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 (H2S) has been recognized as a novel gasotransmitter exerting multiple organ protection; however, the lacks of ideal H2S donors which can controlled release H2S to targeted organs such as heart and brain limits its application. This work utilized mesoporous iron oxide

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... ticle (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 H2S releasing system was constructed (DATS@MION-PEG-LF), which exhibited excellent biocompatibility, controlled-releasing H2S 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. The present work provides a unique platform for targeted controlled release of H2S based on MIONs, and offers a new method for combinational myocardial and cerebral protection from ischemic injury, bringing considerable benefits for CA patients.