The Toxicity of Polystyrene-Based Nanoparticles in Saccharomyces cerevisiae Is Associated with Nanoparticle Charge and Uptake Mechanism

Polystyrene latex (PSL) nanoparticles (NPs), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes, and hybrid NPs that have different concentrations, sizes, surface charges, and functional groups were used to determine their toxicity to Saccharomyces cerevisiae cells. The size, charge, and morphology of the nanoparticles were characterized by dynamic light scattering, electrophoretic light scattering, scanning transmission electron microscopy, and transmission electron microscopy analysis. The cell viabilities were determined by colony forming unit analysis and confocal laser scanning microscopy imaging. Uptake inhibition studies were performed to determine the internalization mechanism of PSL NPs. At 50 mg/L, both positively and negatively charged NPs were slightly toxic. With increasing concentration, however, full toxicities were observed with positively charged PSL NPs, while a marginal increase in toxicity was obtained with negatively charged PSL NPs. For negatively charged and carboxyl-functionalized NPs, an increase in size induced toxicity, whereas for positively charged and amine-functionalized NPs, smaller-sized NPs were more toxic to yeast cells. Negatively charged NPs were internalized by the yeast cells, but they showed toxicity when they entered the cell vacuole. Positively charged NPs, however, accumulated on the cell surface and caused toxicity. When coated with DOPC liposomes, positively charged NPs became significantly less toxic. We attribute this reduction to the larger-diameter and/or more-agglomerated NPs in the extracellular environment, which resulted in lower interactions with the cell. In addition to endocytosis, it is possible that the negatively charged NPs (30-C-n) were internalized by the cells, partly via direct permeation, which is preferred for high drug delivery efficiency. Negatively charged PSL NP exposure to the yeast cells at low-to-moderate concentrations resulted in low toxicities in the long term. Our results indicate that negatively charged PSL NPs provide safer alternatives as cargo carriers in drug delivery applications. Moreover, the variations in NP size, concentration, and exposure time, along with the use of hybrid systems, have significant roles in nanoparticle-based drug delivery applications in terms of their effects on living organisms.