Updated project metadata. We determined the composition of the plasma protein corona on silica-coated versus dextran-coated iron oxide nanoparticles using mass spectrometry-based proteomics approaches. Gene ontology (GO) enrichment analysis and Ingenuity Pathway Analysis (IPA) revealed distinct protein corona compositions for the two different SPIONs. Relaxivity of silica-coated SPIONs was modulated by the presence of a protein corona. Moreover, the viability of primary human monocyte-derived macrophages was influenced by the protein corona on silica-coated, but not dextran-coated SPIONs, and the protein corona promoted cellular uptake of silica-coated SPIONs, but did not affect internalization of dextran-coated SPIONs.