An enzyme activated fluorescent probe for LTA₄H activity sensing and its application in cancer screening

Early diagnosis of cancer is an efficient strategy to prevent tumor progression and improve the survival rate of patients. However, to discovery of reliable tumor-specific biomarkers remains a great challenge. Leukotriene A4 hydrolase (LTA₄H) is a bifunctional zinc metalloenzyme with epoxide hydrolase activity and aminopeptidase activity, which plays important roles in allergic and inflammatory reactions and showed strong relevance with carcinoma progression. We thus sought to investigate the possibility of application LTA₄H activity detection in cancer diagnosis. To achieve this, we herein develop an enzyme activated fluorescent probe for LTA₄H activity sensing by incorporating the specific recognition unit of LTA₄H with a red-emitting fluorophore. The acquired probe (named as ADMAB) showed high sensitivity and specificity toward LTA₄H in vitro. By further application of ADMAB in living cells, significantly elevated LTA₄H activity in cancer cell lines was observed when compared with normal cell lines and in vivo tracing A549 tumor in nude mice was also realized by ADMAB. Meanwhile, the wound-healing assay further revealed the importance of LTA₄H in tumor metastasis. Moreover, the LTA₄H activity in human serum sample was successfully detected by ADMAB and significantly elevated LTA₄H activity in patients diagnosed with cancer was firstly found, which demonstrated ADMAB to be a useful tool for cancer diagnosis and LTA₄H related biological study.