An Unsymmetrical Squaraine-based Activatable Probe for Imaging Lymphatic Metastasis through Responding to Tumor Hypoxia by MSOT and Aggregation-enhanced Fluorescent Imaging.

Optoacoustic imaging exhibits 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 oxocyclobutenolate core to form an unsymmetrical squaraine. Triarylamine group was incorporated to afford the aggregation enhanced emission (AEE) property. In aqueous media, the squaraine chromophore aggregates into the nanoprobe which specifically responds to nitroreductase and produce 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 lymphatic system 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 map the metastatic route.