Gene Expression Profiles for Genotoxic Effects of Silica-Free and Silica-Coated Cobalt Ferrite Nanoparticles
Gene Expression Profiles for Genotoxic Effects of Silica-Free and Silica-Coated Cobalt Ferrite Nanoparticles
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DOI：
10.2967/jnumed.111.088443
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发表时间：
2012-01-01
影响因子：
9.3
通讯作者：
Kim, Soonhag
中科院分区：
文献类型：
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作者：
Hwang, Do Won;Lee, Dong Soo;Kim, Soonhag
纳米材料作为癌症诊断和治疗的有效载体已被广泛评价。为了将这些纳米材料应用于临床，需要验证其安全性，特别是在遗传毒性和细胞毒性方面。我们在体内和体外研究了二氧化硅包覆的钴铁氧体磁荧光纳米颗粒和无二氧化硅的钴铁氧体磁芯纳米颗粒影响的基因表达谱的变化。Ga-68标记的铁酸钴纳米颗粒的制备（对异硫氰基苄基）-1，4，7-三氮杂环壬烷-1，4，通过薄层层析法验证标记效率后，建立了7-三乙酸螯合剂。通过市售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。结果如下：与磁荧光纳米颗粒相比，磁性核纳米颗粒在不同剂量和治疗时间下显示出严重的细胞毒性作用，如通过3-（4，5-二甲基噻唑-2-基）-2，5-二苯基四唑溴化物测定所确定的。全身小动物PET和生物分布研究，包括透射电子显微镜分析，表明尾静脉注射的magneticcore或磁荧光纳米粒子表现出大量的肝脏积累。使用52个与细胞毒性相关的基因的实时聚合酶链反应阵列表明，来自磁芯处理的肝脏样品的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。磁荧光处理的肝脏样品显示基因表达约90%类似于未经处理的肝脏samples.Conclusion：我们比较了各种基因表达谱的小鼠注射磁荧光或磁性核心纳米粒子。这项研究受纳米毒性影响的基因表达谱提供了二氧化硅涂层钴铁氧体的临床使用的关键信息。
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.Methods: Ga-68-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. Results: 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 magneticcore 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.Conclusion: 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.