(5cr) Engineering Biomimetic Polymer-Hybrid Delivery Systems

Terry, T. L., University of Massachusetts Amherst

Progress in the fields of molecular biology has elucidated many of the constituent molecules responsible for the progression of various genetic and infectious diseases. These small molecules have been developed into biopharmaceuticals, whose therapeutic efficacy has been substantial limited due to the need for multiple injections. The current approach integrates biopharmaceuticals into synthetic delivery systems whose surface has been modified by polyethylene glycol (PEG) to create a stealth delivery system. PEG primarily functions by preventing protein adsorption via steric stabilization, an inherently passive process, in which, clearance is dependent upon polymer molecular weight and surface heterogeniety. The mechanisms used by cells and pathogens are much more evasive and effective in suppressing phagocytosis. Specific surface receptor-ligand interactions of healthy, native cells protect them from immune clearance. Many of these inhibitory recognition pathway are now known. By mimicking these biological processes, closely, with short peptides utilizing existing signaling pathways to deliver inhibitory singals to immune cells will thereby suppress recognition, inhibiting phagocytosis. The objective is to produce phagocytic-resistant delivery systems through conjugations of "stealth" peptides onto surfaces of synthetic microparticles. Such systems have applications in immunotherapy, biosensors and vaccine delivery, in which, prolonged cellular exposure is needed to create cellular memory.