Cathepsin B-Activated Fluorescent and Photoacoustic Imaging of Tumor,Analytical Chemistry

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Cathepsin B-Activated Fluorescent and Photoacoustic Imaging of Tumor
Analytical Chemistry ( IF 6.7 ) Pub Date : 2021-06-28 , DOI: 10.1021/acs.analchem.1c02145
Xiaoxia Chen ₁ , Xingxing Ren ₂ , Yuhan Zhu ₁ , Ziyan Fan ₁ , Lele Zhang ₁ , Zhengjie Liu ₁ , Ling Dong ₃ , Zijuan Hai ₁

Affiliation

Early diagnosis is crucial to the treatment of cancer. Cathepsin B (CTB) plays an important role in numerous cancers, which is a promising biomarker for early diagnosis of cancer. It is necessary to exploit new probes for visualization of CTB in vivo. Fluorescent/photoacoustic (FL/PA) imaging is a powerful tool for in vivo study which possesses both excellent sensitivity and spatial resolution. To our knowledge, there has been no FL/PA probe to image CTB in vitro or in vivo. Therefore, we developed two CTB-activated FL/PA probes HCy-Cit-Val and HCy-Gly-Leu-Phe-Gly, which could successfully monitor CTB activity in vivo. Both two probes had excellent sensitivity and selectivity in vitro. Cell imaging showed that HCy-Cit-Val or HCy-Gly-Leu-Phe-Gly could image endogenous CTB in lysosome with 6.8-fold or 5.1-fold enhancement of the FL signal and 5.8-fold or 3.4-fold enhancement of the PA signal compared to their inhibitor contrast groups. Tumor imaging in vivo further confirmed the good applicability of these two probes to monitor CTB activity with high sensitivity and spatial resolution. Moreover, the property of HCy-Cit-Val is superior to HCy-Gly-Leu-Phe-Gly due to the higher catalytic efficiency of CTB toward HCy-Cit-Val than HCy-Gly-Leu-Phe-Gly. We envision that our FL/PA probe HCy-Cit-Val will be suitable for clinical early diagnosis of CTB-related cancer in the near future.

中文翻译：

组织蛋白酶 B 激活的肿瘤荧光和光声成像

早期诊断对于癌症的治疗至关重要。组织蛋白酶 B (CTB) 在多种癌症中发挥着重要作用，它是一种很有前途的癌症早期诊断生物标志物。有必要开发用于体内CTB 可视化的新探针。荧光/光声 (FL/PA) 成像是一种强大的体内研究工具，具有出色的灵敏度和空间分辨率。据我们所知，还没有 FL/PA 探针在体外或体内成像 CTB 。因此，我们开发了两种 CTB 激活的 FL/PA 探针HCy-Cit-Val和HCy-Gly-Leu-Phe-Gly，它们可以成功地监测 CTB体内活性. 两种探针在体外均具有极好的灵敏度和选择性。细胞成像显示HCy-Cit-Val或HCy-Gly-Leu-Phe-Gly可以对溶酶体中的内源性 CTB 成像，FL 信号增强 6.8 倍或 5.1 倍，PA 增强 5.8 倍或 3.4 倍信号与其抑制剂对照组相比。体内肿瘤成像进一步证实了这两种探针在以高灵敏度和空间分辨率监测 CTB 活动方面的良好适用性。此外，的属性HCY-CIT-VAL优于HCY -甘氨酸-亮氨酸-苯丙氨酸-甘氨酸由于朝向CTB的较高的催化效率HCY-CIT-VAL比HCY -甘氨酸-亮氨酸-苯丙氨酸-甘氨酸. 我们设想我们的 FL/PA 探针HCy-Cit-Val在不久的将来将适用于 CTB 相关癌症的临床早期诊断。

更新日期：2021-07-13

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