Characterization of Protein Clusters of Diverse Magnetic Nanoparticles and Their Dynamic Interactions with Human Cells

Although nanoparticle/protein binding and the cytotoxicity of nanoparticles have been separately reported, there has been no study linking the nature of nanoparticle/protein clusters to cell uptake and the dynamic cellular responses. We report here that water-soluble iron oxide-based magnetic nanoparticles (MNPs) with different sizes and surface chemistry bind different serum proteins in terms of protein identity and quantity without changing the protein secondary structures. Carboxylated MNPs (and aminated one in smaller MNPs) resulted in higher cytotoxicity, and PEG coating reduced both cell uptake and the cytotoxicity. Smaller MNPs (especially the carboxylated one) bind more serum proteins, are much less taken up by cells as compared to larger particles, and yet elicit more dynamic cytotoxic responses. Besides the intrinsic effects of size and surface charge of the water-soluble MNPs, the cellular effects of MNPs/protein clusters were also attributed to the identity and quantity of the adsorbed proteins rather than the binding-induced new epitopes on the proteins.