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基于双模态氧化铁纳米粒子的可控释放硫化氢供体保护心肌组织免受缺血再灌注损伤。

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

机构信息

Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai 200030, China,

Department of Radiology, Second People's Hospital of Nantong City, Nantong 226002, Jiangsu, China.

出版信息

Int J Nanomedicine. 2019 Jan 30;14:875-888. doi: 10.2147/IJN.S186225. eCollection 2019.

Abstract

BACKGROUND

Hydrogen sulfide (HS) 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 HS 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 HS 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 HS 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 HS donor for research and medical purposes.

摘要

背景

硫化氢 (HS) 在逆转心血管系统多种病理生理过程方面显示出有希望的治疗益处,包括心肌缺血再灌注 (IR) 损伤。然而,实现 HS 的控制和持续释放一直是限制该气体分子临床应用的技术瓶颈。

方法

本研究描述了载有二烯丙基三硫(DATS)的介孔氧化铁纳米粒子(MIONs)的开发,DATS 是 HS 供体化合物,并通过受激拉曼散射/瞬态吸收进行了校准。

结果

合成的 MIONs 具有优异的介孔性和窄的粒径分布,这使它们能够将 HS 的释放速度减慢到合适的速度,并延长平台期。DATS-MIONs 的控制释放特性在体外和体内均没有不良影响,并且在心肌缺血的小鼠模型中观察到它们对经历 IR 损伤的心脏组织的保护作用。DATS-MIONs 被位于肝脏中的专门巨噬细胞库普弗细胞快速生物降解,这导致有限的肝脏代谢负担。

结论

持续释放模式和优异的生物相容性使 DATS-MIONs 成为研究和医学用途有前途的 HS 供体。

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