Dai Jianfeng, Wei Weijun, Yan Chenxu, Ji Ding-Kun, Liu Caiqi, Huang Jialiang, Liang Chenyi, Liu Jianjun, Guo Zhiqian, Zhu Wei-Hong
Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Institute of Fine Chemicals, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai, China.
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
Nat Biomed Eng. 2025 May 13. doi: 10.1038/s41551-025-01392-x.
The dynamic behaviour of amyloid-β (Aβ) plaques in Alzheimer's disease remains poorly understood, and accumulation and distribution of Aβ plaques must be inferred from in vitro pathological changes in brain tissue. In situ detection of Aβ plaques in live imaging is challenging because of the lack of adequate probes. Here we report the design of unimolecular quinoline-malononitrile-based Aβ probes, termed QMFluor integrative framework, that binds in vivo to Aβ plaques, making them detectable via near-infrared fluorescence imaging, magnetic resonance imaging, positron emission tomography and computed tomography. QMFluor probes are permeable to the blood-brain barrier, and, upon systematic injection, enable real-time magnetic resonance imaging and positron emission tomography-computed tomography imaging of the Aβ biodistribution in the hippocampus and cerebral cortex, and accurately differentiate the brains of living Alzheimer's disease mouse models from wild-type controls. We further demonstrate the ability of QMFluor probes to reach the brain after intravenous injection in a large animal model. This strategy expands the toolbox of probes for in vivo visualization of amyloids in Alzheimer's disease pathological analysis, drug screening and clinical applications.
阿尔茨海默病中β淀粉样蛋白（Aβ）斑块的动态行为仍知之甚少，Aβ斑块的积累和分布必须从脑组织的体外病理变化中推断出来。由于缺乏合适的探针，在活体成像中原位检测Aβ斑块具有挑战性。在此，我们报告了基于单分子喹啉-丙二腈的Aβ探针的设计，称为QMFluor整合框架，其在体内与Aβ斑块结合，使其能够通过近红外荧光成像、磁共振成像、正电子发射断层扫描和计算机断层扫描进行检测。QMFluor探针可透过血脑屏障，经静脉注射后，能够对海马体和大脑皮层中Aβ的生物分布进行实时磁共振成像以及正电子发射断层扫描-计算机断层扫描成像，并准确区分活体阿尔茨海默病小鼠模型的大脑与野生型对照。我们进一步证明了QMFluor探针在大型动物模型中静脉注射后能够到达大脑。该策略扩展了用于阿尔茨海默病病理分析、药物筛选和临床应用中淀粉样蛋白体内可视化的探针工具箱。
