The Impact of Serum Proteins and Surface Chemistry on Magnetic Nanoparticle Colloidal Stability and Cellular Uptake in Breast Cancer Cells.

Superparamagnetic iron oxide nanoparticles (SPIONs) have been extensively studied in biomedical applications for therapeutic or diagnostic purposes. Stability is one of the key determinants dictating successful application of these nanoparticles (NPs) in biological systems. In this study, SPIONs were synthesized and coated with two protective shells-poly(methacrylic acid) (PMAA) or citric acid (CA)-and the stability was evaluated in biologically relevant media together with effect of serum protein supplementation. The stabilities of SPION, SPION-PMAA and SPION-CA in water, DMEM, RPMI, DMEM with 10% (v v^-1), and RPMI with 10% (v v^-1) fetal bovine serum were determined. Without protective shells, the NPs were not stable and formed large aggregates in all media tested. CA improved the stability of the NPs in water, but was not very effective in improving stability in cell culture media. Addition of serum slightly improved colloidal stability of SPION-CA, whereas inclusion of serum significantly improved the colloidal stability of SPION-PMAA. Serum proteins also found to enhance cellular viability of MCF-7 breast cancer cells after exposure to high concentrations of SPION-PMAA and SPION-CA. Different patterns of serum proteins binding to the NPs were observed, and cellular uptake in MCF-7 cells were investigated. The stabilized SPION-PMAA and SPION-CA NPs showed uptake activity with minimal background attachment. Therefore, the importance of colloidal stability of SPIONs for utilizing in future therapeutic or diagnostic purposes is illustrated.