Department of Chemical and Biological Engineering , University of Wisconsin-Madison , 1415 Engineering Drive , Madison , Wisconsin 53706 , United States.
Department of Chemistry , University of Wisconsin-Madison , 1101 University Avenue , Madison , Wisconsin 53706 , United States.
Biomacromolecules. 2019 Sep 9;20(9):3464-3474. doi: 10.1021/acs.biomac.9b00756. Epub 2019 Aug 8.
We report the design of reactive and hydrolytically degradable multilayers by the covalent layer-by-layer assembly of an azlactone-containing polymer, poly(2-vinyl-4,4-dimethylazlactone), with an acid-degradable, acetal-containing, small-molecule diamine linker. This approach yields cross-linked multilayers that contain (i) residual azlactone reactivity that can be used for further functionalization after fabrication and (ii) acid-labile cross-links that can undergo pH-triggered degradation. Thin films and hollow capsules fabricated using this approach were relatively stable in slightly basic media (pH = 7.4) but eroded and degraded gradually in mildly acidic environments (pH = 5). The residual azlactones in these materials could be functionalized by reaction with hydrophilic or hydrophobic amines to tune physicochemical properties, including surface wetting and rates of degradation/erosion. Interestingly, our results reveal that rates of degradation could be tuned over a broad range (from ∼4 h to ∼10 days) simply by post-fabrication modification of the parent reactive material. We further demonstrate the potential of acetal-containing microcapsules to be used for the acid-triggered release of encapsulated cargo. The results of in vitro experiments reveal that microcapsules loaded with fluorescently labeled dextran can be internalized by mammalian cells and that cell uptake and intracellular degradation were also influenced by the types of functional groups installed post-fabrication. The introduction of acid degradability expands the range of stimuli that can be used to trigger the destruction of these reactive materials to include changes in pH relevant to chemical and biological processes. Our results also introduce an approach to tuning degradation profiles that differs from past strategies used to design degradable multilayers. We conclude that this approach provides a new, useful, and modular platform for the design of stimuli-responsive nano/biointerfaces with transient environmental stability.
我们报告了通过共价层层组装含有氮丙啶的聚合物聚（2-乙烯基-4,4-二甲基氮丙啶）和酸可降解的、含有缩醛的小分子二胺连接体来设计反应性和水解可降解的多层膜。这种方法得到的交联多层膜含有：（i）在制造后可用于进一步功能化的残留氮丙啶反应性；（ii）酸不稳定的交联键，可在 pH 触发下发生降解。使用这种方法制备的薄膜和中空胶囊在略碱性介质（pH = 7.4）中相对稳定，但在轻度酸性环境（pH = 5）中逐渐侵蚀和降解。这些材料中的残留氮丙啶可以通过与亲水性或疏水性胺反应进行功能化，以调节物理化学性质，包括表面润湿性和降解/侵蚀速率。有趣的是，我们的结果表明，通过对母体反应性材料进行后制造修饰，可以在很宽的范围内（从约 4 小时到约 10 天）调节降解速率。我们进一步证明了含有缩醛的微胶囊在酸触发的封装货物释放方面的潜力。体外实验结果表明，负载荧光标记葡聚糖的微胶囊可以被哺乳动物细胞内化，并且细胞摄取和细胞内降解也受到后制造修饰中安装的官能团类型的影响。引入酸降解性将可用于触发这些反应性材料破坏的刺激物的范围扩展到与化学和生物过程相关的 pH 变化。我们的结果还引入了一种与过去用于设计可降解多层膜的策略不同的调节降解曲线的方法。我们得出的结论是，这种方法为设计具有瞬态环境稳定性的响应性纳米/生物界面提供了一种新的、有用的和模块化的平台。
