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工程纳米颗粒。这位新访客对大脑有多友好?

Engineered nanoparticles. How brain friendly is this new guest?

作者信息

Cupaioli Francesca A, Zucca Fabio A, Boraschi Diana, Zecca Luigi

机构信息

Institute of Biomedical Technologies, National Research Council of Italy, Segrate, Milan, Italy.

Institute of Biomedical Technologies, National Research Council of Italy, Unit of Pisa, Pisa, Italy.

出版信息

Prog Neurobiol. 2014 Aug-Sep;119-120:20-38. doi: 10.1016/j.pneurobio.2014.05.002. Epub 2014 May 10.

Abstract

In the last 30 years, the use of engineered nanoparticles (NPs) has progressively increased in many industrial and medical applications. In therapy, NPs may allow more effective cellular and subcellular targeting of drugs. In diagnostic applications, quantum dots are exploited for their optical characteristics, while superparamagnetic iron oxides NPs are used in magnetic resonance imaging. NPs are used in semiconductors, packaging, textiles, solar cells, batteries and plastic materials. Despite the great progress in nanotechnologies, comparatively little is known to date on the effects that exposure to NPs may have on the human body, in general and specifically on the brain. NPs can enter the human body through skin, digestive tract, airways and blood and they may cross the blood-brain barrier to reach the central nervous system. In addition to the paucity of studies describing NP effects on brain function, some of them also suffer of insufficient NPs characterization, inadequate standardization of conditions and lack of contaminant evaluation, so that results from different studies can hardly be compared. It has been shown in vitro and in vivo in rodents that NPs can impair dopaminergic and serotoninergic systems. Changes of neuronal morphology and neuronal death were reported in mice treated with NPs. NPs can also affect the respiratory chain of mitochondria and Bax protein levels, thereby causing apoptosis. Changes in expression of genes involved in redox pathways in mouse brain regions were described. NPs can induce autophagy, and accumulate in lysosomes impairing their degradation capacity. Cytoskeleton and vesicle trafficking may also be affected. NPs treated animals showed neuroinflammation with microglia activation, which could induce neurodegeneration. Considering the available data, it is important to design adequate models and experimental systems to evaluate in a reliable and controlled fashion the effects of NPs on the brain, and generate data representative of effects on the human brain, thereby useful for developing robust and valid nanosafety standards.

摘要

在过去30年里,工程纳米颗粒(NPs)在许多工业和医学应用中的使用逐渐增加。在治疗方面,纳米颗粒可使药物更有效地靶向细胞和亚细胞。在诊断应用中,量子点因其光学特性而被利用,而超顺磁性氧化铁纳米颗粒则用于磁共振成像。纳米颗粒还用于半导体、包装、纺织品、太阳能电池、电池和塑料材料。尽管纳米技术取得了巨大进展,但迄今为止,人们对接触纳米颗粒可能对人体产生的影响,总体上尤其是对大脑的影响了解相对较少。纳米颗粒可通过皮肤、消化道、气道和血液进入人体,并可能穿过血脑屏障到达中枢神经系统。除了描述纳米颗粒对脑功能影响的研究较少外,其中一些研究还存在纳米颗粒表征不足、条件标准化不充分以及缺乏污染物评估等问题,因此不同研究的结果很难进行比较。在啮齿动物的体外和体内实验中已表明,纳米颗粒可损害多巴胺能和5-羟色胺能系统。在用纳米颗粒处理的小鼠中报告了神经元形态的变化和神经元死亡。纳米颗粒还可影响线粒体的呼吸链和Bax蛋白水平,从而导致细胞凋亡。描述了小鼠脑区氧化还原途径相关基因表达的变化。纳米颗粒可诱导自噬,并在溶酶体中积累,损害其降解能力。细胞骨架和囊泡运输也可能受到影响。经纳米颗粒处理的动物表现出伴有小胶质细胞激活的神经炎症,这可能诱导神经退行性变。考虑到现有数据,设计适当的模型和实验系统以可靠且可控的方式评估纳米颗粒对大脑的影响,并生成代表对人类大脑影响的数据非常重要,这对于制定稳健且有效的纳米安全标准很有用。

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