Carboxylated superparamagnetic iron oxide particles label cells intracellularly without transfection agents

Cell labeling by superparamagnetic iron oxide particles (SPIO) has emerged as a potentially powerful tool to monitor trafficking of transplanted cells by magnetic resonance tomography, e.g., in studies for tissue repair. However, intracellular labeling is mostly achieved by transfection agents not approved for clinical use. In this work, the feasibility and efficiency of labeling human mesenchymal stem cells (MSC) and HeLa cells with two commercially available SPIOs (Resovist® and Feridex®) without transfection agents was evaluated. In both cell types, Resovist® without a transfection agent was more efficiently taken up than Feridex®. Increasing the concentration of Resovist® can yield similar amounts of iron in cells as SPIOs with transfection agents. This offers the opportunity to omit transfection agents from the labeling protocol when Resovist® is used. Intracellular localization of the contrast agents is found by light microscopy and confirmed by electron microscopy. Coagulation of the SPIO nanoparticles, which is problematic for the quantification of the intracellular iron content, was observed and analyzed with a fluorescent activated cell sorter. As Resovist® consists of a carboxydextran shell in contrast to Feridex® which is composed of a dextran shell, we synthesized fluorescent polymeric nanoparticles as model systems with different amounts of carboxyl groups on the surface by the miniemulsion process. A steady increase in uptake of nanoparticles was detected with a higher density of carboxyl groups showing the relevance of charged groups as in the case of Resovist®. Aggregation of these polymeric nanoparticles was not found.