Effects of Zn–ZnO Core–Shell Nanoparticles on Antimicrobial Mechanisms and Immune Cell Activation

[Image: see text] The deposition of zinc–zinc oxide nanoparticles (Zn–ZnO NPs) onto porous Ta(2)O(5) surfaces enriched with calcium phosphate by DC magnetron sputtering was investigated to improve the surface antimicrobial activity without triggering an inflammatory response. Different sizes and amounts of Zn NPs obtained by two optimized different depositions and an additional thin carbon (C) layer deposited over the NPs were explored. The deposition of the Zn NPs and the C layer mitigates the surface porosity, increasing the surface hydrophobicity and decreasing the surface roughness. The possible antimicrobial effect and immune system activation of Zn–ZnO NPs were investigated in Candida albicans and macrophage cells, respectively. It was found that the developed surfaces displayed a fungistatic behavior, as they impair the growth of C. albicans between 5 and 24 h of culture. This behavior was more evident on the surfaces with bigger NPs and the highest amounts of Zn. The same trend was observed in both reactive oxygen species (ROS) generation and loss of C. albicans’ membrane integrity. After 24 h of culture, cell toxicity was also dependent on the amount of the NPs. Cell toxicity was observed in surfaces with the highest amount of Zn NPs and with the C layer, while cells were able to grow without any signs of cytotoxicity in the porous surfaces with the lowest amount of NPs. The same Zn-dose-dependent behavior was noticed in the TNF-α production. The Zn-containing surfaces show a vastly inferior cytokine secretion than the lipopolysaccharide (LPS)-stimulated cells, indicating that the modified surfaces do not induce an inflammatory response from macrophage cells. This study provides insights for understanding the Zn amount threshold that allows a simultaneous inhibition of the fungi growth with no toxic effect and the main antimicrobial mechanisms of Zn–ZnO NPs, contributing to future clinical applications.