Fe₃O₄Nanoparticle-protein Interactions And Their Biological Effects

As a special type of functional magnetic nanomaterials, Fe3O4nanoparticlesexhibit broad application in the field of biomedical imaging, tumor targeting,magnetic separation, magnetic resonance imaging (MRI), thermal therapy and drugdelivery. Therefore, the biocompatibility of Fe3O4nanoparticles have beenincreasingly concerned. Once entering the body, nanoparticles are able to interactwith abundant protein molecules in the life system, mainly due to their small scale,high surface area and strong absorption ability. As a result, the so-called "ProteinCorona" would be formed via the absorption of proteins on the nanoparticles. Proteincorona would influence the biological effects of nanoparticles, such as cellularuptake, biocompatibility or pharmacokinetics. Accordingly, in order to assess thebiocompatibility of Fe3O4nanoparticles, the interaction between Fe3O4nanoparticlesand proteins in life system should be understood in the first place. In this article, wefirst investigated the interactions between Fe3O4nanoparticles (~5nm) and threetypes of model proteins, then we analyzed the effects of particle size and modelprotein type on the interaction of Fe3O4with model proteins. Finally, the effects ofFe3O4nanoparticle-protein complexes on cell autophagy were measured. Thedetailed contents were as following:Firstly, Fe3O4nanoparticles (~5nm) were used as the subject of our study. Theinteraction between Fe3O4nanoparticles and albumin, fibrin and immunoglobulinwas studied. The cellular uptake and biocompatibility of nanoparticle-proteincomplex were also investigated. Results have shown that nanoparticles were able toabsorb all three kinds of proteins, and the absorption amounts would differ mainlydepending on the types of protein: Fibrin> immunoglobulin> albumin. Theas-formed Fe3O4nanoparticle-protein complex could significantly decrease thetoxicity of naked nanoparticles. Moreover, the degree of toxicity attenuation wascorrelative with the absorption amounts of proteins on Fe3O4nanoparticlesSecondly, we studied the interaction between three kinds of Fe3O4nanoparticles(5,10and20nm) and a series of model proteins (albumin, fibrin, immunoglobulinand transferrin). Results suggested that particle size effects would greatly affect theabsorption of proteins on the nanoparticles. The nanoparticles with larger diameterwould adsorb more proteins. Meanwhile, the protein types proved to be another influential factor of the mutual interactions. The absorption abilities of Fe3O4nanoparticles with three diameters for proteins from high to low were as follows:fibrin> immunoglobulin> transferrin> albumin.Finally, we have prepared five different Fe3O4nanoparticle-protein complexes,including Fe3O4nanoparticle-FBS complexes, Fe3O4nanoparticle-BSA complexes,Fe3O4nanoparticle-BTf complexes, Fe3O4nanoparticle-BIg complexes and Fe3O4nanoparticle-BFg complexes, then investigated the influence of protein corona oncell autophagy induced by Fe3O4nanoparticles. Results showed that Fe3O4nanoparticle-protein complexes could regulate cell autophagy, and the regulationability was closely related to protein types.In conclusion, through the above studies, we have comprehensivelydemonstrated the impact of particle size effect and protein types on the interactionsbetween Fe3O4nanoparticles and proteins. Moreover, the influence of Fe3O4nanoparticle-protein nanocomplexes on nanoparticle biocompatibility, cellularuptake, and cell autophagy has been elaborated. Finally, we summarized this project,and proposed an outlook and the next working plan.