Department of Chemical, Materials & Biomolecular Engineering, University of Connecticut, Storrs, CT 06269-3222, USA.
Biomaterials. 2011 Oct;32(28):6839-49. doi: 10.1016/j.biomaterials.2011.05.074. Epub 2011 Jun 17.
Biomaterials for the precise control of protein release are important to the development of new strategies for treating human diseases. This study aimed to fundamentally understand aptamer--protein dissociation triggered by complementary oligonucleotides, and to apply this understanding to develop affinity hydrogels for controlled protein release. The results showed that the oligonucleotide tails of the aptamers played a critical role in inducing intermolecular hybridization and triggering aptamer--protein dissociation. In addition, the attachment of the oligonucleotide tails to the aptamers and the increase of hybridizing length could produce a synergistic effect on the dissociation of bound proteins from their aptamers. More importantly, pegylated complementary oligonucleotides could successfully trigger protein release from the aptamer-functionalized hydrogels at multiple time points. Based on these results, it is believed that aptamer-functionalized hydrogels and complementary oligonucleotides hold great potential of controlling the release of protein drugs to treat human diseases.
用于精确控制蛋白质释放的生物材料对于开发治疗人类疾病的新策略非常重要。本研究旨在从根本上理解适体-蛋白质解偶联是如何被互补寡核苷酸触发的,并将这一理解应用于开发用于控制蛋白质释放的亲和水凝胶。结果表明,适体的寡核苷酸尾巴在诱导分子间杂交和触发适体-蛋白质解偶联方面起着关键作用。此外,寡核苷酸尾巴与适体的连接以及杂交长度的增加,可以对结合蛋白从适体上的解离产生协同效应。更重要的是,聚乙二醇化的互补寡核苷酸可以成功地从适体功能化水凝胶中在多个时间点触发蛋白质释放。基于这些结果,可以相信适体功能化水凝胶和互补寡核苷酸在控制蛋白质药物释放以治疗人类疾病方面具有巨大的潜力。