Tissue and cell-specific drug targeting can be achieved by employing nanoparticle coatings or carrier-drug conjugates that contain a ligand recognized by a receptor on the target cell. Superparamagnetic iron oxide nanoparticles have been used for many years in various biomedical applications. In this study, superparamagnetic nanoparticles with specific shape and size have been prepared and coupled to various proteins. These particles are characterized in vitro and their influence on human dermal fibroblasts is assessed in terms of cell adhesion, viability, morphology and cytoskeleton organization using various techniques to observe cell-nanoparticle interaction, including light, fluorescence, scanning and transmission electron microscopy. The results showed that each nanoparticle type with different surface characteristics caused a distinctly different cell response. The underivatized magnetic particles were internalized by the fibroblasts probably due to endocytosis, which resulted in disruption of the cell membrane and disorganized cell cytoskeleton. In contradiction, lactoferrin or ceruloplasmin coated nanoparticles attached to the cell membrane, most likely to the cell expressed receptors and were not endocytosed. One major problem with uncoated magnetic nanoparticles has been the endocytosis of particles leading to irreversible entry. These experiments provide a route to prevent this problem, suggesting that cell response can be directed via specifically engineered particle surfaces.