Aptamer-Functionalized Hydrogels for Controlling Protein Release

Protein drugs hold great potential for treating a wide variety of human diseases. However, the efficient and safe delivery of protein drugs in vivo is still a long-standing challenge. Great effort has been made to develop polymeric systems to control the release of protein drugs with desired kinetics. However, current protein delivery systems suffer from problems including the rapid release of protein drugs, the inefficiency of controlling the release of multiple proteins with different release kinetics, and the involvement of toxic molecules and/or harsh conditions during the preparation of protein delivery systems. This Ph.D. project is aimed to create an aptamer-based hydrogel system that is promising to address these problems. The novel hypotheses of this research are: (1) aptamers can bind to and entrap proteins in the hydrogel due to their high affinity and specificity; and (2) the release rate of proteins can be controlled by tuning the binding functionality of aptamers either intramolecularly or intermolecularly. To test these hypotheses and to achieve the goal, two specific tasks have been performed. The first one is to fundamentally understand aptamer-protein interactions at the molecular level. The second one is to thoroughly investigate the effectiveness of using aptamers and molecular triggers to control the release rates of loaded proteins. The results clearly showed that aptamers could be used as novel affinity ligands to functionalize hydrogels for controlling protein release with desired kinetics.