Carboxylesterase-mediated imaging tool for diagnosis of liver injury and surgical resection navigation of pancreatic cancer

The liver and pancreas are both very important digestive and metabolic organs. Once a patient's liver and pancreas show lesions, such as accompanied by tumor proliferation or acute inflammation, their digestive function will be significantly damaged. The malfunction of carboxylesterase (CE) would indicate various metabolic diseases. Monitoring and utilizing the activity changes of CE of liver and pancreas related metabolic diseases will help to discover the pathological mechanisms and interaction between different organs, which would further provide indications for diagnosis and treatment. In this work, we developed a turn-on red fluorescent probe MG-CE with lysosome targeting for CE sensing in vitro and in vivo imaging showed a decrease of CE level in a hepatitis cell model and in non-alcoholic steatohepatitis (NASH) mouse. The fluorescence intensity was higher in pancreatic ductal adenocarcinoma (PDAC) than that in both cancerous and normal cells. Our results show that CE could promote the prodrug irinotecan activation and cause more significant damage to PDAC cells. Therefore, this work would provide a new molecular tool for the diagnostic imaging of NASH and PDAC, which is helpful in understanding the pathogenesis of NASH and the early diagnosis of NASH and PDAC.