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金纳米棱柱体对小鼠和人原代及转化细胞的抗增殖和促凋亡作用的多参数分析、体内生物分布和毒性。

Multiparametric analysis of anti-proliferative and apoptotic effects of gold nanoprisms on mouse and human primary and transformed cells, biodistribution and toxicity in vivo.

机构信息

Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, 50009, Zaragoza, Spain.

Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Centro de Investigación Biomédica de Aragón (CIBA), Universidad de Zaragoza, 50009, Zaragoza, Spain.

出版信息

Part Fibre Toxicol. 2017 Oct 26;14(1):41. doi: 10.1186/s12989-017-0222-4.

Abstract

BACKGROUND

The special physicochemical properties of gold nanoprisms make them very useful for biomedical applications including biosensing and cancer therapy. However, it is not clear how gold nanoprisms may affect cellular physiology including viability and other critical functions. We report a multiparametric investigation on the impact of gold-nanoprisms on mice and human, transformed and primary cells as well as tissue distribution and toxicity in vivo after parental injection.

METHODS

Cellular uptake of the gold-nanoprisms (NPRs) and the most crucial parameters of cell fitness such as generation of reactive oxygen species (ROS), mitochondria membrane potential, cell morphology and apoptosis were systematically assayed in cells. Organ distribution and toxicity including inflammatory response were analysed in vivo in mice at 3 days or 4 months after parental administration.

RESULTS

Internalized gold-nanoprisms have a significant impact in cell morphology, mitochondrial function and ROS production, which however do not affect the potential of cells to proliferate and form colonies. In vivo NPRs were only detected in spleen and liver at 3 days and 4 months after administration, which correlated with some changes in tissue architecture. However, the main serum biochemical markers of organ damage and inflammation (TNFα and IFNγ) remained unaltered even after 4 months. In addition, animals did not show any macroscopic sign of toxicity and remained healthy during all the study period.

CONCLUSION

Our data indicate that these gold-nanoprisms are neither cytotoxic nor cytostatic in transformed and primary cells, and suggest that extensive parameters should be analysed in different cell types to draw useful conclusions on nanomaterials safety. Moreover, although there is a tendency for the NPRs to accumulate in liver and spleen, there is no observable negative impact on animal health.

摘要

背景

金纳米棒具有特殊的物理化学性质,使其非常适用于包括生物传感和癌症治疗在内的生物医学应用。然而,目前尚不清楚金纳米棒如何影响细胞生理学,包括细胞活力和其他关键功能。我们报告了一项关于金纳米棒对小鼠和人类、转化和原代细胞的影响的多参数研究,以及体内注射后纳米棒的组织分布和毒性。

方法

系统检测了细胞内金纳米棒(NPRs)的摄取以及细胞活力的关键参数,如活性氧(ROS)的产生、线粒体膜电位、细胞形态和细胞凋亡。在注射后 3 天或 4 个月,在小鼠体内分析了器官分布和毒性,包括炎症反应。

结果

内吞的金纳米棒对细胞形态、线粒体功能和 ROS 产生有显著影响,但不影响细胞增殖和形成集落的能力。在注射后 3 天和 4 个月,NPRs 仅在脾脏和肝脏中检测到,这与组织结构的一些变化有关。然而,即使在 4 个月后,器官损伤和炎症的主要血清生化标志物(TNFα 和 IFNγ)仍未改变。此外,动物在整个研究期间没有表现出任何毒性的宏观迹象,仍然健康。

结论

我们的数据表明,这些金纳米棒在转化和原代细胞中既没有细胞毒性也没有细胞增殖抑制作用,并表明应该在不同的细胞类型中分析广泛的参数,以对纳米材料的安全性得出有用的结论。此外,尽管 NPRs 有倾向于在肝脏和脾脏中积累,但对动物健康没有观察到明显的负面影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fdf/5658988/dfd9767291f8/12989_2017_222_Fig1_HTML.jpg

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