Serum albumin corona on ZnO NPs has opposite effect in cellular and mitochondrial toxicity experimental models

Abstract

Zinc oxide nanoparticles (ZnO NPs) are increasingly applied in a diverse array of industrial and commercial products. In the biological milieu a protein corona is formed on the surface of NPs. The protein corona changes the mode of NPs interaction with cells, organelles and molecules resulting in a different biological effect of NPs as compared to plain NPs. Bovine serum albumin (BSA) and zinc oxide nanoparticles (ZnO NPs) were chosen in this study as a model system to investigate NPs-protein corona complex toxicity to cells and isolated mitochondria. In the cellular experimental model plain 20 nm ZnO NPs (ZnO) and ZnO NPs coated with bovine serum albumin (ZnO-BSA) were tested for citotoxicity and ROS generation in rabbit myoblast (Fr2) and human breast carcinoma (MX-1) cell lines. Both NPs types were cytotoxic with similar dependency on concentration, however, NPs were appr. 10% less toxic to Fr2 at high concentration (200 μg/ml) as compared to MX-1 and ZnO-BSAwere less toxic than ZnO NPs in the concentration range of 150-200 μg/ml. ZnO-BSA NPs haven’t induced ROS generation in none of cell line. The minimum ZnO concentration that induced ROS generation in MX-1 was lower as compared to Fr2 – 20 and 50 μg/ml, respectively. The treatment of mitochondria with ZnO NPs had an unexpected effect: ZnO-BSA NPs impaired stronger the mitochondrial respiration in metabolic state 3 and uncoupled state and induced more pronounced mitochondrial swelling than ZnO NPs meaning the opening of the permeability transition pore. ZnO-BSA NPs inhibited state 3 respiration rate by 50% at the concentration of 0.25 μg/ml, whereas ZnO NPs – at 0.40 μg/ml. Moreover, the site of inhibition in oxidative phosphorylation system was different for plain and BSA-coated NPs: the main effect of ZnO NPs was on phosphorylation subsystem whereas the main effect of ZnO-BSA NPs was on respiratory subsystem. [...]