Tuning the Protein Corona of Polymer Nanoparticle Hydrogels

Subjecting a nanoparticle to a complex biological mixture results in a near instantaneous protein adsorption event. The type and quantity of protein adsorbed is termed the protein corona. The synthetic identity of a nanoparticle is perhaps the most important determining factor in the protein corona composition. However, the relationship between synthetic identity and the protein corona is complicated by multiple variables which makes rational nanoparticle optimization a challenge and favors high-throughput screens of nanoparticle compositions in order to optimize and tune the protein corona. In chapter one, a number of examples of tuning the protein corona by changing the synthetic composition of a nanoparticle are presented. Additionally, other factors influencing the protein corona of a nanoparticle are discussed including pH and temperature. In chapter two, a systematic study analyzing the effect of cross-linking in a nanoparticle is discussed. Information from this study played an important role in the protein corona optimization of a toxin-sequestering nanoparticle in chapter three. This nanoparticle, with a demonstrated ability to selectively sequester and neutralize diverse toxins found in snake venom, is shown to inhibit venom-induced dermonecrosis in chapter four. Using a quartz crystal microbalance in chapter five to analyze the relative affinity of toxin isoforms to the venom-binding nanoparticle, it is shown that the nanoparticle interacts with toxins through diverse mechanisms. The complex stoichiometry between a nanoparticle and a protein complicates the analysis of binding event making comparisons between Langmuir derived disassociation constants inadequate. Finally, in chapter six, a high-throughput analytical technique using a modified version of equilibrium dialysis is presented. This solution-based method of studying capacity and affinity of a nanoparticle of a biomacromolecule is amenable to automation and has the potential to accelerate the largely empirical optimization process used to tune the protein corona