Differential plasma protein binding to metal oxide nanoparticles

Abstract

Nanoparticles rapidly interact with the proteins present in biological fluids, such as blood.The proteins that are adsorbed onto the surface potentially dictate the biokinetics of thenanomaterials and their fate in vivo. Using nanoparticles with different sizes and surfacecharacteristics, studies have reported the effects of physicochemical properties on thecomposition of adsorbed plasma proteins. However, to date, few studies have beenconducted focusing on the nanoparticles that are commonly exposed to the general public,such as the metal oxides. Using previously established ultracentrifugation approaches,two-dimensional gel electrophoresis and mass spectrometry, the current study investigatedthe binding of human plasma proteins to commercially available titanium dioxide,silicon dioxide and zinc oxide nanoparticles. We found that, despite these particleshaving similar surface charges in buffer, they bound different plasma proteins. ForTiO2, the shape of the nanoparticles was also an important determinant of proteinbinding. Agglomeration in water was observed for all of the nanoparticles and bothTiO2 and ZnO further agglomerated in biological media. This led to an increase in the amountand number of different proteins bound to these nanoparticles. Proteins with importantbiological functions were identified, including immunoglobulins, lipoproteins, acute-phaseproteins and proteins involved in complement pathways and coagulation. These resultsprovide important insights into which human plasma proteins bind to particular metaloxide nanoparticles. Because protein absorption to nanoparticles may determine theirinteraction with cells and tissues in vivo, understanding how and why plasma proteins areadsorbed to these particles may be important for understanding their biologicalresponses.