Abstract
Nanomaterials have been widely evaluated for potential use as efficient delivery carriers for cancer diagnosis and therapy. To translate these nanomaterials to the clinic, their safety needs to be verified, particularly in terms of genotoxicity and cytotoxicity. We investigated changes in gene expression profiles influenced by silica-coated cobalt ferrite magnetic-fluorescence nanoparticles and silica-free cobalt ferrite magnetic-core nanoparticles in vivo and in vitro. (68)Ga-labeled cobalt ferrite nanoparticles produced by synthesis of 2-(p-isothio-cyanatobenzyl)-1,4,7-triazacyclonane-1,4,7-triacetic acid chelator were established after labeling efficiency had been validated through a thin-layer chromatography method. The expression of genes associated with the stress and toxicity pathways was verified by a commercially available polymerase chain reaction array kit. In comparison with magnetic-fluorescence nanoparticles, magnetic-core nanoparticles revealed severe cytotoxic effects at various doses and treatment times as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Whole-body small-animal PET and biodistribution studies, including transmission electron microscope analysis, showed that tail-vein injection of magnetic-core or magnetic-fluorescence nanoparticles exhibited substantial liver accumulation. Real-time polymerase chain reaction array using 52 genes related to cellular toxicity demonstrated that 17 genes from the magnetic-core-treated liver samples were significantly affected, mostly in relation to DNA damage or repair and to oxidative or metabolic stress. The magnetic-fluorescence-treated liver samples showed gene expression approximately 90% similar to that of untreated liver samples. We compared a variety of gene expression profiles in mice injected with magnetic-fluorescence or magnetic-core nanoparticles. This study of gene expression profiles affected by nanotoxicity provides critical information for the clinical use of silica-coated cobalt ferrite.
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