Superoxide anion-responsive persulfide and all-trans retinoic acid co-donating peptide assemblies attenuate myocardial ischemia-reperfusion injury

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials Pub Date : 2025-03-18 DOI:10.1016/j.biomaterials.2025.123276

Yanwen Zhang , Yuxuan Ge , Shiqi Wu , Yiyang Shao , Yujia Lu , Xueshan Zhao , Jun Gu , Yin Wang

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引用次数: 0

Abstract

Myocardial ischemia-reperfusion injury (MIRI) has become a severe threat to human health due to its high mortality rate and poor prognosis. Mutually entangled issues including ROS over-production, excessive inflammatory responses, and myocardial apoptosis are involved during MIRI. Effective inhibition of ROS burst at the beginning of reperfusion has been proved as the key for MIRI treatment. In this work, we report a superoxide anion-responsive peptide co-assembly (S/A-P) capable of delivering the H₂S donor (i.e., superoxide-responsive persulfide donor) and all-trans retinoic acid (ATRA) simultaneously for the treatment. Our results suggest that compared with its single peptidic counterparts, the as-prepared system can significantly lower ROS production and repair myocardial mitochondrial dysfunction due to the synergy effect from the persulfides/H₂S and ATRA. Moreover, S/A-P can reduce excessive inflammatory response through regulating macrophage polarization, which is further mapped by RNA sequencing. In vivo assessment of the co-assembly also displays an excellent therapeutic effect of MIRI on rats. In terms of good biocompatibility and outstanding efficacy, we believe that S/A-P will have a bright future for the treatment of cardiovascular diseases or other related diseases.

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超氧阴离子反应性过氧化物和全反式维甲酸共供肽组合可减轻心肌缺血再灌注损伤

心肌缺血再灌注损伤（MIRI）因其死亡率高、预后差，已成为严重威胁人类健康的疾病。MIRI涉及ROS过度产生、过度炎症反应和心肌凋亡等相互纠缠的问题。有效抑制再灌注开始时ROS爆发已被证明是MIRI治疗的关键。在这项工作中，我们报道了一种超氧阴离子响应肽共组装（S/ a - p）能够同时传递H2S供体（即超氧响应过硫供体）和全反式维甲酸（ATRA）进行治疗。我们的研究结果表明，由于过硫化物/H2S和ATRA的协同作用，与单一肽相比，制备的体系可以显著降低ROS的产生并修复心肌线粒体功能障碍。此外，S/A-P可以通过调节巨噬细胞极化来减少过度的炎症反应，这一点进一步通过RNA测序来定位。体内对共组装的评估也显示了MIRI对大鼠的良好治疗效果。从良好的生物相容性和突出的疗效来看，我们相信S/ a - p在治疗心血管疾病或其他相关疾病方面具有广阔的前景。

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来源期刊

Biomaterials 工程技术-材料科学：生物材料

CiteScore

26.00

自引率

2.90%

发文量

565

审稿时长

46 days

期刊介绍： Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.