A simple “spraying” fluorescence-guided surgery by AIE probes for liver tumor resection through configuration-induced cross-identification

Surgical resection is the preferred option for hepatocellular carcinoma (HCC), but surgical navigation technology using indocyanine green still has some drawbacks such as non-specific imaging, thus it is very important to develop new fluorescence imaging technology. All-cis hexaphenyl-1,3-butadiene derivative (ZZ-HPB-NC) with aggregation-induced emission (AIE) feature has been reported to be quickly turned-on fluorescent response in the intraoperative frozen-section slides of HCC. However, the probe did not respond to normal liver tissue around HCC. In order to enhance the diagnostic rate and elucidate the response mechanism, all-trans configuration EE-HPB-NC, was furtherly synthesized. Within two minutes, non-cancer tissues could be fluorescently labeled by EE-HPB-NC by spraying, showing the same effect with ZZ-HPB-NC to HCC. The results indicated that the configuration-induced cross-identification fluorescence imaging strategy was achieved through the combination of ZZ- and EE-HPB-NC. Then the mechanism of HPB-NC localization in HCC lesions was explored, and the binding of HPB-NC with specific proteins in cells resulted in the AIE effect to label HCC cells. On this basis, the accuracy of specific fluorescence imaging for HCC was further verified on the mouse hepatic neoplasm models, indicating that it has clinical application potential for surgical fluorescence real-time navigation.