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使用混合纳米GdF造影剂对β淀粉样蛋白进行双光子荧光和磁共振特异性成像

Two-Photon Fluorescence and Magnetic Resonance Specific Imaging of Aβ Amyloid Using Hybrid Nano-GdF Contrast Media.

作者信息

Mpambani Francis, Åslund Andreas K O, Lerouge Frederic, Nyström Sofie, Reitan Nina, Huuse Else Marie, Widerøe Marius, Chaput Frederic, Monnereau Cyrille, Andraud Chantal, Lecouvey Marc, Handrick Susann, Prokop Stefan, Heppner Frank L, Nilsson Peter, Hammarström Per, Lindgren Mikael, Parola Stephane

机构信息

Laboratoire de Chimie ENS Lyon, Université de Lyon, Ecole Normale Supérieure de Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5182, 46 allée d'Italie, 69364 Lyon, France.

Department of Physics, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway.

出版信息

ACS Appl Bio Mater. 2018 Aug 20;1(2):462-472. doi: 10.1021/acsabm.8b00191. Epub 2018 Jul 30.

Abstract

Real time detection of Amyloid β (Aβ) deposits at an early stage may lead to faster and more conclusive diagnosis of Alzheimer's disease (AD) and can facilitate the follow up of the effect of therapeutic interventions. In this work, the capability of new hybrid nanomaterials to target and detect Aβ aggregates using magnetic resonance (MRI) and fluorescence imaging is demonstrated. These smart contrast agents contain paramagnetic nanoparticles surrounded by luminescent conjugated oligothiophenes (LCOs) known to selectively bind to Aβ aggregates, with emission spectra strongly dependent on their conformations, opening the possibilities for several fluorescence imaging modes for AD diagnostics. Relaxivity is evaluated and . The capability of these contrast media to link to Aβ fibrils in stained sections is revealed using transmission electron microscopy and fluorescence microscopy. Preliminary experiments show the ability of the contrast agent to diffuse through the blood-brain barrier of model animals and specifically stain amyloid deposits.

摘要

早期实时检测β淀粉样蛋白(Aβ)沉积物可能会加快阿尔茨海默病(AD)的诊断并得出更具结论性的诊断结果,还能便于对治疗干预效果进行跟踪。在这项工作中,展示了新型混合纳米材料利用磁共振成像(MRI)和荧光成像靶向并检测Aβ聚集体的能力。这些智能造影剂包含被发光共轭寡聚噻吩(LCO)包围的顺磁性纳米颗粒,已知LCO可选择性结合Aβ聚集体,其发射光谱强烈依赖于它们的构象,这为AD诊断的多种荧光成像模式开辟了可能性。评估了弛豫率。使用透射电子显微镜和荧光显微镜揭示了这些造影剂与染色切片中Aβ纤维结合的能力。初步实验表明造影剂能够扩散穿过模型动物的血脑屏障并特异性地对淀粉样沉积物进行染色。

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