Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware 19716, United States.
Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, United States.
J Am Chem Soc. 2020 Mar 11;142(10):4671-4679. doi: 10.1021/jacs.9b11564. Epub 2020 Feb 26.
Photolabile moieties have been utilized in applications ranging from peptide synthesis and controlled protein activation to tunable and dynamic materials. The photochromic properties of nitrobenzyl (NB) based linkers are readily tuned to respond to cytocompatible light doses and are widely utilized in cell culture and other biological applications. While widely utilized, little is known about how the microenvironment, particularly confined aqueous environments (e.g., hydrogels), affects both the mode and rate of cleavage of NB moieties, leading to unpredictable limitations in control over system properties (e.g., rapid hydrolysis or slow photolysis). To address these challenges, we synthesized and characterized the photolysis and hydrolysis of NB moieties containing different labile bonds (i.e., ester, amide, carbonate, or carbamate) that served as labile crosslinks within step-growth hydrogels. We observed that NB ester bond exhibited significant rates of both photolysis and hydrolysis, whereas, importantly, the NB carbamate bond had superior light responsiveness and resistance to hydrolysis within the hydrogel microenvironment. Exploiting this synergy and orthogonality of photolytic and hydrolytic degradation, we designed concentric cylinder hydrogels loaded with different cargoes (e.g., model protein with different fluorophores) for either combinatorial or sequential release, respectively. Overall, this work provides new facile chemical approaches for tuning the degradability of NB linkers and an innovative strategy for the construction of multimodal degradable hydrogels, which can be utilized to guide the design of not only tunable materials platforms but also controlled synthetic protocols or surface modification strategies.
光不稳定部分已被广泛应用于从肽合成和控制蛋白质激活到可调谐和动态材料的各种领域。基于硝基苄基 (NB) 的连接物的光致变色性质可以很容易地被调节以响应细胞相容性的光剂量，并广泛应用于细胞培养和其他生物学应用中。虽然被广泛应用，但对于微环境（特别是受限的水相环境，如水凝胶）如何影响 NB 部分的断裂模式和速率知之甚少，这导致对系统性质的控制存在不可预测的限制（例如，快速水解或缓慢光解）。为了解决这些挑战，我们合成并表征了含有不同不稳定键（即酯、酰胺、碳酸酯或氨基甲酸酯）的 NB 部分的光解和水解，这些键作为逐步增长水凝胶中的不稳定交联。我们观察到 NB 酯键表现出显著的光解和水解速率，而重要的是，NB 氨基甲酸酯键在水凝胶微环境中具有更好的光响应性和抗水解性。利用这种光解和水解降解的协同作用和正交性，我们设计了同心圆筒水凝胶，分别装载不同的货物（例如具有不同荧光团的模型蛋白），用于组合或顺序释放。总的来说，这项工作为调节 NB 连接物的可降解性提供了新的简便化学方法，并为构建多模式可降解水凝胶提供了创新策略，可用于指导不仅可调材料平台的设计，还可指导控制合成方案或表面改性策略的设计。
