Harnessing Intramolecular Rotation To Enhance Two-photon Imaging of Aβ Plaques through Minimizing Background Fluorescence

Jinwoo Shin, Peter Verwilst, Hayoung Choi, Sangrim Kang, Jiyou Han, Na Hee Kim, Jin Gyu Choi, Myung Sook Oh, Ji Sun Hwang, Dokyoung Kim, Inhee Mook-Jung, Jong Seung Kim

Research output: Contribution to journalArticlepeer-review

63 Citations (Scopus)

Abstract

The aggregation of amyloid beta (Aβ) proteins in senile plaques is a critical event during the development of Alzheimer's disease, and the postmortem detection of Aβ-rich proteinaceous deposits through fluorescent staining remains one of the most robust diagnostic tools. In animal models, fluorescence imaging can be employed to follow the progression of the disease, and among the different imaging methods, two-photon microscopy (TPM) has emerged as one of the most powerful. To date, several near-infrared-emissive two-photon dyes with a high affinity for Aβ fibrils have been developed, but there has often been a tradeoff between excellent two-photon cross-sections and large fluorescence signal-to-background ratios. In the current work, we introduced a twisted intramolecular charge state (TICT)-based de-excitation pathway, which results in a remarkable fluorescence increase of around 167-fold in the presence of Aβ fibrils, while maintaining an excellent two-photon cross section, thereby enabling high-contrast ex vivo and in vivo TPM imaging. Overall, the results suggest that adopting TICT de-excitation in two-photon fluorophores may represent a general method to overcome the tradeoff between probe brightness and signal-to-background ratio.

Original languageEnglish
Pages (from-to)5648-5652
Number of pages5
JournalAngewandte Chemie - International Edition
Volume58
Issue number17
DOIs
Publication statusPublished - 2019 Apr 16

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (CRI project no. 2018R1A3B1052702, J.S.K.), and the Korea Research Fellowship Program funded by the Ministry of Science and ICT through the NRF of Korea (2016H1D3A1938052, P.V.). This work was also supported by Basic Science Research Program through the NRF of Korea funded by the Ministry of Education (NRF-2018R1A6A1A03025124, NRF-2018R1D1A1B07043383, D.K.; NRF-2017R1D1A1B03032561, P.V.; and NRF-2018R1A2B6002275, J.H.) and by the Bio & Medical Technology Development Program of the NRF of Korea funded by the Ministry of Science and ICT (NRF-2018M3A9H3021707, D.K.), as well as the Brain Research Program (NRF-2015M3C7A1028790, I.M.-J.) through the NRF of Korea. This study was supported by Korea Basic Science Institute Grant (T38662, J.S.K.).

Publisher Copyright:
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

  • Alzheimer's disease
  • fluorescent probes
  • imaging agents
  • molecular rotation
  • two-photon probes

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry

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