Kononenko Veno, Warheit David B, Drobne Damjana
Department of Biology, Biotechnical Faculty, University of Ljubljana, Večna pot 111, 1000 Ljubljana, Slovenia.
Warheit Scientific LLC, Wilmington, DE 19801, USA.
Nanomaterials (Basel). 2019 May 6;9(5):704. doi: 10.3390/nano9050704.
Poorly soluble, low (cyto)toxic particles (PSLTs) are often regarded as one group, but it is important that these particles can be further differentiated based on their bioactivity. Currently, there are no biological endpoint based groupings for inhaled nanoparticles (NPs) that would allow us to subgroup PSLTs based on their mode of action. The aim of this study was to group NPs based on their cytotoxicity and by using the in vitro response of the endo-lysosomal system as a biological endpoint. The endo-lysosomal system is a main cellular loading site for NPs. An impaired endo-lysosomal system in alveolar type II cells may have serious adverse effects on the maintenance of pulmonary surfactant homeostasis. The 15 different NPs were tested with human lung adenocarcinoma (A549) cells. The highly soluble NPs were most cytotoxic. With respect to PSLTs, only three NPs increased the cellular load of acid and phospholipid rich organelles indicating particle biopersistence. All the rest PSLTs could be regarded as low hazardous. The presented in vitro test system could serve as a fast screening tool to group particles according to their ability to interfere with lung surfactant metabolism. We discuss the applicability of the suggested test system for bringing together substances with similar modes-of-action on lung epithelium. In addition, we discuss this approach as a benchmark test for the comparative assessment of biopersistence of PSLTs.
难溶性低（细胞）毒性颗粒（PSLTs）通常被视为一类，但重要的是，这些颗粒可根据其生物活性进一步区分。目前，对于吸入纳米颗粒（NPs），尚无基于生物学终点的分组方法，无法让我们根据其作用方式对PSLTs进行亚组划分。本研究的目的是根据NPs的细胞毒性，并以内吞溶酶体系统的体外反应作为生物学终点对其进行分组。内吞溶酶体系统是NPs的主要细胞内摄取位点。肺泡II型细胞内吞溶酶体系统受损可能对肺表面活性物质稳态的维持产生严重不利影响。用人类肺腺癌（A549）细胞对15种不同的NPs进行了测试。高溶解性NPs的细胞毒性最大。对于PSLTs，只有三种NPs增加了富含酸性物质和磷脂的细胞器的细胞内摄取量，表明颗粒具有生物持久性。其余所有PSLTs均可视为低危险性。所提出的体外测试系统可作为一种快速筛选工具，根据颗粒干扰肺表面活性物质代谢的能力对其进行分组。我们讨论了所建议的测试系统在将对肺上皮具有相似作用方式的物质归为一类方面的适用性。此外，我们还讨论了这种方法作为PSLTs生物持久性比较评估的基准测试。
