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

Abstract

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.

Cytotoxicity of nickel zinc ferrite nanoparticles on cancer cells of epithelial origin

“…The magnetic nanoparticles are rapidly distributed in epithelial tissue with strong binding to plasma proteins, principally albumin. 30 Activation of endogenous nuclease enzymes is considered to be a key biochemical event in apoptosis, leading to the cleavage of DNA into nucleosomesized fragments, and it is well-known that caspase-3 is a key mediator of nuclease activation. 31 The three cell lines, HT29, MCF7, and HepG2, were treated with increasing concentrations of NiZn ferrite nanoparticles to determine conditions that could induce apoptosis as measured by a standard interchromosomal DNA fragmentation assay.…”

Modulatory Effect of Citrate Reduced Gold and Biosynthesized Silver Nanoparticles on α-Amylase Activity

“…Therefore, the composition of the protein corona largely defines the biological identity of the nanoparticle. In addition, because of their extremely large surface area to volume ratios, a significant number of proteins can be adsorbed and "trapped" on AuNPs surfaces when they are introduced into biological entities [22][23][24][25][26][27]. Gold nanoparticles present an alternate and advantageous synthetic scaffold for targeting protein surfaces [28] and have been demonstrated to bind biomacromolecules, [29] facilitate DNA transfection [30], and reversibly inhibit enzymes [31].…”

Biomolecular coronas provide the biological identity of nanosized materials

“…Systematic and good quality information on the composition of the hard corona is now emerging, both in terms of identities 13 It should be noted that most current methods to determine the corona composition first separate all of the strongly adsorbed biomolecules from the particles into a single biomolecule sample, and then use mass spectrometry to identify the recovered proteins or other components. However, because the corona is not at thermodynamic equilibrium, there could be statistical fluctuations in its composition and organization from particle to particle within the same sample 8,87 . Besides emphasizing that most of the hard corona is composed of few proteins, Table 1 suggests that there are many more proteins in the average corona than what would fit on one particle surface.…”