(611g) Pathology Driven Approaches to Polymeric Drug Delivery to the Brain (Invited Speaker)

Current techniques of neurodegenerative disease detection involve lysing cell populations or analyzing post-mortem tissue; these techniques create a significant bottleneck in obtaining information about cellular characteristics of neurodegeneration because they do not adequately preserve information on disease progression. Although, all neurodegenerative disorders involve lysosomal dysfunction and storage products, the pathway by which accumulation leads to neurodegeneration can vary patient to patient. Therefore, we are filling a critical need to perform mechanistic studies into the temporospatial behavior of neurodegenerative pathways in live cells, with the goal of correlating known cellular changes in neurodegeneration to identifiable and measurable increases in lysosomal hydrolase activity in real time to allow for personalized disease analysis. Cellular information gained is used in the development of enzyme-responsive polymersomes to be used as simultaneous diagnostic and therapeutic tools in brains of patients. These nanoparticles respond to enzyme upregulation, releasing both a diagnostic signal and a therapeutic enzyme for treatment.