Nanomagnetic Sensing of Blood Plasma Protein Interactions with Iron Oxide Nanoparticles: Impact on Macrophage Uptake

One of the first biointeractions of magnetic nanopartides with living systems is characterized by nanopartide-protein complex formation. The proteins dynamically encompass the partides in the protein corona. Here we propose a method based on nanomagnetism that allows a specific in situ monitoring of interactions between iron oxide nanopartides and blood plasma. Tracking the nanopartide orientation through their optical birefringence signal induced by an external magnetic field provides a quantitative real-time detection of protein corona at the surface of nanopartides and assesses eventual onset of particle aggregation. Since some of the plasma proteins may cause particle aggregation, we use magnetic fractionation to separate the nanopartide dusters (induced by destabilizing proteins) from well-dispersed nanopartides, which remain isolated due to a stabilizing corona involving other different types of proteins. Our study shows that the biological identity' (obtained after the particles have interacted with proteins) and aggregation state (dustered versus isolated) of nanopartides depend not only on their initial surface coating, but also on the concentration of plasma in the suspension. Low plasma concentrations (which are generally used in vitro) lead to different protein/nanopartide complexes than pure plasma, which reflects the in vivo conditions. As a consequence, by mimicking in vivo conditions, we show that macrophages can perceive several different populations of nanopartide/protein complexes (differing in physical state and in nature of associated proteins) and uptake them to a different extent. When extrapolated to what would happen in vivo, our results suggest a range of cell responses to a variety of nanoparticle/protein complexes which circulate in the body, thereby impacting their tissue distribution and their efficiency and safety for diagnostic and therapeutic use.