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<p>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, <b>CE-2</b> has been successfully used for high-throughput screening of rapid carboxylesterase inhibitors due to its extremely low detection limit (2.5 × 10<sup>−4</sup> U mL<sup>−1</sup>) and fast recognition ability. <b>CE-3</b> 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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年1月2日

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  • Shuai Huang,
  • Shuaige Bai,
  • Ting Luo,
  • Bin Feng,
  • Min Liu,
  • Fan Zheng,
  • Shuang Huang,
  • Yanpeng Fang,
  • Dan Ding,
  • Wenbin Zeng

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.