Interaction of Anionic Superparamagnetic Nanoparticles with Cells: Kinetic Analyses of Membrane Adsorption and Subsequent Internalization

Abstract

Cell targeting with magnetic nanoparticles raises a growing interest in the fields of both cellular biology and medical imaging. We have investigated the nonspecific interactions of superparamagnetic negatively charged iron oxide nanoparticles with HeLa tumor cells and mouse RAW macrophages, qualitatively by electron microscopy and quantitatively following the particle cell uptake by two magnetic based quantification assays (magnetophoresis and electron spin resonance). The analyses of particle uptake kinetics at 4 and 37 °C led us to modelize the observed endocytosis as a two-step process: we distinguish the binding of anionic magnetic nanoparticles onto the cell surface (described as a Langmuir adsorption) from the subsequent step of cell internalization (also described as a saturable mechanism). Fits of experimental uptake kinetics result in the quantitative determination of binding parameters (adsorption rate, desorption rate, and density of binding sites) as well as internalization rate and internalization capacity. All binding parameters appear to coincide for tumor cells and macrophages, whereas their internalization capacity differs by 1 order of magnitude, reflecting the cell function specificity.