Engineering high-performance chemiluminescent probes via enzymatic pocket targeting:high-throughput screening for ultralong afterglow imaging of orthotopic hepatocellular carcinoma  

作　　者：Shuai Huang Shuaige Bai Ting Luo Bin Feng Min Liu Fan Zheng Shuang Huang Yanpeng Fang Dan Ding Wenbin Zeng 

机构地区：[1]Xiangya School of Pharmaceutical Sciences,Central South University,Changsha 410013,China [2]College of Life Sciences,Nankai University,Tianjin 300011,China

出　　处：《Science China Chemistry》2025年第3期1175-1184,共10页中国科学(化学英文版)

基　　金：supported by the National Natural Science Foundation of China (82272067,22107123,and M-0696);the Natural Science Foundation of Hunan Province (2022JJ80052)。

摘　　要：Hepatocellular carcinoma(HCC)is a highly aggressive liver malignancy and the main form of liver cancer.Early diagnosis and treatment of HCC can effectively reduce mortality.Carboxylesterase(CE)-specific detection and imaging can be used for early diagnosis and image-guided surgical of HCC.However,traditional optical probes suffer from poor selectivity and low imaging signal-to-noise ratio.Here,we have constructed a series of chemiluminescent probes for carboxylesterase detection based on the strategy of enzymatic pocket-oriented steric tailoring techniques.The probes with different unique and excellent properties have been obtained through the structure-based steric hindrance adjustment on the recognition site.Here,CE-2 has been successfully used for high-throughput screening of rapid carboxylesterase inhibitors due to its extremely low detection limit(2.5×10^(-4)U mL^(-1))and fast recognition ability.CE-3 has been successfully used for image-guided surgery of orthotopic hepatocellular carcinoma due to its ultra-long chemiluminescence imaging(over 12 h)of hepatocellular carcinoma.This study may promote advances in the rapid detection and screening of inhibitory drugs for CE and the field of surgical navigation in HCC.

关 键 词：chemiluminescent probes CARBOXYLESTERASE high-throughput inhibitor screening long-lived chemiluminescent image image-guided surgery 

分 类 号：R735.7[医药卫生—肿瘤] O657.3[医药卫生—临床医学]