A novel and rapid method for quantification of magnetic nanoparticle--cell interactions using a desktop susceptometer

摘要

Activated endothelial cells (EC) are attractive prime targets for specific drug delivery using drug-carrying magnetic nanoparticles. In order to accomplish EC targeting, the interaction between magnetic particles and resting as well as activated endothelial cells must be characterized and quantified, because it will influence particle biodistribution, circulation half-time, and targeting efficacy. Here, we have quantified in vitro the interaction (adhesion/phagocytosis) between human endothelial cells and magnetite (Fe_3O_4) particles carrying different surface coatings with varying degrees of hydrophilicity and surface charge. Almost no adhesion was observed (about 1 percent or less) for three out of five particle types carrying plain dextran, carboxyl-substituted poly(ethylene glycol) and silica C18 coatings. In contrast, carboxyl-functionalized dextran and poly(ethylene glycol)-coated particles adhered or were phagocytosed to a considerable degree (58 and 26 percent, respectively). These clear and accurate results were obtained by measuring the magnetic response, i.e. magnetic susceptibility, from different fractions of the cell cultures as a means of determining the concentration of magnetic particles. Visible light and electron microscopy confirmed the magnetic quantification. To meet the need for a rapid yet sensitive instrument, we have developed a desktop magnetic susceptometer especially adapted for liquid samples or particles in a suspension. Despite its very high sensitivity, it is easy to operate and requires but a few seconds for a measurement. We also describe the construction and operation of this instrument.