Department of Chemistry, Virginia Tech Center for Drug Discovery, and Macromolecules Innovation Institute, Virginia Tech, Blacksburg, Virginia 24061, United States.
Biomacromolecules. 2020 Mar 9;21(3):1171-1178. doi: 10.1021/acs.biomac.9b01600. Epub 2020 Feb 13.
Controlled release is an essential requirement for delivery of hydrogen sulfide (HS) because of its reactive nature, short half-life in biological fluids, and toxicity at high concentrations. In this context, HS delivery via hydrogels may be beneficial as they can deliver HS locally at the site of interest. Herein, we employed hydrogels based on aromatic peptide amphiphiles (APAs) with tunable mechanical properties to modulate the rates of HS release. The APAs contained an aromatic -aroylthiooxime (SATO) HS donor attached with a linker to a short IAVEEE hexapeptide. Linker units included carbonyl, substituted -methylenes, alkenyl, and alkyl segments with the goal of evaluating the role of linker structure on self-assembly, capacity for hydrogelation, and HS release rate. We studied each peptide by transmission electron microscopy, circular dichroism spectroscopy, and rheology, and we measured HS release rates from each gel, triggering SATO decomposition and release of HS by addition of cysteine (Cys). Using an HS-selective electrode probe as well as a turn-on fluorescent HS probe in the presence of H9C2 cardiomyocytes, we found that the rate of HS release from the hydrogels depended on the rate of Cys penetration into the nanofiber core with stiffer gels showing longer overall release.
控制释放对于输送硫化氢（HS）至关重要，因为其具有反应性、在生物流体中半衰期短以及在高浓度下具有毒性。在这种情况下，通过水凝胶输送 HS 可能是有益的，因为它们可以在感兴趣的部位局部输送 HS。在此，我们采用了基于具有可调节机械性能的芳香族肽两亲物（APA）的水凝胶来调节 HS 释放速率。APAs 包含与短的 IAVEEE 六肽连接的带有连接体的芳香族 - 芳酰基硫肟（SATO）HS 供体。连接体单元包括羰基、取代的亚甲基、烯基和烷基片段，目的是评估连接体结构对自组装、水凝胶形成能力和 HS 释放速率的作用。我们通过透射电子显微镜、圆二色光谱和流变学研究了每种肽，并且通过添加半胱氨酸（Cys）触发 SATO 分解和 HS 释放来测量每种凝胶的 HS 释放速率。使用 HS 选择性电极探针以及在 H9C2 心肌细胞存在下的 HS 荧光探针，我们发现 HS 从水凝胶中的释放速率取决于 Cys 渗透到纳米纤维核心的速率，刚性凝胶的整体释放时间更长。
