The role of nanomaterial-protein interactions in determining the toxic consequences of nanomaterial exposure

Abstract

As early biological responses to foreign objects in the body can be influenced by their bound proteins, the nanomaterial hard protein corona (the collection of slow exchange proteins that associate with nanomaterials) is an emerging area of interest in nanotoxicology. There is a limited but growing appreciation of the role these interactions have in influencing nanomaterial toxicity. This research dealt with (i) the characterisation of iron oxide and silica particles with and without a plasma, serum and lung lining fluid protein hard corona, (ii) the identification of the proteins in the hard corona that associate with the particles and (iii) the effect of the hard corona on influencing particle cytotoxicity in a J774.A1 macrophage cell line. Initial investigation of the particles illustrates the advantages in using a variety of characterisation techniques to better elucidate particle properties. Subsequent characterisation of the hard corona protein profile demonstrated a clear difference in the biological identity of the particles in a plasma, serum and in a lung lining fluid corona. Although it is difficult to associate the impact of any individual protein identified in the hard corona to cytotoxicity this study indicates that the binding of proteins plays a significant role in altering the cytotoxic potential (as determined by LDH release) in macrophages. The work also demonstrates the hard corona has an impact on macrophage chemotaxis, which further strengthens the hypothesis that the corona is a key consideration in nanoparticle toxicity. Ultimately this thesis finds that the nanomaterial hard corona is an important element to consider in experimental design and highlights the concept of creating particle preparation protocols to mimic the corona composition in vivo when examining in vitro cellular responses. This research highlights the implications for interpretation of data from in vitro cell culture tests that do not take the protein corona into consideration.