Controlled-releasing hydrogen sulfide donor based on dual-modal iron oxide nanoparticles protects myocardial tissue from ischemia-reperfusion injury

Background: Hydrogen sulfide (H2S) has shown promising therapeutic benefits in reversing a variety of pathophysiological processes in cardiovascular system, including myocardial ischemia-reperfusion (IR) injury. However, the achievement of controlled and sustained release of H2S has been a technical bottleneck that limits the clinical application of the gas molecule. Methods: The current study describes the development of mesoporous iron oxide nanoparticles (MIONs) which were loaded with diallyl trisulfide (DATS), a H2S donor compound, and calibrated by stimulated Raman scattering/transient absorption. Results: The synthesized MIONs were characterized with excellent mesoporosity and a narrow size distribution, which enabled them to slow down the release of H2S to a suitable rate and pro-long the plateau period. The controlled-release feature of DATS-MIONs resulted in little adverse effect both in vitro and in vivo, and their protective effect on the heart tissue that underwent IR injury was observed in the mouse model of myocardial ischemia. The rapid biodegradation of DATS-MIONs was induced by Kupffer cells, which were specialized macrophages located in the liver and caused limited hepatic metabolic burden. Conclusion: The sustained-release pattern and excellent biocompatibility make DATS-MIONs a promising H2S donor for research and medical purposes.