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粘蛋白在聚苯乙烯纳米颗粒毒理学影响中的作用

The Role of Mucin in the Toxicological Impact of Polystyrene Nanoparticles.

作者信息

Inkielewicz-Stepniak Iwona, Tajber Lidia, Behan Gavin, Zhang Hongzhou, Radomski Marek W, Medina Carlos, Santos-Martinez Maria J

机构信息

Department of Medical Chemistry, Medical University of Gdansk, 80-211 Gdańsk, Poland.

School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, the University of Dublin, Dublin 2, Ireland.

出版信息

Materials (Basel). 2018 May 3;11(5):724. doi: 10.3390/ma11050724.

Abstract

The development of novel oral drug delivery systems is an expanding area of research and both new approaches for improving their efficacy and the investigation of their potential toxicological effect are crucial and should be performed in parallel. Polystyrene nanoparticles (NPs) have been used for the production of diagnostic and therapeutic nanosystems, are widely used in food packaging, and have also served as models for investigating NPs interactions with biological systems. The mucous gel layer that covers the epithelium of the gastrointestinal system is a complex barrier-exchange system that it is mainly constituted by mucin and it constitutes the first physical barrier encountered after ingestion. In this study, we aimed to investigate the effect of polystyrene NPs on mucin and its potential role during NP⁻cell interactions. For this purpose, we evaluated the interaction of polystyrene NPs with mucin in dispersion by dynamic light scattering and with a deposited layer of mucin using a quartz crystal microbalance with dissipation technology. Next, we measured cell viability and the apoptotic state of three enterocyte-like cell lines that differ in their ability to produce mucin, after their exposure to the NPs. Positive charged NPs showed the ability to strongly interact and aggregate mucin in our model. Positive NPs affected cell viability and induced apoptosis in all cell lines independently of their ability of produce mucin.

摘要

新型口服给药系统的研发是一个不断拓展的研究领域,提高其疗效的新方法以及对其潜在毒理学效应的研究都至关重要,且应并行开展。聚苯乙烯纳米颗粒(NPs)已被用于生产诊断和治疗性纳米系统,广泛应用于食品包装,还作为研究NPs与生物系统相互作用的模型。覆盖胃肠道系统上皮的黏液凝胶层是一个复杂的屏障交换系统,主要由黏蛋白构成,是摄入后遇到的第一道物理屏障。在本研究中,我们旨在研究聚苯乙烯NPs对黏蛋白的影响及其在NP - 细胞相互作用中的潜在作用。为此,我们通过动态光散射评估了聚苯乙烯NPs与分散状态下黏蛋白的相互作用,并使用具有耗散技术的石英晶体微天平评估了与黏蛋白沉积层的相互作用。接下来,我们测量了三种产生黏蛋白能力不同的肠上皮样细胞系在暴露于NPs后的细胞活力和凋亡状态。在我们的模型中,带正电荷的NPs显示出与黏蛋白强烈相互作用并使其聚集的能力。带正电的NPs影响所有细胞系的细胞活力并诱导凋亡,且与它们产生黏蛋白的能力无关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f34/5978101/a69dc16ac6a7/materials-11-00724-g001.jpg

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