(313d) Aptamer-Decorated Hydrogels for Sustained Protein Release

Nucleic acid aptamers are a specific type of synthetic ligand. They have high binding affinity and specificity to target proteins. Moreover, they are small, biocompatible, and robust. Thus, they have been widely investigated for various biological and biomedical applications. However, few studies have been pursued to apply nucleic acid aptamers to develop sustained protein release systems. We recently created a novel sustained-release system composed of the aptamers as affinity sites and hydrogel as 3D network. To prove the concept, an aptamer capable of binding platelet-derived growth factor-BB (PDGF-BB) was used as a model. This anti-PDGF-BB aptamer was also modified with either the deletion of essential nucleotides or the addition of non-essential nucleotides to achieve different binding affinity. Mfold algorithm was used to predict the secondary structures of the modified sequences. The binding affinity was experimentally measured using surface plasmon resonance (SPR) and the release kinetics of aptamer-decorated hydrogels was studied through in vitro protein release tests. A mathematical model was also developed to analyze the experimental results. The results showed that approximately 70% of PDGF-BB was released from the native hydrogel during the first day. Differently, the initial release from the highest affinity hydrogel was dramatically decreased to approximately 10 % during the first day and less than 1% per day afterwards. For all other affinity hydrogels, the release profiles were in between the profiles of the native hydrogel and the highest affinity hydrogels. Therefore, the aptamer-decorated hydrogels could be used for the sustained release of PDGF-BB and the desired release kinetics could be achieved by tuning the affinity of the aptamer. This novel affinity hydrogel holds great potential for tissue engineering and drug delivery applications. ---The support from the NSF (DMR-0705716) is gratefully acknowledged---