Polarity-activated super-resolution imaging probe for the formation and morphology of amyloid fibrils

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.