Abstract
Proteases are enzymes capable of catalyzing protein breakdown, which is critical across many biological processes. There are several families of proteases, each of which perform key functions through the degradation of specific proteins. As our understanding of cancer improves, it has been demonstrated that several proteases can be overactivated during the progression of cancer and contribute to malignancy. Optical imaging systems that employ near-infrared (NIR) fluorescent probes to detect protease activity offer clinical promise, both for early detection of cancer as well as for the assessment of personalized therapy. In this Review, we review the design of NIR probes and their successful application for the detection of different cancer-associated proteases.
Highlights
The ability to acquire images in vivo in intact organisms provides a wealth of physiological and pathological information that is not available when analyzing cells or tissues ex vivo
On a more mechanistic level, biomedical imaging can serve as a tool for translating clinically relevant animal models of cancer into human studies.[1−4] Currently, clinical imaging is mostly derived from computed tomography (CT), magnetic resonance imaging (MRI),[5,6] positron emission tomography (PET),[7] and single-photon emission computed tomography (SPECT).[8]
Proteases are interesting targets for activatable NIR probes, an alternative class of fluorophores which change their spectral properties upon target engagement, because they can be designed to react with specific enzymes.[23−25] Activatable probes featuring specific peptide sequences can be tailored to individual proteases so that enzymatic activities within tumors can be monitored by their fluorescence readouts (Figure 1)
Summary
The ability to acquire images in vivo in intact organisms provides a wealth of physiological and pathological information that is not available when analyzing cells or tissues ex vivo. Upon peptide cleavage by cathepsin B, the FRET effect was reduced, and the enzyme activity was detectable by fluorescence while the photodynamic illumination at 808 nm led to cancer cell death in vivo in mouse models
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