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An Unsymmetrical Squaraine-Based Activatable Probe for Imaging Lymphatic Metastasis by Responding to Tumor Hypoxia with MSOT and Aggregation-Enhanced Fluorescent Imaging
Authors:Yi Lin  Lihe Sun  Prof Fang Zeng  Prof Shuizhu Wu
Institution:1. State Key Laboratory of Luminescent Materials and Devices, Key Laboratory of Luminescence from Molecular Aggregates of, Guangdong Province, College of Materials Science and Engineering, South China University of Technology, Wushan Road 381, Guangzhou, 510640 P. R. China

These authors contributed equally to this work.;2. State Key Laboratory of Luminescent Materials and Devices, Key Laboratory of Luminescence from Molecular Aggregates of, Guangdong Province, College of Materials Science and Engineering, South China University of Technology, Wushan Road 381, Guangzhou, 510640 P. R. China

Abstract:Optoacoustic imaging has great potential for preclinical research and clinical practice, and designing robust activatable optoacoustic probes for specific diseases is beneficial for its further development. Herein, an activatable probe has been developed for tumor hypoxia imaging. For this probe, indole and quinoline were linked on each side of an oxocyclobutenolate core to form an unsymmetrical squaraine. A triarylamine group was incorporated to endow the molecule with the aggregation enhanced emission (AEE) properties. In aqueous media, the squaraine chromophore aggregates into the nanoprobe, which specifically responds to nitroreductase and produces strong optoacoustic signals due to its high extinction coefficient, as well as prominent fluorescence emission as a result of its AEE feature. The nanoprobe was used to image tumor metastasis via the lymphatic system both optoacoustically and fluorescently. Moreover, both the fluorescence signals and three-dimensional multispectral optoacoustic tomography signals from the activated nanoprobe allow us to locate the tumor site and to map the metastatic route.
Keywords:aggregation-enhanced emission  fluorescent probes  imaging agents  optoacoustic tomography  squaraines
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