Wang Yin, Matson John B
Department of Chemistry, Virginia Tech Center for Drug Discovery, and Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA 24061, United States.
ACS Appl Bio Mater. 2019 Nov 18;2(11):5093-5098. doi: 10.1021/acsabm.9b00768. Epub 2019 Oct 16.
Hydrogen sulfide (HS), an endogenously generated and regulated signaling gas, plays a vital role in a variety of (patho)physiological processes. In the past few years, different kinds of HS-releasing compounds (often referred to as HS donors) have been developed for HS delivery, but it is still challenging to make HS donors with tunable payloads in a simple and efficient manner. Herein, a series of peptide-HS donor conjugates (PHDCs) with tunable donor loadings are designed for controlled HS release. The PHDCs self-assemble into nanoribbons with different geometries in aqueous solution. Upon addition of cysteine, these nanostructures release HS, delivering their payload into H9C2 cells, as visualized using an HS-selective fluorescent probe. Beyond imaging, studies show that the ability of PHDCs to mitigate doxorubicin-induced cardiotoxicity in H9C2 cardiomyocytes depends on their nanostructures and HS release profiles. This strategy may enable the development of sophisticated HS-releasing biomaterials for drug delivery and regenerative medicine.
硫化氢（HS）是一种内源性生成且受调控的信号气体，在多种（病理）生理过程中发挥着至关重要的作用。在过去几年里，已开发出不同种类的硫化氢释放化合物（通常称为HS供体）用于硫化氢递送，但以简单有效的方式制备具有可调节载量的HS供体仍然具有挑战性。在此，设计了一系列具有可调节供体负载量的肽 - HS供体缀合物（PHDCs）用于可控的HS释放。PHDCs在水溶液中自组装成具有不同几何形状的纳米带。加入半胱氨酸后，这些纳米结构释放HS，使用HS选择性荧光探针可视化观察到其将负载物递送至H9C2细胞中。除成像外，研究表明PHDCs减轻阿霉素诱导的H9C2心肌细胞心脏毒性的能力取决于其纳米结构和HS释放曲线。该策略可能有助于开发用于药物递送和再生医学的复杂HS释放生物材料。
