorinated peptide dendrimers are a new class of highly efficient and safe gene delivery vectors and should be used in clinical settings.

  4. The effect of polyethylene glycol spacer chain length on the tumor-targeting potential of folate-modified PPI dendrimers

    Energy Technology Data Exchange (ETDEWEB)

    Thakur, Shrikant [Dr. Hari Singh Gour University, Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences (India); Tekade, Rakesh K., E-mail: rakeshtekade@yahoo.com [University of Hawai' i at Hilo, College of Pharmacy (United States); Kesharwani, Prashant, E-mail: prashant_pharmacy04@rediffmail.com; Jain, Narendra K., E-mail: jnarendr@yahoo.co.in [Dr. Hari Singh Gour University, Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences (India)

    2013-05-15

    The objective of the present investigation was to assess the tumor-targeting potential of ligand-spacer-engineered poly (propylene imine) (PPI) dendrimers as nanoscale drug delivery units for site-specific delivery of a model anticancer agent, docetaxel (DTX). PPI dendrimers were engineered by direct and indirect conjugation of folic acid (FA) via different types of polyethylene glycols (PEGs) [Mw (molecular weight): 1,000, 4,000, 6,000, 7,500] as spacers. The synthesized nanoconjugates (PPIFA, PPIP1FA, PPIP4FA, PPIP6FA, and PPIP7.5FA) were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance ({sup 1}H-NMR) and transmission electron microscopic (TEM) studies. Nanoconjugates were evaluated for entrapment, in vitro drug release (under various pH conditions) and hemolytic studies. Cell uptake and cytotoxicity studies were performed on human malignant cell lines (MCF-7) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide [MTT] assay. This debut study explored the effect of PEG spacer length on the targeting potential of folate-conjugated 5.0 G PPI dendrimer. DTX entrapment and in vitro drug release from nanoconjugates augmented, and hemolytic toxicity of nanoconjugates slashed with the molecular weight of PEGs. Further, nanoconjugates with PEG 4000 displayed highest tumor-targeting potential as compared to other spacer conjugated nanoconjugates due to optimized steric hindrance and receptor mediated endocytosis among other PEGs. This work is expected to shed new light on the role of spacer chain length in targeting potential of folate-anchored dendrimer.Graphical Abstract.

  5. Strain-promoted alkyne azide cycloaddition for the functionalization of poly(amide)-based dendrons and dendrimers.

    Science.gov (United States)

    Ornelas, Cátia; Broichhagen, Johannes; Weck, Marcus

    2010-03-24

    Functionalization of a poly(amido)-based dendron with ethylene glycol chains (PEG) using copper-catalyzed alkyne azide cycloaddition (CuAAC) afforded dendrons with significant levels of copper contaminations, preventing the use of such materials for biological applications. We suggest that the presence of amide, PEG, and triazole functional groups allows for copper complexation, thereby preventing the separation of the copper catalyst from the final dendron. To minimize this problem, synthetic variations on CuAAC including the addition of "click" additives for copper sequestering as well as the use of copper wire as the copper source were investigated. None of these strategies, however, resulted in copper-free products. In contrast, we developed a copper-free strain-promoted alkyne azide cycloaddition (SPAAC) strategy that functionalized poly(amide)-based dendrons and dendrimers with PEG chains quantitatively under mild reaction conditions without any metal contamination. The SPAAC products were characterized by (1)H and (13)C NMR, 2D HSQC and COSY NMR, mass spectrometry, and elemental analysis. This is the first report on the use of SPAAC for dendrimer functionalization, and the results obtained here show that SPAAC is an important tool to the dendrimer and more general biomaterials community for the functionalization of macromolecular structures due to the mild and metal-free reaction conditions, no side products, tolerance toward functional groups, and high yields.

  6. Dendrimer-Modified MoS2 Nanoflakes as a Platform for Combinational Gene Silencing and Photothermal Therapy of Tumors.

    Science.gov (United States)

