Cathepsin B-Activated Fluorescent and Photoacoustic Imaging of Tumor

Abstract

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 CTBin vivo. Fluorescent/photoacoustic (FL/PA) imaging is a powerful tool forin vivostudy which possesses both excellent sensitivity and spatial resolution. To our knowledge, there has been no FL/PA probe to image CTBin vitroorin vivo. Therefore, we developed two CTB-activated FL/PA probesHCy-Cit-ValandHCy-Gly-Leu-Phe-Gly, which could successfully monitor CTB activityin vivo. Both two probes had excellent sensitivity and selectivityin vitro. Cell imaging showed thatHCy-Cit-ValorHCy-Gly-Leu-Phe-Glycould 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 imagingin vivofurther confirmed the good applicability of these two probes to monitor CTB activity with high sensitivity and spatial resolution. Moreover, the property ofHCy-Cit-Valis superior toHCy-Gly-Leu-Phe-Glydue to the higher catalytic efficiency of CTB towardHCy-Cit-ValthanHCy-Gly-Leu-Phe-Gly. We envision that our FL/PA probeHCy-Cit-Valwill be suitable for clinical early diagnosis of CTB-related cancer in the near future.