2 research outputs found
Transcriptional Responses of Human Aortic Endothelial Cells to Nanoconstructs Used in Biomedical Applications
Understanding
the potential toxicities of manufactured nanoconstructs
used for drug delivery and biomedical applications may help improve
their safety. We sought to determine if surface-modified silica nanoparticles
and polyÂ(amido amine) dendrimers elicit genotoxic responses on vascular
endothelial cells. The nanoconstructs utilized in this study had a
distinct geometry (spheres vs worms) and surface charge, which were
used to evaluate the contributions of these parameters to any potential
adverse effects of these materials. Time-dependent cytotoxicity was
found for surfaced-functionalized but geometrically distinct silica
materials, while amine-terminated dendrimers displayed time-independent
cytotoxicity and carboxylated dendrimers were nontoxic in our assays.
Transcriptomic evaluation of human aortic endothelial cell (HAEC)
responses indicated time-dependent gene induction following silica
exposure, consisting of cell cycle gene repression and pro-inflammatory
gene induction. However, the dendrimers did not induce genomic toxicity,
despite displaying general cytotoxicity
Nanoparticle Geometry and Surface Orientation Influence Mode of Cellular Uptake
In order to engineer safer nanomaterials, there is a need to understand, systematically evaluate, and develop constructs with appropriate cellular uptake and intracellular fates. The overall goal of this project is to determine the uptake patterns of silica nanoparticle geometries in model cells, in order to aid in the identification of the role of geometry on cellular uptake and transport. In our experiments we observed a significant difference in the viability of two phenotypes of primary macrophages; immortalized macrophages exhibited similar patterns. However, both primary and immortalized epithelial cells did not exhibit toxicity profiles. Interestingly uptake of these geometries in all cell lines exhibited very different time-dependent patterns. A screening of a series of chemical inhibitors of endocytosis was performed to isolate the uptake mechanisms of the different particles. The results show that all geometries exhibit very different uptake profiles and that this may be due to the orientation of the nanoparticles when they interact with the cell surface. Additionally, evidence suggests that these uptake patterns initialize different downstream cellular pathways, dependent on cell type and phenotype