Dao Pascal, Ye Feifei, Liu Yan, Du Zhi Yun, Zhang Kun, Dong Chang Zhi, Meunier Bernard, Chen Huixiong
Faculty of Light Industry and Chemical Engineering, Guang Dong University of Technology , Guangzhou, Guang Dong 510006, China.
Université Paris Diderot, Sorbonne Paris Cité , ITODYS, UMR 7086 CNRS, 15 rue J-A de Baïf, 75205 Cedex 13 Paris, France.
ACS Chem Neurosci. 2017 Apr 19;8(4):798-806. doi: 10.1021/acschemneuro.6b00380. Epub 2017 Feb 2.
Early detection of Alzheimer's disease (AD) is imperative in enabling the understanding and clinical treatment of this disorder, as well as in preventing its progression. Imaging agents specifically targeting Aβ plaques in the brain and the retina may lead to the early diagnosis of AD. Among them, near-infrared fluorescent (NIRF) imaging has emerged as an attractive tool to noninvasively identify and monitor diseases during the preclinical and early stages. In the present study, we report the design, synthesis, and evaluation of a series of new near-infrared fluorescent probes. Most of these probes displayed maximum emission in PBS (>650 nm), which falls in the good range for NIRF probes. Among them, 4a1 showed the highest affinity toward Aβ aggregates (K = 7.5 nM) and an excellent targeting ability for Aβ plaques in slices of brain and retina tissue from double transgenic mice. These compounds are also found to effectively prevent Aβ fibril formation and disaggregate preformed Aβ fibrils, showing a promising potential as theranostic agents for the diagnosis and therapy of AD.
阿尔茨海默病（AD）的早期检测对于理解和临床治疗这种疾病以及预防其进展至关重要。专门针对大脑和视网膜中Aβ斑块的成像剂可能有助于AD的早期诊断。其中，近红外荧光（NIRF）成像已成为一种有吸引力的工具，可在临床前和早期阶段非侵入性地识别和监测疾病。在本研究中，我们报告了一系列新型近红外荧光探针的设计、合成和评估。这些探针中的大多数在PBS中显示出最大发射波长（>650 nm），这对于NIRF探针来说处于良好范围。其中，4a1对Aβ聚集体表现出最高亲和力（K = 7.5 nM），并且对双转基因小鼠脑和视网膜组织切片中的Aβ斑块具有出色的靶向能力。这些化合物还被发现能有效防止Aβ纤维形成并使预先形成的Aβ纤维解聚，显示出作为AD诊断和治疗的诊疗试剂的潜在前景。
