Institute for Biomaterials, Drug Delivery, and Regenerative Medicine, C0800, The University of Texas at Austin , Austin, Texas 78712, United States.
Department of Biomedical Engineering, C0800, The University of Texas at Austin , Austin, Texas 78712, United States.
Acc Chem Res. 2017 Feb 21;50(2):170-178. doi: 10.1021/acs.accounts.6b00533. Epub 2017 Feb 7.
Nature has mastered the art of molecular recognition. For example, using synergistic non-covalent interactions, proteins can distinguish between molecules and bind a partner with incredible affinity and specificity. Scientists have developed, and continue to develop, techniques to investigate and better understand molecular recognition. As a consequence, analyte-responsive hydrogels that mimic these recognitive processes have emerged as a class of intelligent materials. These materials are unique not only in the type of analyte to which they respond but also in how molecular recognition is achieved and how the hydrogel responds to the analyte. Traditional intelligent hydrogels can respond to environmental cues such as pH, temperature, and ionic strength. The functional monomers used to make these hydrogels can be varied to achieve responsive behavior. For analyte-responsive hydrogels, molecular recognition can also be achieved by incorporating biomolecules with inherent molecular recognition properties (e.g., nucleic acids, peptides, enzymes, etc.) into the polymer network. Furthermore, in addition to typical swelling/syneresis responses, these materials exhibit unique responsive behaviors, such as gel assembly or disassembly, upon interaction with the target analyte. With the diverse tools available for molecular recognition and the ability to generate unique responsive behaviors, analyte-responsive hydrogels have found great utility in a wide range of applications. In this Account, we discuss strategies for making four different classes of analyte-responsive hydrogels, specifically, non-imprinted, molecularly imprinted, biomolecule-containing, and enzymatically responsive hydrogels. Then we explore how these materials have been incorporated into sensors and drug delivery systems, highlighting examples that demonstrate the versatility of these materials. For example, in addition to the molecular recognition properties of analyte-responsive hydrogels, the physicochemical changes that are induced upon analyte binding can be exploited to generate a detectable signal for sensing applications. As research in this area has grown, a number of creative approaches for improving the selectivity and sensitivity (i.e., detection limit) of these sensors have emerged. For applications in drug delivery systems, therapeutic release can be triggered by competitive molecular interactions or physicochemical changes in the network. Additionally, including degradable units within the network can enable sustained and responsive therapeutic release. Several exciting examples exploiting the analyte-responsive behavior of hydrogels for the treatment of cancer, diabetes, and irritable bowel syndrome are discussed in detail. We expect that creative and combinatorial approaches used in the design of analyte-responsive hydrogels will continue to yield materials with great potential in the fields of sensing and drug delivery.
大自然已经掌握了分子识别的艺术。例如，利用协同的非共价相互作用，蛋白质可以区分分子并以难以置信的亲和力和特异性结合伴侣。科学家们已经开发并继续开发技术来研究和更好地理解分子识别。因此，模拟这些识别过程的对分析物响应的水凝胶已经成为一类智能材料。这些材料不仅在它们响应的分析物类型上是独特的，而且在实现分子识别的方式以及水凝胶对分析物的响应方式上也是独特的。传统的智能水凝胶可以响应 pH 值、温度和离子强度等环境线索。用于制造这些水凝胶的功能单体可以变化以实现响应行为。对于对分析物响应的水凝胶，通过将具有固有分子识别特性的生物分子（例如核酸、肽、酶等）掺入聚合物网络中，也可以实现分子识别。此外，除了典型的溶胀/收缩响应外，这些材料在与目标分析物相互作用时还表现出独特的响应行为，例如凝胶组装或解组装。由于具有用于分子识别的各种工具以及生成独特响应行为的能力，对分析物响应的水凝胶在广泛的应用中得到了广泛的应用。在本专题介绍中，我们讨论了制造四类不同的对分析物响应的水凝胶的策略，具体为非印迹、分子印迹、含有生物分子和酶响应的水凝胶。然后，我们探讨了这些材料如何被纳入传感器和药物输送系统中，并强调了展示这些材料多功能性的示例。例如，除了对分析物响应的水凝胶的分子识别特性之外，还可以利用分析物结合引起的物理化学变化来产生用于传感应用的可检测信号。随着该领域研究的发展，已经出现了许多用于提高这些传感器的选择性和灵敏度（即检测限）的创造性方法。对于药物输送系统的应用，通过竞争的分子相互作用或网络中的物理化学变化可以触发治疗性释放。此外，在网络中包含可降解单元可以实现持续和响应性的治疗性释放。详细讨论了几个利用水凝胶对分析物响应的行为来治疗癌症、糖尿病和肠易激综合征的令人兴奋的示例。我们预计，在设计对分析物响应的水凝胶时使用的创造性和组合方法将继续为传感和药物输送领域带来具有巨大潜力的材料。
