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一种多功能集成的无金属磁共振成像试剂用于早期诊断糖尿病心肌病小鼠模型中的氧化应激。

A Multifunctional Integrated Metal-Free MRI Agent for Early Diagnosis of Oxidative Stress in a Mouse Model of Diabetic Cardiomyopathy.

机构信息

College of Polymer Science and Engineering, State Key Laboratory of Polymer Material and Engineering, Sichuan University, Chengdu, 610065, P. R. China.

Department of Radiology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital, Sichuan University, 20# South Renmin Road, Chengdu, Sichuan, 610041, P. R. China.

出版信息

Adv Sci (Weinh). 2023 Mar;10(7):e2206171. doi: 10.1002/advs.202206171. Epub 2023 Jan 3.

Abstract

Reactive oxygen species (ROS) are closely associated with the progression of diabetic cardiomyopathy (DCM) and can be regarded as one of its early biomarkers. Magnetic resonance imaging (MRI) is emerging as a powerful tool for the detection of cardiac abnormalities, but the sensitive and direct ROS-response MRI probe remains to be developed. This restricts the early diagnosis of DCM and prevents timely clinical interventions, resulting in serious and irreversible pathophysiological abnormalities. Herein, a novel ROS-response contrast-enhanced MRI nanoprobe (RCMN) is developed by multi-functionalizing fluorinated carbon nanosheets (FCNs) with multi-hydroxyl and 2,2,6,6-tetramethylpiperidin-1-oxyl groups. RCMNs capture ROS and then gather in the heart provisionally, which triggers MRI signal changes to realize the in vivo detection of ROS. In contrast to the clinical MRI agents, the cardiac abnormalities of disease mice is detected 8 weeks in advance with the assistance of RCMNs, which greatly advances the diagnostic window of DCM. To the best of the knowledge, this is the first ROS-response metal-free T -weighted MRI probe for the early diagnosis of DCM mice model. Furthermore, RCMNs can timely scavenge excessively produced ROS to alleviate oxidative stress.

摘要

活性氧(ROS)与糖尿病心肌病(DCM)的进展密切相关,可作为其早期生物标志物之一。磁共振成像(MRI)作为一种检测心脏异常的强大工具正在兴起,但敏感且直接的 ROS 反应 MRI 探针仍有待开发。这限制了 DCM 的早期诊断,并阻止了及时的临床干预,导致严重和不可逆转的病理生理异常。在此,通过多功能化含氟碳纳米片(FCN)上的多羟基和 2,2,6,6-四甲基哌啶-1-氧自由基基团,开发了一种新型的 ROS 反应性对比增强 MRI 纳米探针(RCMN)。RCMN 捕获 ROS,然后暂时聚集在心脏中,触发 MRI 信号变化,从而实现体内 ROS 的检测。与临床 MRI 造影剂相比,借助 RCMN 可以提前 8 周检测到疾病小鼠的心脏异常,大大提前了 DCM 的诊断窗口。据我们所知,这是第一个用于早期诊断 DCM 小鼠模型的 ROS 反应性无金属 T1 加权 MRI 探针。此外,RCMN 还可以及时清除过多产生的 ROS,从而减轻氧化应激。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e27/9982554/1a18a0339845/ADVS-10-2206171-g004.jpg

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