Polarity-activated super-resolution imaging probe for the formation and morphology of amyloid fibrils
Polarity-activated super-resolution imaging probe for the formation and morphology of amyloid fibrils
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DOI：
10.1007/s12274-020-2899-1
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发表时间：
2020-06-25
期刊：
影响因子：
9.9
通讯作者：
Fu, Hongbing
中科院分区：
文献类型：
--
作者：
Lv, Zheng;Li, Li;Fu, Hongbing
淀粉样斑块的形成通常发生在阿尔茨海默病(AD)的早期阶段。受激发射耗竭(STED)成像为在纳米尺度上可视化淀粉样蛋白结构提供了强有力的工具。然而，许多用于检测淀粉样纤维的商用探针由于其吸收和发射波长不匹配、斯托克斯位移小、易于光漂白等原因不适用于STED成像。在这里，我们展示了一种基于分子内电荷转移供体(D)-PI-受体(A)化合物的极性激活的STED探针。富电子的咔唑基团和贫电子的溴化吡啶基团通过pi共轭的硫代苯桥连在一起，确保了较强的近红外(NIR)发射，斯托克斯位移大于200 nm。与淀粉样蛋白斑块结合前后的微小极性变化导致了从弱发射电荷转移(CT)状态(Phi<；0.04)到高发射局部激发(LE)状态(Phi=0.57)的转变，从而产生了荧光开启探针。该探头具有斯托克斯位移大、光稳定性好、耗尽效率高等优点，在极低的耗尽功率下，实现了淀粉样纤维蛋白玻璃体形成和形态的超分辨成像，横向空间分辨率优于33 nm。此外，还展示了(E)-1-butyl-4(2-(5-(9-ethyl-9H-carbazol-3-yl)thiophen-2-yl)vinyl)溴化吡啶(CTPB)探针在TG小鼠脑片Aβ斑块中的超分辨成像。本研究展示了基于极性-响应机制的淀粉样蛋白超分辨成像探针，为未来淀粉样蛋白探针的发展提供了一种新的途径。
The formation of amyloid plaques usually occurs in the early-stage of Alzheimer's disease (AD). Stimulated emission depletion (STED) imaging provided a powerful tool for visualizing amyloid structures on the nanometer scale. However, many commercial probes adopted in detecting amyloid fibrils are inapplicable to STED imaging, owing to their unmatched absorption and emission wavelengths, small Stokes' shift, easy photo-bleaching, etc. Herein, we demonstrated a polarity-activated STED probe based on an intramolecular charge transfer donor (D)-pi-acceptor (A) compound. The electron-rich carbazole group and the electron-poor pyridinium bromide group, linked by pi-conjugated thiophen-bridge, ensure strong near infrared (NIR) emission with a Stokes' shift larger than 200 nm. The tiny change in polarity before and after binding with amyloid plaques leads to a transition from weakly emission charge-transfer (CT) state (phi< 0.04) to highly emissive locally-excited (LE) state (phi= 0.57), giving rise to a fluorescence Turn-On probe. Together with large Stokes' shift, good photostability and high depletion efficiency, the super-resolution imaging of the formation and morphology of amyloid fibrilsin vitrobased on this probe was realized with a lateral spatial resolution better than 33 nm at an extremely low depletion power. Moreover, theex-vivosuper-resolution imaging of (E)-1-butyl-4(2-(5-(9-ethyl-9H-carbazol-3-yl)thiophen-2-yl)vinyl) pyridinium bromide (CTPB) probe in A beta plaques in the brain slices of a Tg mouse was demonstrated. This research provides a demonstration of the super resolution imaging probe of amyloid fibrils based on polarity-response mechanism, providing a new approach to the development of future amyloid probes.