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 the nanomaterials and their fate in vivo. Using nanoparticles with different sizes and surface characteristics, studies have reported the effects of physicochemical properties on the composition of adsorbed plasma proteins. However, to date, few studies have been conducted 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 investigated the binding of human plasma proteins to commercially available titanium dioxide, silicon dioxide and zinc oxide nanoparticles. We found that, despite these particles having similar surface charges in buffer, they bound different plasma proteins. For TiO2, the shape of the nanoparticles was also an important determinant of protein binding. Agglomeration in water was observed for all of the nanoparticles and both TiO2 and ZnO further agglomerated in biological media. This led to an increase in the amount and number of different proteins bound to these nanoparticles. Proteins with important biological functions were identified, including immunoglobulins, lipoproteins, acute-phase proteins and proteins involved in complement pathways and coagulation. These results provide important insights into which human plasma proteins bind to particular metal oxide nanoparticles. Because protein absorption to nanoparticles may determine their interaction with cells and tissues in vivo, understanding how and why plasma proteins are adsorbed to these particles may be important for understanding their biological responses.

Toxicological Risk Assessment of Emerging Nanomaterials: Cytotoxicity, Cellular Uptake, Effects on Biogenesis and Cell Organelle Activity, Acute Toxicity and Biodistribution of Oxide Nanoparticles

“…Literature regarding the protein corona of TiONts is very limited at present and our group aims to elucidate key aspects of the topic in the years to come. Interestingly, titanate nanotubes bind significantly less plasma proteins than spherical TiO 2 (Degussa P25) [46], even though they display a greater specific surface [2]. These proteins include albumin, Ig heavy chain (mu), Ig light chain, fibrinogen (alpha, beta and gamma chains) and complement C3.…”

The on-bead digestion of protein corona on nanoparticles by trypsin immobilized on the magnetic nanoparticle

“…have been detected in protein coronas on SiO 2 , ZnO, TiO 2 , etc. [24,35], proteins including prenylcysteine oxidase 1, glutathione peroxidase 3, multimerin-1, monocyte differentiation antigen CD14, etc. were found only in the protein corona on the 30 nm Fe 3 O 4 nanoparticles.…”

Two-Dimensional Gel Electrophoresis and Mass Spectrometry in Studies of Nanoparticle-Protein Interactions

“…In a recent study of nanoparticle-plasma protein interactions (Deng et al 2009), the DLS spectra indicated large agglomerates prior to plasma protein exposure. Most likely, and in line with the authors suggestions (Deng et al 2009), complexes with hydrodynamic size of 10000-100 000 nm do not result in the same protein patterns as the interactions of smaller particles/agglomerates and plasma proteins.…”