Novel controlled and targeted releasing hydrogen sulfide system exerts combinational cerebral and myocardial protection after cardiac arrest

BACKGROUND: Cardiac arrest (CA) is a leading cause of death worldwide. Even after successful cardiopulmonary resuscitation (CPR), the majorities of survivals are companied with permanent myocardial and cerebral injury. Hydrogen sulfide (H(2)S) has been recognized as a novel gasotransmitter exerting multiple organ protection; however, the lacks of ideal H(2)S donors which can controlled release H(2)S to targeted organs such as heart and brain limits its application. RESULTS: This work utilized mesoporous iron oxide nanoparticle (MION) as the carriers of diallyl trisulfide (DATS), with polyethylene glycol (PEG) and lactoferrin (LF) modified to MIONs to acquire the prolonged circulation time and brain-targeting effects, and a novel targeted H(2)S releasing system was constructed (DATS@MION-PEG-LF), which exhibited excellent biocompatibility, controlled-releasing H(2)S pattern, heart and brain targeting features, and the ability to be non-invasive traced by magnetic resonance imaging. DATS@MION-PEG-LF presented potent protective effects against cerebral and cardiac ischemic injury after CA in both in vitro hypoxia/reoxygenation models and in vivo CA/CPR models, which mainly involves anti-apoptosis, anti-inflammatory and anti-oxidant mechanisms. Accordingly, the cardiac and cerebral functions were obviously improved after CA/CPR, with potentially improved survival. CONCLUSIONS: The present work provides a unique platform for targeted controlled release of H(2)S based on MIONs, and offers a new method for combinational myocardial and cerebral protection from ischemic injury, bringing considerable benefits for CA patients. [Image: see text]