Stimulus-Responsive Zwitterionic Prodrug Delivery System with Sustained Release of Hydrogen Sulfide for Protective Aortic Dissection

Aortic dissection (AD) is one of the most frequent types of aortic disease with extremely poor prognosis. The biological signaling gas hydrogen sulfide (H 2 S) has exhibited protective effects in various types of cardiovascular diseases. However, as a toxic, colorless gas, the application of H 2 S is immensely hampered due to the lack of ideal donors. In this article, a drug delivery system with a H 2 S donor has been prepared. Meanwhile, the donor could be deposed in a cysteine-containing environment to generate H 2 S. The results indicate that the H 2 S donor polymer nanomicelles mitigated the processive transformation of smooth muscle cells effectively in a proper concentration range, which may play a protective role in aortic dissection. In animal experiments, the sustained-release H 2 S donor stimulated in the presence of cysteine was found to demonstrate beneficial effects in a murine model of aortic dissection and would likely become a potential target of H 2 S therapy for cardiovascular diseases.