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首页> 外文期刊>Nanoscale >Cancer cell-selective promoter recognition accompanies antitumor effect by glucocorticoid receptor-targeted gold nanoparticle
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Cancer cell-selective promoter recognition accompanies antitumor effect by glucocorticoid receptor-targeted gold nanoparticle

机译：癌症cell-selective启动子识别伴随着由糖皮质激素抗肿瘤效应receptor-targeted黄金纳米颗粒

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Nanoparticles, such as gold nanoparticles (GNP), upon convenient modifications perform multi tasks catering to many biomedical applications. However, GNP or any other type of nanoparticles is yet to achieve the feat of intracellular regulation of endogenous genes of choice such as through manipulation of a gene-promoter in a chromosome. As for gene modulation and delivery, GNP (or other nanoparticles) showed only limited gene therapy potential, which relied on the delivery of 'exogenous' genes invoking gene knockdown or replacement. Practically, there are no instances for the nanoparticle-mediated promoter regulation of"endogenous' genes, more so, as a cancer selective phenomenon. In this regard, we report the development of a simple, easily modifiable GNP-formulation, which promoted/up-regulated the expression of a specific category of 'endogenous' genes, the glucocorticoid responsive genes. This genetic up-regulation was induced in only cancer cells by modified GNP-mediated transcriptional activation of its cytoplasmic receptor, glucocorticoid receptor (GR). Normal cells and their GR remained primarily unperturbed by this GNP-formulation. The most potent gene up-regulating GNP-formulation down-regulated a cancer-specific proliferative signal, phospho-Akt in cancer cells, which accompanied retardation of tumor growth in the murine melanoma model. We show that GR-targeted GNPs may find potential use in the targeting and modulation of genetic information in cancer towards developing novel anticancer therapeutics.
机译：纳米粒子,如金纳米粒子(国民生产总值),在方便修改执行多任务迎合许多生物医学应用。然而,国民生产总值或任何其他类型的纳米粒子尚未实现细胞内的壮举调节内源性基因的选择等通过操纵一个gene-promoter染色体。国民生产总值(或其他纳米粒子)显示有限基因治疗的潜力,这依赖于交付的外源基因调用基因击倒或更换。没有nanoparticle-mediated实例“内源性基因的启动子调控,更多所以,作为一个癌症选择性现象。方面,我们报告一个简单的的发展,很容易修改的GNP-formulation,提升/差异的表达“内生”基因的特定类别糖皮质激素反应的基因。老年病只在肿瘤细胞诱导修改GNP-mediated转录激活其胞质受体、糖皮质激素受体(GR)。主要是由这个GNP-formulation镇定。最有效的基因调控GNP-formulation下调一个癌症特异性增殖信号,phospho-Akt癌症伴随着缺陷的肿瘤细胞小鼠黑色素瘤的增长模型。GR-targeted国民生产总值可能发现潜在的使用目标和调制的遗传信息癌症对开发新型抗癌疗法。

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