Supramolecular nanostructures with tunable donor loading for controlled H₂S release

Hydrogen sulfide (H₂S), 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 H₂S-releasing compounds (often referred to as H₂S donors) have been developed for H₂S delivery, but it is still challenging to make H₂S donors with tunable payloads in a simple and efficient manner. Herein, a series of peptide-H₂S donor conjugates (PHDCs) with tunable donor loadings are designed for controlled H₂S release. The PHDCs self-assemble into nanoribbons with different geometries in aqueous solution. Upon addition of cysteine, these nanostructures release H₂S, delivering their payload into H9C2 cells, as visualized using an H₂S-selective fluorescent probe. Beyond imaging, in vitro studies show that the ability of PHDCs to mitigate doxorubicin-induced cardiotoxicity in H9C2 cardiomyocytes depends on their nanostructures and H₂S release profiles. This strategy may enable the development of sophisticated H₂S-releasing biomaterials for drug delivery and regenerative medicine.