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 poly­(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.