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载 MnO/GdO 基元白蛋白纳米复合材料用于兔模型急性心肌梗死的精确磁共振成像

Albumin nanocomposites with MnO/GdO motifs for precise MR imaging of acute myocardial infarction in rabbit models.

机构信息

Department of Radiology, Center for Medical Imaging, And State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 10041, China.

Department of Radiology, Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, 20# South Renmin Road, Chengdu, Sichuan, 610041, China.

出版信息

Biomaterials. 2020 Feb;230:119614. doi: 10.1016/j.biomaterials.2019.119614. Epub 2019 Nov 12.

Abstract

The severe mortality and morbidity of myocardial infarction requests appropriate and accurate detection. Considering pathological profile of the acidic myocardial infarction microenvironments, herein, the low pH-sensitive albumin nanocomposites with MnO motifs (MnO@BSA) have been engineered for T-weighted MR imaging of myocardial infarction, while using non-pH-responsive GdO@BSA nanocomposites as control. The nanocomposites were 20-30 nm in diameter with spheroid morphology. Besides, the MnO@BSA have exhibited pH-triggered releasing of Mn, demonstrating approximately 38-fold and 55-fold increased molecular relaxivity at acute myocardial infarction-mimicking pH 6.5 (13.08 mMs) and macrophage intracellular pH 5.0 (18.76 mMs) compared to the extremely low relaxivity (0.34 mMs) at normal physiological conditions (pH 7.4). However, the GdO@BSA with molecular relaxivity approximately 10 mMs were without pH-sensitive properties. Furthermore, the MnO@BSA have demonstrated high accumulation in the acute myocardial infarction regions and fast metabolism from the body after systemic injection, accounting high contrast enhancement for accurate MR imaging of acute myocardial infarction in rabbit models, demonstrating better diagnostic performance over the controls.

摘要

心肌梗死的高死亡率和高发病率要求进行适当和准确的检测。考虑到酸性心肌梗死微环境的病理特征,本文设计了具有 MnO 图案的低 pH 敏感白蛋白纳米复合材料(MnO@BSA),用于心肌梗死的 T1 加权磁共振成像,同时使用非 pH 响应的 GdO@BSA 纳米复合材料作为对照。纳米复合材料的直径为 20-30nm,呈球形形态。此外,MnO@BSA 表现出 pH 触发的 Mn 释放,与正常生理条件(pH 7.4)下极低的弛豫率(0.34 mMs)相比,在模拟急性心肌梗死的 pH 6.5(13.08 mMs)和巨噬细胞细胞内 pH 5.0(18.76 mMs)下表现出约 38 倍和 55 倍的分子弛豫率增加。然而,具有约 10 mMs 分子弛豫率的 GdO@BSA 没有 pH 敏感性。此外,MnO@BSA 在全身注射后在急性心肌梗死区域有很高的积累,并在体内快速代谢,为兔模型的急性心肌梗死的准确磁共振成像提供了高对比增强,表现出优于对照的诊断性能。

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