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Effects of polyamidoamine dendrimer on neuronal differentiation from human neural progenitor cells using the neurosphere assay

ABSTRACT: Polyamidoamine (PAMAM) dendrimers have been investigated for the development of engineered nanomaterial drug delivery systems and other industrial uses. However, the major concern for their potential adverse effects on human neural progenitor cells remains unclear. In the present study, we employed human neural progenitor cells (hNPCs) to study the effects of G4-PAMAM dendrimers on neuronal differentiation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE65875 | GEO | 2015/02/13

SECONDARY ACCESSION(S): PRJNA275274

REPOSITORIES: GEO

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Effects of polyamidoamine dendrimer on neuronal differentiation from human neural progenitor cells using the neurosphere assay

Project description:Polyamidoamine (PAMAM) dendrimers have been investigated for the development of engineered nanomaterial drug delivery systems and other industrial uses. However, the major concern for their potential adverse effects on human neural progenitor cells remains unclear. In the present study, we employed human neural progenitor cells (hNPCs) to study the effects of G4-PAMAM dendrimers on neuronal differentiation. Neurospheres were treated with PAMAM dendrimer-NH2 (10 M-NM-<g/mL) for 72 h. Four neurospheres from the treatment and control groups were pooled together, and RNAs were isolated from each group.

2015-02-13 | E-GEOD-65875 | biostudies-arrayexpress

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

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

Project description:The in vivo effects of nasal exposure to polyamidoamine (PAMAM) dendrimers on their effects on gene expression in the mouse brain. A single dose of PAMAM dendrimers or saline (control) was intranasally administered to 8-week old male BALB/c mice. PAMAM-induced gene expression in the olfactory bulb, hippocampus, and cerebral cortex was measured at 24 hours after exposure to doses of 0, 0.15 mg/kg b.w. Pooled RNA from six independent experiments were analyzed at each time.

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Project description:Transcriptomic response of zebrafish embryos to Polyamidoamine (PAMAM) dendrimers

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Transcriptomic response of zebrafish embryos to Polyamidoamine (PAMAM) dendrimers

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.

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Transcriptional responses to engineered nanoplatforms for drug delivery in primary human aortic endothelial cells.

Project description:This study evaluated transcriptional effects of nanomaterials that have been proposed for use as platforms for drug delivery. We tested SiO2 that had been surface modified to have a positive zetapotential of different geometries as well PAMAM dendrimers with different surface charges. We tested these materials on human aortic endothelial cells (HAECs) since we were interested in determining if there was a toxicogenomic response in endothelial cells that may come into contact with drug delivery nanoplatforms. The most pronounced transcriptional response resulted from the SiO2 treatement - the most prevelant responses were cell cycle, lipid metabolism and pro-inflammatory responses - with fewer responses from the PAMAM dendrimers. The lipid metabolism responses may relate to teh positive surface character as this response was not observed in the G3.5-COOH dendrimers. Indeed, the G3.5-COOH dendrimers were non-toxic and did not demonstrate any consistent transcriptional response. Primary human aortic endothial cells (HAECs) were grown in 6 well plates (in 2 ml of medium) until they were >80% confluent by visual inspection. Daily media changes allowed continued growth for HAECs that demonstrate contact inhibition. The cells were then incubated with nanomaterials: surface modified SiO2 with worm and sphere goemetries (the spheres were 200 nm in diameter and the worm's cylindrical diameter 200 nm and the length was ~ 1000 nm); and PAMAM dendrimers with different surface charges (G3.5-COOH are negative and G4-NH2 are positive). RNA was collected after 4 and 24 hrs (one SiO2 worm sample was at 1.5 hrs due to space available on the 4-pack microarrays). Triplicate biological samples (indicated by the 'a', 'b', and 'c' designations in the sample names) were evaluated for gene expression changes by microarray analysis.

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Expression data from +7 hNPCs and diploid hNPCs

Project description:Human Neural progenitor cells have been found to have karyotypic abnormalities. In this study we explored the gene changes between hNPCs that are karyotypically normal and hNPCs with a trisomy of chromosome 7. We used Affymetrix GeneChips to study gene expression changes between karyotypically normal hNPCs and trisomy 7 hNPCs. Cells grown in culture for ~20 passages from diploid and + 7 hNPCs were selected for RNA extraction and hybridization on Affymetrix microarrays.

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Transcriptomic response of zebrafish embryos to Polyamidoamine (PAMAM) dendrimers

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