Design and theoretical studies of magnetite nanoparticles stability in biological media

The use of iron oxide magnetic nanoparticles, in particular magnetite nanoparticles (MNPs), has attracted interest in various biomedical applications. The unavoidable interaction between nanoparticles and biological molecules often affects the aggregation behaviour of nanoparticles. This thesis presents systematic studies of functionalised MNPs through experiments and numerical modelling to understand the aggregation behaviour of MNPs in a biological media. This work shows that the aggregation of MNPs having carboxyl functional groups can be prevented in a RPMI-1640 solution (as a model biological media) containing fetal bovine serum (as a model biological serum) due to the formation of protein corona. Surface-adsorbed proteins serve as a linker that can aid the adsorption of other serum proteins, which otherwise adsorb poorly onto MNPs.Following previous findings, this work also presents an insight into serum protein interaction with MNPs functionalised with linear polymethacrylic acid (20 kDa), linear and branched polyethylenimine (25 kDa), and branched oligoethylenimine (800 Da) that are commonly used for functionalisation of MNPs in many biomedical applications. Different conformations on the surface of MNPs were observed, which in turn affected the interaction of the surface of MNPs with the serum protein. The size stability of MNPs in a RPMI-1640 solution was influenced by the type and amount of protein adsorbed, and the surface conformation of the polymer. A numerical model to study the stability of magnetic nanoparticles in biological media against aggregation with MNPs treated as an aggregate rather than a single, primary nanoparticle was developed. The model showed the key factors that affect stability of MNPs, including the volume fraction of aggregates, absolute zeta potential, thickness of adsorbed steric layer, and conformation of the steric layer on the surface of MNPs; the steric layer can be produced by either polymer or protein coverage. The calculated total interaction potential profiles also revealed that the larger magnetic particles (30 nm diameter) with strong magnetisation (~85 emu/g) always possess a deep secondary minimum due to the strong long range magnetic force. The short range electrostatic and steric repulsive forces, caused by the presence of polyionic and/or protein coatings, could not diminish the secondary minimum to obtain long-term stable MNPs, unless a very thick steric layer of over 100 nm was attained. However, this thick steric layer is not likely to be attained realistically, which explained the difficulty in preventing aggregation of MNP with very strong magnetisation