Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.
J Nucl Med. 2012 Jan;53(1):106-12. doi: 10.2967/jnumed.111.088443. Epub 2011 Dec 6.
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.
研究体内和体外二氧化硅包覆钴铁氧体磁荧光纳米粒子和无二氧化硅钴铁氧体磁核纳米粒子对基因表达谱的影响。
通过薄层层析法验证标记效率后，建立了合成 2-(对异硫氰酸苄基)-1,4,7-三氮杂环壬烷-1,4,7-三乙酸螯合剂的68Ga 标记钴铁氧体纳米粒子。通过商用聚合酶链反应阵列试剂盒验证与应激和毒性途径相关的基因表达。
与磁荧光纳米粒子相比，磁核纳米粒子在不同剂量和处理时间下通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐法显示出严重的细胞毒性作用。全身小动物 PET 和生物分布研究，包括透射电子显微镜分析，表明尾静脉注射磁核或磁荧光纳米粒子会导致大量肝脏蓄积。使用与细胞毒性相关的 52 个基因的实时聚合酶链反应阵列显示，来自磁核处理的肝样本的 17 个基因受到显著影响，主要与 DNA 损伤或修复以及氧化或代谢应激有关。磁荧光处理的肝样本的基因表达与未处理的肝样本相似，约为 90%。
我们比较了注射磁荧光或磁核纳米粒子的小鼠的多种基因表达谱。这项关于纳米毒性影响的基因表达谱研究为临床应用二氧化硅包覆钴铁氧体提供了关键信息。
