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用于肝缺血再灌注损伤中连续成像氧化还原平衡的动态可逆 MRI 纳米探针。

Dynamic-Reversible MRI Nanoprobe for Continuous Imaging Redox Homeostasis in Hepatic Ischemia-Reperfusion Injury.

机构信息

State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China.

College of Electrical and Information Engineering, Hunan University, Changsha 410082, China.

出版信息

ACS Nano. 2023 May 23;17(10):9529-9542. doi: 10.1021/acsnano.3c02265. Epub 2023 May 8.

Abstract

Hepatic ischemia-reperfusion (I/R) injury accompanied by oxidative stress is responsible for postoperative liver dysfunction and failure of liver surgery. However, the dynamic non-invasive mapping of redox homeostasis in deep-seated liver during hepatic I/R injury remains a great challenge. Herein, inspired by the intrinsic reversibility of disulfide bond in proteins, a kind of reversible redox-responsive magnetic nanoparticles (RRMNs) is designed for reversible imaging of both oxidant and antioxidant levels (ONOO/GSH), based on sulfhydryl coupling/cleaving reaction. We develop a facile strategy to prepare such reversible MRI nanoprobe one-step surface modification. Owing to the significant change in size during the reversible response, the imaging sensitivity of RRMNs is greatly improved, which enables RRMNs to monitor the tiny change of oxidative stress in liver injury. Notably, such reversible MRI nanoprobe can non-invasively visualize the deep-seated liver tissue slice by slice in living mice. Moreover, this MRI nanoprobe can not only report molecular information about the degree of liver injury but also provide anatomical information about where the pathology occurred. The reversible MRI probe is promising for accurately and facilely monitoring I/R process, accessing injury degree and developing powerful strategy for precise treatment.

摘要

肝脏缺血再灌注(I/R)损伤伴随着氧化应激,是导致肝手术后肝功能障碍和衰竭的原因。然而,在肝 I/R 损伤期间,对深部肝脏中氧化还原平衡的动态无创映射仍然是一个巨大的挑战。在此,受蛋白质中二硫键内在可逆性的启发,我们设计了一种基于巯基偶联/断裂反应的可逆氧化还原响应性磁性纳米粒子(RRMNs),用于氧化剂和抗氧化剂水平(ONOO/GSH)的可逆成像。我们开发了一种简便的策略来制备这种可逆 MRI 探针——一步表面修饰。由于在可逆响应过程中尺寸发生显著变化,RRMNs 的成像灵敏度大大提高,这使得 RRMNs 能够监测肝损伤中氧化应激的微小变化。值得注意的是,这种可逆 MRI 探针可以在活体小鼠中无创地对深部肝组织进行逐层可视化。此外,这种 MRI 探针不仅可以报告关于肝损伤程度的分子信息,还可以提供关于病理学发生位置的解剖学信息。这种可逆 MRI 探针有望准确、简便地监测 I/R 过程,评估损伤程度,并为精准治疗提供强大策略。

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