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

Abstract

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 prolong 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.

Keywords:

• steady release
• porous structure
• biocompatibility
• biodegeneration

Supplementary material

Figure S1 The scheme of microstructure of DATS-MIONs and the process of releasing hydrogen sulfide.

Abbreviations: DATS, diallyl trisulfide; GSH, glutathione; H₂S, Hydrogen Sulfide; MIONs, mesoporous iron oxide nanoparticles.

Figure S2 (A) Illustration of dual-modal SRS/TA microscopy. (B) Time-resolved TA dynamics of Fe₃O₄ nanoparticles and femtosecond SRS curves of oleic acid. (C) SRS images of Kupffer cells and TA images of intracellular Fe₃O₄ detected at the two time delays (τ) marked in (B). Scale bar: 5 µm.

Abbreviations: ODL, optical delay line; DM, dichroic mirror; EOM, electro-optical modulator; SP, shortpass filter; PD, photodiode; LIA, lock-in amplifier; SRS, stimulated Raman scattering; TA, transient absorption.

Acknowledgments

This work was supported by Shanghai Sailing Program (grant number 17YF1402100) and Natural Science Foundation of China (grant number 81801844).

Disclosure

The authors report no conflicts of interest in this work.