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Harnessing Intramolecular Rotation To Enhance Two‐photon Imaging of Aβ Plaques through Minimizing Background Fluorescence
Author(s) -
Shin Jinwoo,
Verwilst Peter,
Choi Hayoung,
Kang Sangrim,
Han Jiyou,
Kim Na Hee,
Choi Jin Gyu,
Oh Myung Sook,
Hwang Ji Sun,
Kim Dokyoung,
MookJung Inhee,
Kim Jong Seung
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201900549
Subject(s) - fluorescence , two photon excitation microscopy , fluorescence lifetime imaging microscopy , biophysics , chemistry , intramolecular force , microscopy , ex vivo , in vivo , preclinical imaging , fluorescence microscope , nuclear magnetic resonance , photochemistry , optics , physics , biology , in vitro , microbiology and biotechnology , stereochemistry , biochemistry
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.