The Biokinetics and Toxicology of Fe3O4 Nanoparticles Influenced by Magnetic Field and Protein

Magnetic nanoparticles (MNPs) used in bio-application have accelerated the development of "theranostics" which contains imaging, therapy and drug delivery. However, in a protein-rich physiological fluid, MNPs are ineluctable to a contact with protein to form "protein corona", which will significantly change the physicochemical properties of the particles and their biological behavior. Therefore, we investigated the influence of protein and static magnetic field (SMF) on the cytotoxicity and cellular uptake of MNPs. The Fe3O4 nanoparticles (Fe3O4 NPs) were synthesized by solvothermal method with a mean diameter of similar to 100nm functionalized with carboxyl groups. After a period of 12h incubation in complete medium (CM), the wrapping of the Fe3O4 NPs by protein adsorption resulted in about 40-nm increase of the hydrodynamic size. Their stability in CM and water solution did not broaden significantly over time, which is exactly opposite in serum-free media (SFM). When transferred to SFM with high ionic-strength, the Fe3O4 NPs aggregated and settled quickly. We explore that the cell viability was decreased in proportion to the concentration and incubating time of Fe3O4 NPs, the absence of FBS and the presence of SMF exposure, respectively. Quantitative analysis showed that cells could incorporate more NPs in SFM, about five-fold more than in CM. In addition, it is obvious that exposure to SMF resulted in more cellular uptake both in CM and SFM. Our results demonstrated that Fe3O4 NPs in SFM and SMF exposure would settle down to cell rapidly, which caused more cellular uptake and higher cytotoxicity.