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.