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用于体内成像淀粉样β 物种的双模式近红外荧光染料偶联磁性纳米粒子。

Dual-Modal NIR-Fluorophore Conjugated Magnetic Nanoparticle for Imaging Amyloid-β Species In Vivo.

机构信息

Department Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry, Application of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan, 411105, China.

Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, SAR China.

出版信息

Small. 2018 Jul;14(28):e1800901. doi: 10.1002/smll.201800901. Epub 2018 Jun 7.

DOI:10.1002/smll.201800901
PMID:29882247
Abstract

Senile plaques, the extracellular deposit of amyloid-β (Aβ) peptides, are one of the neuropathological hallmarks found in Alzheimer's disease (AD) brain. The current method of brain imaging of amyloid plaques based on positron emission tomography (PET) is expensive and invasive with low spatial resolution. Thus, the development of sensitive and nonradiative amyloid-β (Aβ)-specific contrast agents is highly important and beneficial to achieve early AD detection, monitor the disease progression, and evaluate the effectiveness of potential AD drugs. Here a neuroprotective dual-modal nanoprobe developed by integrating highly Aβ-specific and turn-on fluorescence cyanine sensors with superparamagnetic iron oxide nanoparticles as an effective near-infrared imaging (NIRI)/magnetic resonance imaging (MRI) contrast agent for imaging of Aβ species in vivo is reported. This Aβ-specific probe is found not only nontoxic and noninvasive, but also highly blood brain barrier permeable. It also shows a potent neuroprotective effect against Aβ-induced toxicities. This nanoprobe is successfully applied for in vivo fluorescence imaging with high sensitivity and selectivity to Aβ species, and MRI with high spatial resolution in an APP/PS1 transgenic mice model. Its potential as a powerful in vivo dual-modal imaging tool for early detection and diagnosis of AD in humans is affirmed.

摘要

老年斑是淀粉样蛋白-β (Aβ) 肽在大脑中的细胞外沉积,是阿尔茨海默病 (AD) 大脑中发现的神经病理学特征之一。目前基于正电子发射断层扫描 (PET) 的脑淀粉样蛋白斑块成像方法昂贵且具有侵入性,空间分辨率低。因此,开发灵敏且无辐射的 Aβ 特异性对比剂对于实现 AD 的早期检测、监测疾病进展以及评估潜在 AD 药物的效果非常重要和有益。本文报道了一种神经保护双模式纳米探针,它将高度 Aβ 特异性和开启荧光菁染料传感器与超顺磁性氧化铁纳米颗粒集成在一起,作为一种有效的近红外成像 (NIRI)/磁共振成像 (MRI) 对比剂,用于体内 Aβ 物种的成像。这种 Aβ 特异性探针不仅无毒、无侵入性,而且还具有很高的血脑屏障通透性。它还表现出针对 Aβ 诱导的毒性的强大神经保护作用。该纳米探针成功地应用于 APP/PS1 转基因小鼠模型中的体内荧光成像,具有高灵敏度和对 Aβ 物种的高选择性,以及具有高空间分辨率的 MRI。它有望成为一种强大的体内双模式成像工具,用于人类 AD 的早期检测和诊断。

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