Department of Chemical, Materials, and Biomolecular Engineering, University of Connecticut, Storrs, CT 06269-3222, USA.
Biomacromolecules. 2010 Oct 11;11(10):2724-30. doi: 10.1021/bm100774t.
Various in situ injectable hydrogels have been developed for protein delivery in treating human diseases. However, most hydrogels are highly permeable, which can lead to the rapid release of loaded proteins. The purpose of this study is to apply nucleic acid aptamers to functionalize an in situ injectable hydrogel model to control the release of proteins. The aptamers were studied using secondary structural predictions and binding analyses. The results showed that the structural predictions were different from the experimental measurements in numerous cases. The affinity of the aptamer was significantly affected by the mutations of the essential nucleotides, whereas it was not significantly affected by the variations of the nonessential nucleotides. The mutated aptamers were then used to functionalize the injectable hydrogel model. The results showed that the aptamer-functionalized hydrogel could prolong protein release. Moreover, the release rates could be controlled by adjusting the affinity of the aptamer.
各种原位可注射水凝胶已被开发用于治疗人类疾病的蛋白质输送。然而，大多数水凝胶具有高渗透性，这可能导致负载蛋白质的快速释放。本研究的目的是应用核酸适体来对原位可注射水凝胶模型进行功能化，以控制蛋白质的释放。使用二级结构预测和结合分析研究了适体。结果表明，在许多情况下，结构预测与实验测量结果不同。适体的亲和力受必需核苷酸突变的显著影响，而非必需核苷酸的变化则对亲和力影响不大。然后将突变的适体用于功能化可注射水凝胶模型。结果表明，适体功能化的水凝胶可以延长蛋白质的释放。此外，可以通过调整适体的亲和力来控制释放速率。
