Bivariate tracking of NIR phototherapeutic probe that illuminates the deterioration process of NAFLD-HCC

Non-alcoholic fatty liver disease (NAFLD) has evolved to become a major cause of hepatocellular carcinoma (HCC). Visualization of NAFLD-HCC deterioration process imaging is essential to understand the underlying pathophysiological processes. However, currently relevant probes with short emission wavelengths, univariate and the inability to achieve theranostics functionality have encountered obstacles in further evaluating the NAFLD-HCC process. Here, we present a carboxylesterase (CE)-activated NIR fluorescent probe (BODJ) which has lipid droplets (LDs)-targeting ability and emits at a wavelength of 858 nm with a fluorescence quantum yield of 19.06%. CE-activated BODJ was used as a visual tool to successfully visualize both NAFLD deterioration processes and HCC in situ based on changes in the average number of LDs and the associated fluorescence intensity fluctuations. Imaging results showed that changes associated with CE and LDs in the modelled cells varied during the transition from nonalcoholic fatty liver to nonalcoholic steatohepatitis and later progression to HCC, highlighting the close association between bivariate and disease. We also demonstrate that BODJ has photodynamic (PDT) and photothermal therapy (PTT) capabilities, allowing image-guided dual phototherapy to damage HCC in situ. This NIR probe, which takes advantage of bivariate to track the deterioration process that illuminates NAFLD-HCC and has dual phototherapy capabilities, provides new ideas for the design of probes related to the diagnosis and treatment of hepatic metabolic diseases.