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.
