Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CeNIDE), University of Duisburg-Essen, Essen, Germany.
Bergmannsheil University Hospital/Surgical Research, Ruhr-University Bochum, Bochum, Germany.
Cell Biol Toxicol. 2021 Aug;37(4):573-593. doi: 10.1007/s10565-020-09571-z. Epub 2020 Nov 17.
Zinc oxide particles were synthesized in various sizes and shapes, i.e., spheres of 40-nm, 200-nm, and 500-nm diameter and rods of 40∙100 nm and 100∙400 nm (all PVP-stabilized and well dispersed in water and cell culture medium). Crystallographically, the particles consisted of the hexagonal wurtzite phase with a primary crystallite size of 20 to 100 nm. The particles showed a slow dissolution in water and cell culture medium (both neutral; about 10% after 5 days) but dissolved within about 1 h in two different simulated lysosomal media (pH 4.5 to 4.8). Cells relevant for respiratory exposure (NR8383 rat alveolar macrophages) were exposed to these particles in vitro. Viability, apoptosis, and cell activation (generation of reactive oxygen species, ROS, release of cytokines) were investigated in an in vitro lung cell model with respect to the migration of inflammatory cells. All particle types were rapidly taken up by the cells, leading to an increased intracellular zinc ion concentration. The nanoparticles were more cytotoxic than the microparticles and comparable with dissolved zinc acetate. All particles induced cell apoptosis, unlike dissolved zinc acetate, indicating a particle-related mechanism. Microparticles induced a stronger formation of reactive oxygen species than smaller particles probably due to higher sedimentation (cell-to-particle contact) of microparticles in contrast to nanoparticles. The effect of particle types on the cytokine release was weak and mainly resulted in a decrease as shown by a protein microarray. In the particle-induced cell migration assay (PICMA), all particles had a lower effect than dissolved zinc acetate. In conclusion, the biological effects of zinc oxide particles in the sub-toxic range are caused by zinc ions after intracellular dissolution, by cell-to-particle contacts, and by the uptake of zinc oxide particles into cells. Graphical headlights • The cytotoxicity of zinc oxide particles is mainly due to the intracellular release of zinc ions. • The size and shape of zinc oxide micro- and nanoparticles has only small effects on lung cells in the sub-toxic range. • Zinc oxide particles are rapidly taken up by cells, regardless of their size and shape. • Zinc oxide particles rapidly dissolve after cellular uptake in endolysosomes.
氧化锌颗粒被合成出不同的尺寸和形状，例如，40nm、200nm 和 500nm 直径的球形颗粒，以及 40×100nm 和 100×400nm 的棒状颗粒（均由 PVP 稳定，在水中和细胞培养基中均分散良好）。从晶体学角度来看，这些颗粒由六方纤锌矿相组成，初级晶粒尺寸为 20 至 100nm。这些颗粒在水中和细胞培养基中（均为中性）的溶解速度较慢（5 天后约为 10%），但在两种不同的模拟溶酶体介质（pH4.5 至 4.8）中约 1 小时内溶解。与呼吸暴露相关的细胞（NR8383 大鼠肺泡巨噬细胞）在体外接触这些颗粒。在体外肺细胞模型中，研究了细胞活力、细胞凋亡和细胞激活（活性氧物种的生成，ROS，细胞因子的释放），并考虑了炎症细胞的迁移。所有颗粒类型都被细胞快速摄取，导致细胞内锌离子浓度增加。与微粒子相比，纳米粒子的细胞毒性更强，与溶解的醋酸锌相当。与溶解的醋酸锌不同，所有颗粒都诱导细胞凋亡，表明这是一种与颗粒有关的机制。微粒子比小颗粒诱导更多的活性氧物种形成，可能是由于微粒子比纳米粒子具有更高的沉降（细胞与颗粒接触）。颗粒类型对细胞因子释放的影响较弱，主要表现为蛋白质微阵列所示的降低。在颗粒诱导的细胞迁移测定（PICMA）中，所有颗粒的作用均低于溶解的醋酸锌。总之，在亚毒性范围内，氧化锌颗粒的生物学效应是由细胞内溶解后释放的锌离子、细胞与颗粒的接触以及氧化锌颗粒被细胞摄取引起的。
