Reaction of Amino-Terminated PAMAM Dendrimers with Carbon Dioxide in Aqueous and Methanol Solutions.
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ABSTRACT:
SUBMITTER: Cheng B
PROVIDER: S-EPMC8777730 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Tecto(dendrimers) are well-defined, dendrimer cluster type covalent structures. In this article, we present the synthesis of such a PAMAM [G5:G3-(TREN)]-N-(4-carbomethoxy) pyrrolidone terminated tecto(dendrimer). This tecto(dendrimer) exhibits nontraditional intrinsic luminescence (NTIL; excitation 376 nm; emission 455 nm) that has been attributed to three fluorescent components characterized by different fluorescence lifetimes. Furthermore, it has been shown that this PAMAM [G5:G3-(TREN)]-N-(4-carbomethoxy) pyrrolidone terminated tecto(dendrimer) is able to form a polyplex with double stranded DNA, and is nontoxic for HeLa and HMEC-1 cells up to a concentration of 10 mg/mL, even though it accumulates in endosomal compartments as demonstrated by its unique NTIL emission properties. Many of the above features would portend the proposed use of this tecto(dendrimer) as an efficient transfection agent. Quite surprisingly, transfection activity could not be demonstrated in HeLa cells, and the possible reasons are discussed in the article.
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Project description:We are presenting here the application of toxicogenomics to perform the evaluation of toxic effects of two polyamidoamine dendrimers (Generation3 and Generation4) on the developing zebrafish embryo. They are nanomaterials of special concern under the toxicological point of view because of their relatively high solubility in water and bioavailability. Zebrafish embryo toxicity assays (zFET) showed that G3 was more toxic to zebrafish than G4, and that both compounds were several orders of magnitude more toxic than other carbonaceous nanomaterials, like carbon fullerenes or nanotubes. The results suggest a variety of MoA for different dendrimers, probably related to the nature and number of the chemical groups attached to their surface. They also confirm the relatively high bioavailability of these compounds, a key factor for the assessment of the risk associated to their use and release into the environment. About 5% genes were affected by the treatment. Gene ontology (GO) analyses show that these genes are involved in the oxidation-reduction process and also in the nervous system development. Representatives of each GO functional groups were selected and quantified by real-time PCR to validate the microarray data and to differentiate the action of generations of dendrimers studied.
2013-11-12 | GSE41333 | GEO
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Project description:Intrinsic, non-traditional fluorescence of polyamidoamine (PAMAM) dendrimers that do not possess classical fluorophores has been attracting considerable interest for the last decade. Many hypotheses regarding the source of the fluorescence have appeared, but some of them are still disputable. In order to shed new light on the nature of the phenomenon, we applied quenchers that are normally used to study intrinsic fluorescence of proteins (i.e., KI, CsCl, and acrylamide). KI and acrylamide efficiently quenched steady state fluorescence of PAMAM G2, PAMAM G3, and PAMAM G4 dendrimers. Stern-Volmer plots exhibited a downward curvature that has been elucidated by heterogenous emission. We assume that there are two distinct fluorescent moieties in the dendrimer structure that are characterized by different accessibility to the quenchers.
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Project description:We are presenting here the application of toxicogenomics to perform the evaluation of toxic effects of two polyamidoamine dendrimers (Generation3 and Generation4) on the developing zebrafish embryo. They are nanomaterials of special concern under the toxicological point of view because of their relatively high solubility in water and bioavailability. Zebrafish embryo toxicity assays (zFET) showed that G3 was more toxic to zebrafish than G4, and that both compounds were several orders of magnitude more toxic than other carbonaceous nanomaterials, like carbon fullerenes or nanotubes. The results suggest a variety of MoA for different dendrimers, probably related to the nature and number of the chemical groups attached to their surface. They also confirm the relatively high bioavailability of these compounds, a key factor for the assessment of the risk associated to their use and release into the environment. About 5% genes were affected by the treatment. Gene ontology (GO) analyses show that these genes are involved in the oxidation-reduction process and also in the nervous system development. Representatives of each GO functional groups were selected and quantified by real-time PCR to validate the microarray data and to differentiate the action of generations of dendrimers studied. Two different treatments were performed in this study. Zebrafish fertlized eggs were exposed to PAMAM dendrimer G3 and G4 during 48h. 3 biological replicates per studied dendrimer are included such as each control sample.
2013-11-12 | E-GEOD-41333 | biostudies-arrayexpress
Project description:Poly(amidoamine) (PAMAM) dendrimers are increasingly studied as model nanoparticles for a variety of biomedical applications, notably in systemic administrations. However, with respect to blood-contacting applications, amine-terminated dendrimers have recently been shown to activate platelets and cause a fatal, disseminated intravascular coagulation (DIC)-like condition in mice and rats. We here demonstrate that, upon addition to blood, cationic G7 PAMAM dendrimers induce fibrinogen aggregation, which may contribute to the in vivo DIC-like phenomenon. We demonstrate that amine-terminated dendrimers act directly on fibrinogen in a thrombin-independent manner to generate dense, high-molecular-weight fibrinogen aggregates with minimal fibrin fibril formation. In addition, we hypothesize this clot-like behavior is likely mediated by electrostatic interactions between the densely charged cationic dendrimer surface and negatively charged fibrinogen domains. Interestingly, cationic dendrimers also induced aggregation of albumin, suggesting that many negatively charged blood proteins may be affected by cationic dendrimers. To investigate this further, zebrafish embryos were employed to more specifically determine the speed of this phenomenon and the pathway- and dose-dependency of the resulting vascular occlusion phenotype. These novel findings show that G7 PAMAM dendrimers significantly and adversely impact many blood components to produce rapid coagulation and strongly suggest that these effects are independent of classic coagulation mechanisms. These results also strongly suggest the need to fully characterize amine-terminated PAMAM dendrimers in regard to their adverse effects on both coagulation and platelets, which may contribute to blood toxicity.
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