基于双芳环的分子转子型荧光探针的合理设计用于阿尔茨海默病中淀粉样β斑块的高效体内检测。
Rational design of molecular rotor-based fluorescent probes with bi-aromatic rings for efficient in vivo detection of amyloid-β plaques in Alzheimer's disease.
机构信息
Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, China.
Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, China.
出版信息
Eur J Med Chem. 2022 Dec 5;243:114715. doi: 10.1016/j.ejmech.2022.114715. Epub 2022 Aug 30.
The presence of Aβ plaques in the brain is a hallmark of Alzheimer's disease. Here, we designed and synthesized a series of molecular rotors with various bi-aromatic rings and investigated their applications as near-infrared (NIR) probes for Aβ plaques. We found that the interaction with Aβ aggregates hindered the rotational freedom of the molecular rotors, which brought about a noticeable enhancement in fluorescence intensity. Among them, probe 4b (K = 8.5 nM) with a phenyl-pyridine ring showed a 98-fold increase in fluorescence intensity upon binding with Aβ aggregates. In addition, 4b could identify Aβ plaques in brain sections of both a transgenic (Tg) mouse and AD patients. Furthermore, 4b could readily penetrate the mouse blood-brain barrier (brain = 10.11% ID/g) and washed out rapidly. Finally, the NIR imaging with Tg mice confirmed the practical application of 4b in detecting Aβ plaques in vivo. Altogether, our work widens the landscape of Aβ NIR probes and offers a new tool for Aβ detection.
脑内 Aβ 斑块的存在是阿尔茨海默病的一个标志。在这里，我们设计并合成了一系列具有不同双芳环的分子转子，并研究了它们作为近红外（NIR）探针用于 Aβ 斑块的应用。我们发现，与 Aβ 聚集物的相互作用阻碍了分子转子的旋转自由度，这导致荧光强度显著增强。其中，苯基-吡啶环的探针 4b（K = 8.5 nM）与 Aβ 聚集物结合后荧光强度增加了 98 倍。此外，4b 可以识别转基因（Tg）小鼠和 AD 患者脑切片中的 Aβ 斑块。此外，4b 可以很容易地穿透小鼠的血脑屏障（脑 = 10.11% ID/g）并迅速被冲洗掉。最后，用 Tg 小鼠进行的 NIR 成像证实了 4b 在体内检测 Aβ 斑块的实际应用。总的来说，我们的工作拓宽了 Aβ NIR 探针的研究范围，为 Aβ 检测提供了一种新工具。
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