Cytotoxicity and ER stress-apoptosis gene expression in ZnO nanoparticle exposed THP-1 macrophages: influence of pre-incubation with BSA or palmitic acids complexed to BSA.

In a biological microenvironment, biological macromolecules could interact with nanoparticles (NPs) and consequently influence the toxicity of NPs. This study investigated the effects of BSA or palmitic acids complexed to BSA (PA-BSA) on the toxicity of ZnO NPs to THP-1 macrophages. Atomic force microscopy showed the increase of NP heights after pre-incubation with BSA or PA-BSA, but PA-BSA more effectively altered the hydrodynamic size and zeta potential of NPs. Pre-incubation with BSA but not PA-BSA alleviated ZnO NP induced cytotoxicity, and transmission electron microscopy confirmed fewer intrastructural changes after exposure to ZnO NPs pre-incubated with BSA. ZnO NP exposure increased intracellular Zn ions but decreased reactive oxygen species (ROS) and release of soluble monocyte chemotactic protein-1 (sMCP-1), whereas pre-incubation with BSA and PA-BSA induced a different pattern of intracellular Zn ions and modestly increased intracellular ROS. The expression of ER stress marker DDIT3 was only significantly induced after exposure to NPs pre-incubated with PA-BSA, and CASP12 expression was significantly lower after exposure to NPs pre-incubated with BSA compared to NPs with or without pre-incubation of PA-BSA. In summary, these results showed that pre-incubation with BSA was more effective compared with PA-BSA to alleviate the toxicity of ZnO NPs to THP-1 macrophages, which should be considered for the evaluation of NP toxicity in a biological microenvironment.