Nanomagnetic sensing of blood plasma protein interactions with iron oxide nanoparticles: impact on macrophage uptake.

One of the first biointeractions of magnetic nanoparticles with living systems is characterized by nanoparticle-protein complex formation. The proteins dynamically encompass the particles in the protein corona. Here we propose a method based on nanomagnetism that allows a specific in situ monitoring of interactions between iron oxide nanoparticles and blood plasma. Tracking the nanoparticle 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 nanoparticles and assesses eventual onset of particle aggregation. Since some of the plasma proteins may cause particle aggregation, we use magnetic fractionation to separate the nanoparticle clusters (induced by "destabilizing proteins") from well-dispersed nanoparticles, 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 (clustered versus isolated) of nanoparticles 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/nanoparticle 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 nanoparticle/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.

Size-sorted anionic iron oxide nanomagnets as colloidal mediators for magnetic hyperthermia.

Iron oxide colloidal nanomagnets generate heat when subjected to an alternating magnetic field. Their heating power, governed by the mechanisms of magnetic energy dissipation for single-domain particles (Brown and Néel relaxations), is highly sensitive to the crystal size, the material, and the solvent properties. This study was designed to distinguish between the contributions of Néel and Brownian mechanisms to heat generation. Anionic nanocrystals of maghemite and cobalt ferrite, differing by their magnetic anisotropy, were chemically synthesized and dispersed in an aqueous suspension by electrostatic stabilization. The particles were size-sorted by successive electrostatic phase separation steps. Parameters governing the efficiency of nanomagnets as heat mediators were varied independently; these comprised the particle size (from 5 to 16.5 nm), the solvent viscosity, magnetic anisotropy, and the magnetic field frequency and amplitude. The measured specific loss powers (SLPs) were in quantitative agreement with the results of a predictive model taking into account both Néel and Brown loss processes and the whole particle size distribution. By varying the carrier fluid viscosity, we found that Brownian friction within the carrier fluid was the main contributor to the heating power of cobalt ferrite particles. In contrast, Néel internal rotation of the magnetic moment accounted for most of the loss power of maghemite particles. Specific loss powers were varied by 3 orders of magnitude with increasing maghemite crystal size (from 4 to 1650 W/g at 700 kHz and 24.8 kA/m). This comprehensive parametric study provides the groundwork for the use of anionic colloidal nanocrystals to generate magnetically induced hyperthermia in various media, including complex systems and biological materials.