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用于血脑屏障通透性及时成像及预测急性缺血性脑卒中出血性转化的生物相容 BSA-MnO 纳米颗粒

Biocompatible BSA-MnO nanoparticles for timely permeability imaging of blood-brain barrier and prediction of hemorrhage transformation in acute ischemic stroke.

机构信息

Department of Radiology, Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China.

School of Medical Imaging, Tianjin Medical University, Tianjin 300203, China.

出版信息

Nanoscale. 2021 May 13;13(18):8531-8542. doi: 10.1039/d1nr02015c.

Abstract

Hemorrhage transformation (HT) is a frequent but maybe fatal complication following acute ischemic stroke due to severe damage of the blood-brain barrier (BBB). Quantitative BBB permeability imaging is a promising method to predict HT in stroke patients for a favorable prognosis. However, clinical gadolinium chelate-based magnetic resonance (MR) imaging of the stroke suffers from a relatively low sensitivity and potential side effects of nephrogenic systemic fibrosis and intracranial gadolinium deposition. Herein, BSA-MnO2 nanoparticles (BM NPs) fabricated by a facile disinfection-mimic method were employed for the permeability imaging of BBB in the stroke for the first time. The BM NPs showed a high T1 relaxivity (r1 = 5.9 mM-1 s-1), remarkable MR imaging ability, and good biocompatibility, allowing the noninvasive timely visualization of BBB permeability in the model rats of middle cerebral artery occlusion (MCAO). Furthermore, increased peak intensity, extended imaging duration, and expanded imaging region indicated by BM NPs in MR imaging showed a good prediction for the onset of HT in MCAO rats. Therefore, BM NPs hold an attractive potential to be an alternative biocompatible MR contrast agent for the noninvasive BBB permeability imaging in vivo, benefiting the fundamental research of diverse neurological disorders and the clinical treatment for stroke patients.

摘要

出血转化(HT)是急性缺血性脑卒中后一种常见但可能致命的并发症,其发生机制与血脑屏障(BBB)的严重损伤有关。定量 BBB 通透性成像技术是一种有前途的方法,可以预测脑卒中患者的 HT,从而改善预后。然而,临床基于钆螯合物的磁共振(MR)成像在脑卒中患者中存在相对较低的灵敏度和潜在的副作用,如肾源性系统纤维化和颅内钆沉积。在此,首次采用简便的消毒模拟法制备了 BSA-MnO2 纳米粒子(BM NPs),用于脑卒中 BBB 的通透性成像。BM NPs 具有高 T1 弛豫率(r1 = 5.9 mM-1 s-1)、显著的磁共振成像能力和良好的生物相容性,可实现对大脑中动脉闭塞(MCAO)模型大鼠 BBB 通透性的无创实时可视化。此外,BM NPs 在 MR 成像中表现出的峰值强度增加、成像持续时间延长和成像区域扩大,表明其对 MCAO 大鼠 HT 的发生具有良好的预测作用。因此,BM NPs 作为一种替代的生物相容性磁共振对比剂,具有很大的潜力用于体内 BBB 通透性的无创成像,有利于多种神经疾病的基础研究和脑卒中患者的临床治疗。

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