Delayed Magnetic Resonance Imaging of Alzheimer's Disease by Using Poly(2-(methacryloyloxy)ethyl phosphorylcholine)-Functionalized Nanoprobes.

IF 8.3 2区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY
ACS Applied Materials & Interfaces Pub Date : 2024-12-18 Epub Date: 2024-12-05 DOI:10.1021/acsami.4c17432
Wenyue Li, Xinyi Zhang, Chuang Liu, Yuqiang Ma, Yanjiao Jiang, Ni Zhang, Yi Hou
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Abstract

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, commonly affecting the aged, with pathophysiological changes presenting 15 to 20 years before clinical symptoms. Early diagnosis and intervention are crucial in effectively slowing the progression of AD. In the current study, poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC)-functionalized NaGdF4 nanoparticles (NaGdF4-PMPC) were developed as magnetic resonance imaging (MRI) contrast agents for targeting alpha 7 nicotinic acetylcholine receptors (α7 nAChRs) in AD mice. NaGdF4-PMPC showed excellent biocompatibility, targeting ability, and MRI performance, with the longitudinal molar relaxivity (r1) and transverse molar relaxivity (r2) being 1.21-fold and 1.33-fold higher than those of the clinical contrast agent Gd-DTPA, respectively, resulting in higher-sensitive MR angiography. After intravenous injection, 3D dynamic contrast-enhanced (DCE) MR images with high-resolution vasculature of the mouse brain were obtained. In addition, by using NaGdF4-PMPC, susceptibility-weighted imaging (SWI) signals in AD mouse brains were greatly retained compared to those in healthy mice for 24 h, emphasizing the excellent targeting ability of NaGdF4-PMPC. Furthermore, the CD31, α7 nAChRs, and Thioflavin S staining were also utilized to investigate the relationship among vascular inflammation, α7 nAChRs, and amyloid-β (Aβ) deposition in AD mice. This work highlights a promising targeted imaging strategy for the timely diagnosis of AD.

Abstract Image

聚(2-(甲基丙烯氧基)乙基磷酸胆碱)功能化纳米探针在阿尔茨海默病延迟磁共振成像中的应用
阿尔茨海默病(AD)是最常见的神经退行性疾病之一,常见于老年人,病理生理变化比临床症状早出现15 ~ 20年。早期诊断和干预对于有效减缓阿尔茨海默病的进展至关重要。在本研究中,聚(2-(甲基丙烯氧基)乙基磷酸胆碱)(PMPC)功能化的NaGdF4纳米颗粒(NaGdF4-PMPC)被开发为针对AD小鼠α7烟碱乙酰胆碱受体(α7 nAChRs)的磁共振成像(MRI)造影剂。NaGdF4-PMPC表现出优异的生物相容性、靶向性和MRI性能,其纵向磨牙弛度(r1)和横向磨牙弛度(r2)分别比临床造影剂Gd-DTPA高1.21倍和1.33倍,磁共振血管成像灵敏度更高。静脉注射后,获得具有高分辨率小鼠脑血管的3D动态对比增强(DCE) MR图像。此外,通过使用NaGdF4-PMPC,与健康小鼠相比,在24小时内,AD小鼠大脑中的敏感性加权成像(SWI)信号被大大保留,强调了NaGdF4-PMPC出色的靶向能力。同时利用CD31、α7 nAChRs、Thioflavin S染色研究AD小鼠血管炎症、α7 nAChRs与淀粉样蛋白-β (Aβ)沉积的关系。这项工作强调了一种有希望的靶向成像策略,可以及时诊断阿尔茨海默病。
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来源期刊
ACS Applied Materials & Interfaces
ACS Applied Materials & Interfaces 工程技术-材料科学:综合
CiteScore
16.00
自引率
6.30%
发文量
4978
审稿时长
1.8 months
期刊介绍: ACS Applied Materials & Interfaces is a leading interdisciplinary journal that brings together chemists, engineers, physicists, and biologists to explore the development and utilization of newly-discovered materials and interfacial processes for specific applications. Our journal has experienced remarkable growth since its establishment in 2009, both in terms of the number of articles published and the impact of the research showcased. We are proud to foster a truly global community, with the majority of published articles originating from outside the United States, reflecting the rapid growth of applied research worldwide.
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