Anna Barbasz

Nanomaterials play a crucial role in various aspects of modern life. Zirconia nanoparticles, extensively employed in medicine for fortifying and stabilizing implants in reconstructive medicine, exhibit unique electrical, thermal, catalytic, sensory, optical, and mechanical properties. While these nanoparticles have shown antibacterial activity, they also exhibit cytotoxic effects on human cells. Our research focuses on understanding how the cells of the human immune system (both the innate response, namely HL-60 and U-937, and the acquired response, namely HUT-78 and COLO-720L) respond to the presence of zirconium (IV) oxide nanoparticles (ZrO2-NPs). Viability tests indicate that ZrO2-NPs exert the highest cytotoxicity on HL-60 > U-937 > HUT-78 > COLO 720L cell lines. Notably, concentrations exceeding 100 μg mL−1 of ZrO2-NPs result in significant cytotoxicity. These nanoparticles readily penetrate the cell membrane, causing mitochondrial damage, and their cytotoxicity is associated with heightened oxidative stress in cells. The use of ZrO2-NP-based materials may pose a risk to immune system cells, the first responders to foreign entities in the body. Biofunctionalizing the surface of ZrO2-NPs could serve as an effective strategy to mitigate cytotoxicity and introduce new properties for biomedical applications.

Human immune cells possess the ability to react complexly and effectively after contact with microbial virulence factors, including those transported in cell-derived structures of nanometer sizes termed extracellular vesicles (EVs). EVs are produced by organisms of all kingdoms, including fungi pathogenic to humans. In this work, the immunomodulatory properties of EVs produced under oxidative stress conditions or at host concentrations of CO2 by the fungal pathogen Candida albicans were investigated. The interaction of EVs with human pro-monocytes of the U-937 cell line was established, and the most notable effect was attributed to oxidative stress-related EVs. The immunomodulatory potential of tested EVs against human THP-1 macrophages was verified using cytotoxicity assay, ROS-production assay, and the measurement of cytokine production. All fungal EVs tested did not show a significant cytotoxic effect on THP-1 cells, although a slight pro-oxidative impact was indicated for EVs released by C. albicans cells grown under oxidative stress. Furthermore, for all tested types of EVs, the pro-inflammatory properties related to increased IL-8 and TNF-α production and decreased IL-10 secretion were demonstrated, with the most significant effect observed for EVs released under oxidative stress conditions.