Bichromatic Imaging with Hemicyanine Fluorophores Enables Simultaneous Visualization of Non-alcoholic Fatty Liver Disease and Metastatic Intestinal Cancer

Simultaneous detection of different diseases via a single fluorophore is challenging. We herein report a bichromatic fluorophore named Cy-914 for the simultaneous diagnosis of non-alcoholic fatty liver disease (NAFLD) and metastatic intestinal cancer by leveraging its NIR-I/NIR-II dual-color imaging capability. Cy-914 with a pK(a) of 6.98 exhibits high sensitivity to pH and viscosity, showing turn-on NIR-I fluorescence at 795 nm in an acidic tumor microenvironment, meanwhile displaying intense NIR-II fluorescence at 914/1030 nm under neutral to slightly basic viscous conditions. Notably, Cy-914 could sensitively and noninvasively monitor viscosity variations in the progression of NAFLD. More importantly, it was able to simultaneously visualize NAFLD (ex/em = 808/1000-1700 nm) and intestinal metastases (ex/em = 570/810-875 nm) in two independent channels without spectral cross interference after topical spraying, further improving fluorescence-guided surgery of tiny metastases less than 3 mm. This strategy may provide an understanding for developing multi-color fluorophores for multi-disease diagnosis.

Automated summary

In this study, a bichromatic fluorophore called Cy-914 was developed for the simultaneous diagnosis of NAFLD and metastatic intestinal cancer. Cy-914 showed different fluorescence signals at different wavelengths under acidic and neutral to slightly basic viscous conditions, and could monitor the progression of NAFLD. By visualizing different diseases in independent channels, this fluorophore improved fluorescence-guided surgery.