Versatile near-infrared fluorescent probe for in vivo detection of Aβ oligomers |
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| Institution: | 1. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China;2. Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21198, China;3. Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA;1. Faculty of Light Industry and Chemical Engineering, Guangdong University of Technology, Guangdong, 510006, China;2. CNRS, UMR8601, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, CBNIT, Université Paris Descartes, PRES Sorbonne Paris Cité, UFR Biomédicale, 75006, Paris, France;3. Imaging Diagnosis and Interventional Center, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, China;4. Université Paris Diderot, Sorbonne Paris Cité, ITODYS, UMR 7086 CNRS, 75013, Paris, France;5. Laboratoire de Chimie de Coordination du CNRS, 205 Route de Narbonne, 31077, Toulouse Cedex, France;1. Department of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, PR China;2. Qlu School of Medicine, Shandong University, Jinan 502100, PR China;3. Institute of Physical Science and Information Technology, Anhui University, Hefei 230601, PR China;1. Key Laboratory for Advanced Materials & Institute of Fine Chemicals, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237, PR China;2. National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), 189 Guo Shoujing Rd., Shanghai 201203, PR China;3. CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China |
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| Abstract: | Amyloid-β oligomers (AβOs) enrichment in brain is highly related to Alzheimer’s pathogenesis, but tracing them in the brain by imaging technique is still a great challenge due to their heterogeneity and metastability. Herein, a new near-infrared (NIR) fluorescent probe, namely, PTO-41, was designed and synthesized to specifically target AβOs. PTO-41 possesses excellent functional properties including optimal fluorescent properties (emission maxima at 680 nm upon interacting with AβOs), high affinity (Kd = 349 nM), low cell toxicity, desirable lipophilicity (log P = 2.24), and fast wash out from the brain (brain2 min/brain60 min = 5.0). Furthermore, PTO-41 exhibits a high sensitivity toward AβOs in vitro phantom imaging experiments. More importantly, PTO-41 shows great capacity to differentiate between 4-month-old APP/PS1 model mice from age-matched control mice using in vivo imaging. In summary, PTO-41 almost meets all the requirements as a versatile NIR fluorescent probe for the detection of AβOs both in vitro and in vivo. |
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| Keywords: | Amyloid-β oligomers Alzheimer’s disease Near-infrared fluorescent probe |
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