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Research Article

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

Zheng Lv1,2,§, Li Li1,§, Zhongwei Man1, Zhenzhen Xu1( ), Hongtu Cui3, Rui Zhan3, Qihua He3, Lemin Zheng3,4 ( ), Hongbing Fu1,2( )
Beijing Key Laboratory for Optical Materials and Photonic Devices, Capital Normal University, Beijing 100048, China
Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Institute of Molecular Plus, Tianjin University, Tianjin 300072, China
The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Health Science Center, Peking University, Beijing 100191, China
China National Clinical Research Center for Neurological Diseases, Tiantan Hospital, Advanced Innovation Center for Human Brain Protection, The Capital Medical University, Beijing 100050, China

§ Zheng Lv and Li Li contributed equally to this work.

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Abstract

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.

Keywords

polarity-activatedamyloid fibrilssuper-resolution imagingcharge transfernear infrared (NIR) emission

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Nano Research
Volume 13 Issue 9,
September 2020
Pages 2556-2563
DOI: 10.1007/s12274-020-2899-1
Cite this article:
Lv Z, Li L, Man Z, et al. Polarity-activated super-resolution imaging probe for the formation and morphology of amyloid fibrils. Nano Research, 2020, 13(9): 2556-2563. https://doi.org/10.1007/s12274-020-2899-1
Topics:
Infrared devices MorphologyProbes

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Received: 26 March 2020
Revised: 21 May 2020
Accepted: 22 May 2020
Published: 25 June 2020
© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020
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