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In situ imaging of aminopeptidase N activity in hepatocellular carcinoma: a migration model for tumour using an activatable two-photon NIR fluorescent probe†
Chemical Science ( IF 7.6 ) Pub Date : 2018-11-27 00:00:00 , DOI: 10.1039/c8sc04685a Haidong Li 1 , Yueqing Li 2 , Qichao Yao 1 , Jiangli Fan 1, 3 , Wen Sun 1, 3 , Saran Long 1, 3 , Kun Shao 1, 3 , Jianjun Du 1 , Jingyun Wang 3, 4 , Xiaojun Peng 1, 3
Chemical Science ( IF 7.6 ) Pub Date : 2018-11-27 00:00:00 , DOI: 10.1039/c8sc04685a Haidong Li 1 , Yueqing Li 2 , Qichao Yao 1 , Jiangli Fan 1, 3 , Wen Sun 1, 3 , Saran Long 1, 3 , Kun Shao 1, 3 , Jianjun Du 1 , Jingyun Wang 3, 4 , Xiaojun Peng 1, 3
Affiliation
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CD13/aminopeptidase N (APN), which is a zinc-dependent metalloproteinase, plays a vital role in the growth, migration, angiogenesis, and metastasis of tumours. Thus, in situ molecular imaging of endogenous APN levels is considerably significant for investigating APN and its different functions. In this study, a novel two-photon near-infrared (NIR) fluorescence probe DCM-APN was prepared to perform in vitro and in vivo tracking of APN. The N-terminal alanyl site of probe DCM-APN was accurately hydrolysed to the amino group, thereby liberating strong fluorescence owing to the recovery of the Intramolecular Charge Transfer (ICT) effect. By considering its outstanding selectivity, ultra-sensitivity (DL 0.25 ng mL−1) and favourable biocompatibility, the probe DCM-APN was used to distinguish between normal cells (LO2 cells) and cancer cells (HepG-2 and B16/BL6 cells). Furthermore, migration of hepatocellular carcinoma cells was apparently inhibited by ensuring that the APN catalytic cavity was occupied by bestatin. The identification of three-dimensional (3D) fluorescence in cancer tissues was completed under two-photon excitation coupled with lighting up hepatocellular carcinoma tumours in situ; this revealed that probe DCM-APN is an effective tool for detecting APN, thereby assisting in the early diagnosis of tumour in clinical medicine.
中文翻译：
肝细胞癌中氨肽酶 N 活性的原位成像：使用可激活双光子 NIR 荧光探针的肿瘤迁移模型†
CD13/氨肽酶N（APN）是一种锌依赖性金属蛋白酶，在肿瘤的生长、迁移、血管生成和转移中发挥着至关重要的作用。因此，内源性APN 水平的原位分子成像对于研究 APN 及其不同功能具有相当重要的意义。本研究制备了一种新型双光子近红外（NIR）荧光探针DCM-APN，用于APN的体外和体内跟踪。探针DCM-APN的N端丙氨酰位点被准确地水解为氨基，从而由于分子内电荷转移（ICT）效应的恢复而释放出强荧光。考虑到其出色的选择性、超灵敏性（DL 0.25 ng mL -1）和良好的生物相容性，探针DCM-APN用于区分正常细胞（LO2细胞）和癌细胞（HepG-2和B16/BL6细胞） 。此外，通过确保APN催化腔被贝他汀占据，肝细胞癌细胞的迁移明显受到抑制。在双光子激发结合原位点亮肝细胞癌肿瘤的情况下完成了癌组织中三维（3D）荧光的识别；这表明探针DCM-APN是检测APN的有效工具，从而辅助临床医学中肿瘤的早期诊断。
更新日期：2018-11-27
中文翻译：
肝细胞癌中氨肽酶 N 活性的原位成像：使用可激活双光子 NIR 荧光探针的肿瘤迁移模型†
CD13/氨肽酶N（APN）是一种锌依赖性金属蛋白酶，在肿瘤的生长、迁移、血管生成和转移中发挥着至关重要的作用。因此，内源性APN 水平的原位分子成像对于研究 APN 及其不同功能具有相当重要的意义。本研究制备了一种新型双光子近红外（NIR）荧光探针DCM-APN，用于APN的体外和体内跟踪。探针DCM-APN的N端丙氨酰位点被准确地水解为氨基，从而由于分子内电荷转移（ICT）效应的恢复而释放出强荧光。考虑到其出色的选择性、超灵敏性（DL 0.25 ng mL -1）和良好的生物相容性，探针DCM-APN用于区分正常细胞（LO2细胞）和癌细胞（HepG-2和B16/BL6细胞） 。此外，通过确保APN催化腔被贝他汀占据，肝细胞癌细胞的迁移明显受到抑制。在双光子激发结合原位点亮肝细胞癌肿瘤的情况下完成了癌组织中三维（3D）荧光的识别；这表明探针DCM-APN是检测APN的有效工具，从而辅助临床医学中肿瘤的早期诊断。
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