한빛사 논문
Jinwoo Shin,[a]‡ Peter Verwilst,[a]‡ Hayoung Choi,[b]‡ Sangrim Kang,[c,d] Jiyou Han,[e] Na Hee Kim,[f] Jin GyuChoi,[g] Myung Sook Oh,[g] Ji Sun Hwang,[i] Dokyoung Kim, *[c,f,h] Inhee Mook-Jung,*[b] and Jong Seung Kim*[a]
[a] Department of Chemistry, Korea UniversitySeoul 02841 (Korea)
[b] Department of Biochemistry and Biomedical Sciences, College of Medicine, Seoul National University, Seoul 03080 (Korea)
[c] Department of Anatomy and Neurobiology, College of Medicine
[d] Department of Pathology, College of Medicine
[f] Department of Biomedical Science, Graduate School
[g] Department of Life and Nanopharmaceutical Sciences
[h] Biomedical Science Institute, Kyung Hee UniversitySeoul 02447 (Korea)
[e] Department of Biological SciencesLaboratory of Stem Cell Research and Biotechnology, Hyupsung University, Hwasung-si 18330 (Korea)
[i] Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), Daegu 41061 (Korea)
‡ These authors contributed equally
*To whom correspondence should be addressed.
Abstract
The aggregation of 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 via 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 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 TICT‐based de‐excitation pathway, resulting in a remarkable fluorescence increase of ~167‐fold in the presence of Aβ‐fibrils, while maintaining an excellent two‐photon cross section, allowing 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 probe brightness vs. probe signal to background tradeoff.
Keywords: Imaging agents, Fluorescent probes, Two-Photon probes, Molecular rotation, Alzheimer's disease
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