Department of Health Technologies, School of Information Technologies, Tallinn University of Technology, Tallinn, Estonia.
Toxicol In Vitro. 2018 Aug;50:11-21. doi: 10.1016/j.tiv.2018.02.010. Epub 2018 Feb 16.
The precise knowledge on various interactions of metal nanoparticles (NP) in a living organism is scarce. It is expected that metals can bind to nucleic acids, peptides and proteins (e.g. enzymes), and modify the functioning of vital cellular compartments after entering the organism. The predictive factors for quantitative nanostructure-activity relationship (QNAR) analysis could enhance efficient and harmless usage of nanoparticles (NPs) in the industry as well in the medicine. The studies value the composition of the NP corona determined by time, temperature and source of protein which has been found to implicate the physiological behaviour of NPs. One has largely been ignored: the NPs specific isoelectric point (IEP) and pH at the state of measurement. Herein, this study investigates the effect of pH and surface charge of six metal oxide (MeOx) NPs on time dependency of cytotoxicity. Several aspects of the characterization of ultrafine particles in the actual test system which is the most relevant for the interpretation of the toxicological data are referred: (i) the difference of pH in the room temperature and in the incubation conditions (ii) the difference of dispersions in MilliQ and complete cell media; (iii) the need to exemplify also the pH and isoelectric point when the hydrodynamic size is measured; (iv) the importance of time due to the time-dependent equilibration and changes of NPs corona. The surface charge determines the formation of corona and could be modified by pH. MeOx NPs without fully charge equilibrated corona might play the main role of MeOx NPs entering into the cell and consequently the time dependent manifestation of the cellular effect.
关于金属纳米粒子(NP)在生物体中各种相互作用的精确知识还很缺乏。预计金属可以与核酸、肽和蛋白质(例如酶)结合,并在进入生物体后改变重要细胞区室的功能。定量纳米结构-活性关系(QNAR)分析的预测因素可以提高纳米粒子(NP)在工业和医学中的有效和无害使用。这些研究价值由时间、温度和蛋白质来源决定的 NP 冠层的组成,这已经被发现暗示了 NPs 的生理行为。一个很大程度上被忽视了:在测量状态下 NPs 的特定等电点(IEP)和 pH 值。在此,本研究调查了六种金属氧化物(MeOx)NP 的 pH 值和表面电荷对细胞毒性时间依赖性的影响。本研究参考了实际测试系统中超细颗粒特性的几个方面,这些方面对于解释毒理学数据最为相关:(i)室温下和孵育条件下 pH 值的差异;(ii)MilliQ 和完全细胞培养基中分散度的差异;(iii)当测量水动力粒径时还需要举例说明 pH 值和等电点;(iv)由于 NP 冠层的时间依赖性平衡和变化,时间的重要性。表面电荷决定了冠层的形成,并且可以被 pH 值修饰。没有完全电荷平衡的 NP 可能会发挥 MeOx NP 进入细胞的主要作用,从而导致细胞效应的时间依赖性表现。