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)-π-acceptor (A) compound. The electron-rich carbazole group and the electron-poor pyridinium bromide group, linked by π-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 (φ < 0.04) to highly emissive locally-excited (LE) state (φ = 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 fibrils in vitro based on this probe was realized with a lateral spatial resolution better than 33 nm at an extremely low depletion power. Moreover, the ex-vivo super-resolution imaging of (E)-1-butyl-4(2-(5-(9-ethyl-9H-carbazol-3-yl)thiophen-2-yl)vinyl) pyridinium bromide (CTPB) probe in Aβ 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.

淀粉样斑块的形成通常发生在阿尔茨海默氏病（AD）的早期。受激发射损耗（STED）成像提供了一个强大的工具，可以在纳米尺度上可视化淀粉样蛋白结构。然而，由于其无与伦比的吸收和发射波长，小的斯托克斯位移，容易的光漂白等，许多用于检测淀粉样蛋白原纤维的商业探针不适用于STED成像。分子内电荷转移给体（d） - π端受体（A）化合物。通过π连接的富电子咔唑基团和贫电子吡啶鎓溴化物基团共轭噻吩桥，可确保斯托克斯位移大于200 nm的强近红外（NIR）发射。与淀粉样蛋白斑块结合前后极性的微小变化导致从弱发射电荷转移（CT）状态（φ <0.04）转变为高发射局部激​​发（LE）状态（φ = 0.57），从而导致荧光开启探针。结合较大的斯托克斯位移，良好的光稳定性和高耗竭效率，以极低的耗竭功率实现了基于该探针的淀粉样蛋白原纤维形成和形态的体外超分辨率成像，其横向空间分辨率优于33 nm。 。而且，离体（E）-1-丁基-4（2-（5-（9-乙基-9H-咔唑-3-基）噻吩-2-基）乙烯基）溴化吡啶鎓（CTPB）探针在Aβ斑块中的超分辨率成像在Tg小鼠的大脑切片中得到证实。这项研究提供了基于极性响应机制的淀粉样原纤维超分辨率成像探针的演示，为未来的淀粉样探针的开发提供了一种新的方法。