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

Abstract

Simultaneous detection of different diseases via a single fluorophore is challenging. We herein report a bichromatic fluorophore named <b>Cy-914</b> 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. <b>Cy-914</b> with a p<i>K</i>_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, <b>Cy-914</b> 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.