Cell-biological effects of zinc oxide spheres and rods from the nano- to the microscale at sub-toxic levels
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ORIGINAL ARTICLE
Cell-biological effects of zinc oxide spheres and rods from the nano- to the microscale at sub-toxic levels M. Olejnik & M. Kersting & N. Rosenkranz & K. Loza & M. Breisch & A. Rostek & O. Prymak & L. Schürmeyer & G. Westphal & M. Köller & J. Bünger & M. Epple & C. Sengstock
Received: 10 September 2020 / Accepted: 4 November 2020 # The Author(s) 2020
Abstract 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 2 and 100∙400 nm2 (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 particleinduced 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.
M. Olejnik and M. Kersting Both authors share first authorship. M. Olejnik : K. Loza : A. Rostek : O. Prymak : M. Epple (*) Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CeNIDE), University of Duisburg-Essen, Essen, Germany e-mail: [email protected] M. Kersting : M. Breisch : M. Köller : C. Sengstock (*) Bergmannsheil University Hospital/Surgical Research, Ruhr-University Bochum, Bochum, Germany e-mail: [email protected] N. Rosenkranz : L. Schürmeyer : G. Westphal : J. Bünger Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum (IPA), Bochum, Germany
Keywords Zinc oxide . Nanoparticles . Microparticles . Particle size . Particle shape . Inflammatio
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