期刊
MOLECULAR PHARMACEUTICS
卷 10, 期 8, 页码 3242-3252出版社
AMER CHEMICAL SOC
DOI: 10.1021/mp400285u
关键词
silica nanoparticles; poly(amido amine) dendrimers; gene expression profile; endothelial cells
资金
- NIH [R01 DE19050]
- Utah Science Technology and Research (USTAR) Initiative
- National Cancer Institute [P30 CA042014]
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.
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