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Engineering of donor-acceptor-donor curcumin analogues as near-infrared fluorescent probes for in vivo imaging of amyloid-beta species

文献类型：期刊论文

作者Fang, Daqing2,3; Wen, Xidan1; Wang, Yuqi1; Sun, Yidan1; An, Ruibing1; Zhou, Yu3; Ye, Deju1; Liu, Hong2,3
刊名THERANOSTICS
出版日期2022
卷号12期号:7页码:3178-3195
关键词Alzheimer's disease Amyloid-beta NIR fluorescence probe in vivo imaging D-A-D molecules
ISSN号1838-7640
DOI10.7150/thno.68679
通讯作者Ye, Deju(dejuye@nju.edu.cn) ; Liu, Hong(hliu@simm.ac.cn)
英文摘要Near-infrared (NIR) fluorescent imaging of both soluble and insoluble A beta species in the brain of Alzheimer's disease (AD) is crucial for the early diagnosis and intervention of AD. To date, a variety of NIR fluorescent probes have been reported for the detection of A beta species. Among these probes, CRANAD-58 was reported to have the capability to detect both soluble and insoluble A beta species, which is vital to monitor the changes of A beta species during the pathological course of the disease. Though CRANAD-58 has shown promise to noninvasively detect A beta species in transgenic AD mice, the emission wavelength (similar to 670 nm) is still too short for further applications. Therefore, new probes with longer emission wavelength and improved physiological properties are in highly demand. Herein, we report the design and engineering of nine donor-acceptor-donor molecules as "off-on" near-infrared fluorescent probes for in vivo imaging of both soluble and insoluble A beta species in living AD mice owing to its improved in vitro properties and in vivo performance. Methods: We report a two-round strategy to develop nine "off-on" NIR fluorescence probes via structural modification of a curcumin analogue-based donor-acceptor-donor architecture. In round one, probes 1 and 2 were synthesized, and probe 2 was identified to be an optimum probe as it showed distinct "off-on" NIR fluorescence at > 690 nm upon binding to A beta monomers, oligomers and aggregates. To further improve the in vivo performance, further structural modification of probe 2 into probes 3-9 was then conducted. The fluorescence response with A beta species and histological staining in vitro and in vivo imaging of A beta species in APP/PS1 transgenic AD mice and age-matched wild-type mice were performed. Results: We demonstrate that, compared to probe 2, probe 9 with improved physiological properties hold the fastest kinetics (similar to 10 min) to produce not only higher brain fluorescence intensity in 10-month-old APP/PS1 transgenic AD mice, but also afford a higher discrepancy in brain fluorescence to discriminate AD mice from wild-type (WT) mice. Probe 9 also hold the ability to detect soluble A beta species in 6-month-old APP/PS1 transgenic mice. Probe 9 was further applied for dynamic visualization of A beta plaques in a skull-thinning 14-month-old APP/PS1 mouse, which revealed its immediate penetration into brain parenchyma and selective labeling of both parenchymal and angiopathic A beta plaques. In addition, probe 9 possessed significantly high attenuation effect on the aggregation of A beta monomers. Conclusion: Our results demonstrate the good potential of probe 9 for longitudinal NIR fluorescence imaging of soluble and insoluble A beta species in APP/PS1 transgenic AD mice, which may act as a useful tool for early diagnosis and intervention of AD.
WOS关键词ALZHEIMERS-DISEASE ; CROSS-LINKING ; PLAQUES ; OLIGOMERS ; BRAIN ; NEURODEGENERATION ; DEPOSITS ; DESIGN ; MODELS ; DYES
资助项目National Natural Science Foundation of China[21632008] ; National Natural Science Foundation of China[21922406] ; Natural Science Foundation of Jiangsu Province[BK20190055] ; Excellent Research Program of Nanjing University[ZYJH004]
WOS研究方向Research & Experimental Medicine
语种英语
WOS记录号WOS:000786579800010
出版者IVYSPRING INT PUBL
源URL[http://119.78.100.183/handle/2S10ELR8/299541]  
专题新药研究国家重点实验室
通讯作者Ye, Deju; Liu, Hong
作者单位1.Nanjing Univ, Chem & Biomed Innovat Ctr ChemB, Sch Chem & Chem Engn, State Key Lab Analyt Chem Life Sci, Nanjing 210023, Peoples R China
2.Shenyang Pharmaceut Univ, Key Lab Struct Based Drug Design & Discovery, Minist Educ, Shenyang 110016, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Fang, Daqing,Wen, Xidan,Wang, Yuqi,et al. Engineering of donor-acceptor-donor curcumin analogues as near-infrared fluorescent probes for in vivo imaging of amyloid-beta species[J]. THERANOSTICS,2022,12(7):3178-3195.
APA Fang, Daqing.,Wen, Xidan.,Wang, Yuqi.,Sun, Yidan.,An, Ruibing.,...&Liu, Hong.(2022).Engineering of donor-acceptor-donor curcumin analogues as near-infrared fluorescent probes for in vivo imaging of amyloid-beta species.THERANOSTICS,12(7),3178-3195.
MLA Fang, Daqing,et al."Engineering of donor-acceptor-donor curcumin analogues as near-infrared fluorescent probes for in vivo imaging of amyloid-beta species".THERANOSTICS 12.7(2022):3178-3195.

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来源：上海药物研究所

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