    Kong, Lingdan; Xing, Lingxi; Zhou, Benqing; Du, Lianfang; Shi, Xiangyang

    2017-05-17

    Exploitation of novel hybrid nanomaterials for combinational tumor therapy is challenging. In this work, we synthesized dendrimer-modified MoS2 nanoflakes for combinational gene silencing and photothermal therapy (PTT) of cancer cells. Hydrothermally synthesized MoS2 nanoflakes were modified with generation 5 (G5) poly(amidoamine) dendrimers partially functionalized with lipoic acid via disulfide bond. The formed G5-MoS2 nanoflakes display good colloidal stability and superior photothermal conversion efficiency and photothermal stability. With the dendrimer surface amines on their surface, the G5-MoS2 nanoflakes are capable of delivering Bcl-2 (B-cell lymphoma-2) siRNA to cancer cells (4T1 cells, a mouse breast cancer cells) with excellent transfection efficiency, inducing 47.3% of Bcl-2 protein expression inhibition. In vitro cell viability assay data show that cells treated with the G5-MoS2/Bcl-2 siRNA polyplexes under laser irradiation have a viability of 21.0%, which is much lower than other groups of single mode PTT treatment (45.8%) or single mode of gene therapy (68.7%). Moreover, the super efficacy of combinational therapy was further demonstrated by treating a xenografted 4T1 tumor model in vivo. These results suggest that the synthesized G5-MoS2 nanoflakes may be employed as a potential nanoplatform for combinational gene silencing and PTT of tumors.

  7. Sugar-modified poly(propylene imine) dendrimers as drug delivery agents for cytarabine to overcome drug resistance.

    Science.gov (United States)

    Szulc, Aleksandra; Pulaski, Lukasz; Appelhans, Dietmar; Voit, Brigitte; Klajnert-Maculewicz, Barbara

    2016-11-20

    Maltose-modified poly(propylene imine) glycodendrimers (PPI-m OS) of the 4th generation provide a promising strategy for leukemia treatment. Anticancer therapy with nucleoside analog drugs such as cytarabine (Ara-C) frequently has limited efficacy due to drug resistance, inefficient uptake and accumulation of the drug inside cancer cells where it has to be transformed into the active triphosphate congener. The cationic nature of PPI dendrimers makes it possible to form complexes with nucleotide Ara-C triphosphate forms (Ara-CTP). The aim of this work was to test the concept of applying PPI glycodendrimers as drug delivery devices in order to facilitate the delivery of activated cytarabine to cancer cells to overcome metabolic limitations of the drug. The study has been carried out using 1301 and HL-60 leukemic cell lines as well as peripheral blood mononuclear cells. The results of cytotoxicity and apoptosis assays showed enhanced activity of Ara-C triphosphate form (Ara-CTP) complexed with PPI-m dendrimers in relation to free Ara-C and Ara-CTP against 1301 leukemic cells. Secondly, enhanced uptake and cytotoxicity of Ara-CTP-dendrimers complexes toward 1301 cells with blocked human equilibrative nucleoside transporter - hENT1 suggested that this combination might be a versatile candidate for chemotherapy against resistant acute lymphoblastic leukemia cells with lower expression of hENT1. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. [SWNT] / [Dendrimer

    Indian Academy of Sciences (India)

    Admin

    which is one atom thick and made up of carbon and hydrogen arranged in a chicken-wire-like mesh. Credit: Jeffrey Kysar, Columbia University. Lee,We .... Schematic device structure. A suspended SWNT is connected to four electrodes. Current/voltage is applied between electrodes 3 and 4 (''motor'' part) and the induced.

  9. 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.

  10. Triazine dendrimers as non-viral vectors for in vitro and in vivo RNAi: The effects of peripheral groups and core structure on biological activity

    Science.gov (United States)

    Merkel, Olivia M.; Mintzer, Meredith A.; Librizzi, Damiano; Samsonova, Olga; Dicke, Tanja; Sproat, Brian; Garn, Holger; Barth, Peter J.; Simanek, Eric E.; Kissel, Thomas

    2010-01-01

    A family of triazine dendrimers, differing in their core flexibility, generation number, and surface functionality, was prepared and evaluated for its ability to accomplish RNAi. The dendriplexes were analyzed with respect to their physicochemical and biological properties, including condensation of siRNA, complex size, surface charge, cellular uptake and subcellular distribution, their potential for reporter gene knockdown in HeLa/Luc cells, and ultimately their stability, biodistribution, pharmacokinetics and intracellular uptake in mice after intravenous (iv.) administration. The structure of the backbone was found to significantly influence siRNA transfection efficiency, with rigid, second generation dendrimers displaying higher gene knockdown than the flexible analogues while maintaining less off-target effects than Lipofectamine. Additionally, among the rigid, second generation dendrimers, those with either arginine-like exteriors or peripheries containing hydrophobic functionalities mediated the most effective gene knockdown, thus showing that dendrimer surface groups also affect transfection efficiency. Moreover, these two most effective dendriplexes were stable in circulation upon intravenous administration and showed passive targeting to the lung. Both dendriplex formulations were taken up into the alveolar epithelium, making them promising candidates for RNAi in the lung. The ability to correlate the effects of triazine dendrimer core scaffolds, generation number, and surface functionality with siRNA transfection efficiency yields valuable information for further modifying this non-viral delivery system and stresses the importance of only loosely correlating effective gene delivery vectors with siRNA transfection agents. PMID:20524664

  11. 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