Institut des Sciences Moléculaires, ENSCBP, Université Bordeaux, 16 Av. Pey Berland, 33607 Pessac Cedex, France.
Langmuir. 2011 Oct 18;27(20):12693-701. doi: 10.1021/la202910k. Epub 2011 Sep 21.
We report on the synthesis of various glucose-responsive microgels based on N-alkylacrylamide derivatives and phenylboronic acid (PBA) as a glucose sensing moiety. Depending on their chemical composition, the microgels exhibit opposite behaviors in response to glucose concentration increase: they can either swell or shrink, using two different mechanisms for glucose recognition. Both behaviors may be suitable for glucose sensing and insulin delivery. When glucose binds a single boronate receptor, the microgel swells as glucose concentration increases. This mechanism can be used to deliver a drug by diffusion through the network. In other cases, glucose binds specifically to two boronates, which creates additional cross-links within the network and provokes shrinkage. Such systems are promising for the development of sensors with improved selectivity and also as potential "intelligent" valves in microfabricated delivery systems. By a rational choice of the constituting units of the network structure, we show how to favor one or the other type of response to glucose variation. Therefore, glucose-swelling microgels operating under physiological conditions have been obtained by copolymerization with an appropriate choice of alkylacrylamide monomer and boronate derivative. At a pH above the pK(a) of the boronic acid derivative, the same structures shrink in response to glucose concentration. The nature of the cross-linker is a key parameter to enable this dual behavior. In other microgels, an amine group is introduced in the vicinity of the boronic acid, which lowers its pK(a) and favors microgel contraction at physiological pH. This work has allowed us to give some general rules to control the swelling/shrinking behavior of glucose-responsive microgels.
我们报告了基于 N-烷基丙烯酰胺衍生物和苯硼酸（PBA）作为葡萄糖传感部分的各种葡萄糖响应性微凝胶的合成。根据它们的化学组成，微凝胶对葡萄糖浓度增加表现出相反的行为：它们可以通过两种不同的机制膨胀或收缩，用于葡萄糖识别。这两种行为都可能适用于葡萄糖感测和胰岛素输送。当葡萄糖结合单个硼酸受体时，微凝胶随着葡萄糖浓度的增加而膨胀。这种机制可用于通过网络扩散来输送药物。在其他情况下，葡萄糖特异性地结合两个硼酸酯，这会在网络内创建额外的交联并引起收缩。这些系统有望开发出具有改进选择性的传感器，也有望成为微制造输送系统中的潜在“智能”阀。通过对网络结构的组成单元进行合理选择，我们展示了如何有利于对葡萄糖变化的一种或另一种类型的响应。因此，通过与合适的烷基丙烯酰胺单体和硼酸酯衍生物共聚，可以获得在生理条件下起作用的葡萄糖膨胀微凝胶。在硼酸盐衍生物的 pK(a)以上的 pH 值下，相同的结构会响应葡萄糖浓度而收缩。交联剂的性质是实现这种双重行为的关键参数。在其他微凝胶中，在硼酸附近引入了一个胺基，降低了其 pK(a)并有利于在生理 pH 值下微凝胶收缩。这项工作使我们能够给出一些控制葡萄糖响应性微凝胶的膨胀/收缩行为的一般规则。
