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Novel controlled and targeted releasing hydrogen sulfide system exerts combinational cerebral and myocardial
Xiaotian Sun1, Yiqing Wang2, Shuyan Wen2
1Department of Cardiothoracic Surgery, Huashan Hospital of Fudan University, 12th Wulumuqi Rd, 200040, Shanghai, China. sunxiaotian@126.com.
Insights
A novel hydrogen sulfide (H2S) delivery system using mesoporous iron oxide nanoparticles (MIONs) targets the heart and brain, offering protection against cardiac arrest injury and improving survival rates.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cardiovascular Research
Background:
- Cardiac arrest (CA) is a major global cause of death.
- Survivors often suffer permanent myocardial and cerebral damage despite successful CPR.
- Hydrogen sulfide (H2S) shows organ-protective potential but lacks targeted delivery methods.
Purpose of the Study:
- To develop a targeted H2S delivery system for myocardial and cerebral protection after CA.
- To create a system with controlled H2S release and non-invasive monitoring capabilities.
Main Methods:
- Mesoporous iron oxide nanoparticles (MIONs) were used as carriers for diallyl trisulfide (DATS).
- MIONs were modified with polyethylene glycol (PEG) and lactoferrin (LF) for prolonged circulation and brain targeting.
- The DATS@MION-PEG-LF system was evaluated in vitro and in vivo CA/CPR models.
Main Results:
- The DATS@MION-PEG-LF system demonstrated biocompatibility, controlled H2S release, and heart/brain targeting.
- It showed potent protection against cerebral and cardiac ischemic injury via anti-apoptosis, anti-inflammatory, and anti-oxidant mechanisms.
- Significant improvements in cardiac and cerebral function were observed post-CA/CPR, with potential for improved survival.
Conclusions:
- A novel MION-based platform enables targeted, controlled H2S release.
- This offers a new strategy for combined myocardial and cerebral protection against ischemic injury.
- The system holds promise for improving outcomes in cardiac arrest patients.
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 (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.
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 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.
Conclusions:
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.
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