Abstract:
Nanocarriers have been studied widely owing to their promising features in the field of drug delivery and they improve pharmacokinetic properties, biodistribution, solubility and stability, provide controlled release and site-specific delivery of the therapeutic agents, and decrease the toxicology at the targeted site. Also, the nanocarriers exhibit unique physiochemical properties by the opportunity of changing their sizes, compositions, shapes and surface properties. The present study involves a combined approach of the characterization of the polystyrene latex nanoparticles (PSL NPs), DOPC liposomes and hybrid NPs (DOPC encapsulated PSL NPs) having different concentrations, sizes, surface charges and functional groups and the determination of their cytotoxicity effects towards the Sac6:RFP tagged S. cerevisiae cells as well as the investigation of the possible uptake mechanisms of the PSL NPs. DLS, ELS, STEM and TEM analyses were carried out to characterize the nanoparticles. CFU analysis and CLSM imaging were performed to determine the toxicity of the nanoparticles. Negatively charged PSL NPs do not show toxicity at 50 mg/L, while the concentration increase results in viability decrease, such that at 800 mg/L, the viability percentage of the cells is around 60%. 30nm-C-n PSL NPs are internalized by the cells and show toxic effect if they enter to the nucleus. 50nm-A-p and 100nm-A-p PSL NPs are non-toxic at 50 mg/L, but they are fully toxic after 100 mg/L concentration. They cover the cell surface and inhibit the cell viability. Hybrid nanoparticles exhibit opposite viability results compared to their PSL NP counterparts. The long-term toxicity effect study reveals that negatively charged and carboxyl functionalized PSL NPs at 100-200 mg/L concentrations do not show toxicity after 15 generations of NP exposure. Endocytosis inhibitor treatment experiments show that the PSL NPs are internalized by diffusion, partly microtubule dependent or a different factor mediated endocytosis.
