The Biological Identity of Nanoparticles

Understanding and controlling the biological response to nanoparticles is essential to designing safe and effective formulations to diagnose and treat disease and for mitigating toxicological risks resulting from incidental or accidental exposure. Because cells are the basic functional units of the body, nanoparticle-cell interactions are a critical determinant of the overall biological response to nanoparticles. In the past, it was assumed that the form of a nanoparticle that comes into contact with cells is the same as the form it had following synthesis. However, when a nanoparticle enters a biological environment, it immediately comes into contact with a complex and highly concentrated mixture of proteins. A subset of these proteins will interact with the surface of a nanoparticle and adsorb to it. The adsorbed proteins form a protein `corona' that defines, in part or in whole, the bioactive interface of a nanoparticle within a biological system. Protein-nanoparticle interactions can also lead to nanoparticle aggregation. The formation of the protein corona and aggregation within a biological environment give the nanoparticle a `biological identity' that is distinct from its `synthetic identity'. It is ultimately the biological identity of a nanoparticle that is `seen' by cells and other components of a biological system and determines the biological response. Yet, it is not clear how the physical and chemical properties of a nanoparticle determine the composition and structure of the protein corona and, in turn, downstream cellular interactions and responses. In this thesis, I elucidate fundamental relationships between nanoparticle design, the composition of the protein corona, and downstream cell interactions within static and dynamic biological environments. These relationships will enable nanoparticle-cell interactions within a biological system to be predicted and controlled and will act as a guide for the design of safer, more effective nanoparticle formulations for nanotechnology applications.