Abstract
Enzyme-activated probes enable complex biological processes to be studied in real-time. A wide range of enzymes are modulated in diseases, including cancer, inflammatory diseases and cardiovascular disease, and have the potential to act as vital diagnostic and prognostic biomarkers to monitor and report on disease progression. In this perspective article, we discuss suitable design characteristics of enzyme-activated fluorescent probes for ex vivo and in vivo optical imaging applications. With a particular focus on atherosclerosis imaging, we highlight recent approaches to report on the activity of cathepsins (K and B), matrix metalloproteinases (MMP-2 and MMP-9), thrombin, heme oxygenase-1 (HO-1) and myeloperoxidase (MPO).
Highlights
Optical Imaging (OI) is a powerful, highly sensitive and cost effective non-invasive diagnostic technique routinely used in chemical biology.1 ‘Activity’ or ‘smart’ fluorescent probes are highly advantageous for use in OI, and typically display a rapid and selective fluorescence activation mechanism resulting in a high signal-to-noise ratio against the background signal
Using recent approaches from the literature, we have summarised the desirable design considerations and activation mechanisms for enzyme-activatable probes in OI applications
It remains key that new probes are developed in the future to ensure vascular diseases are detected earlier and more efficiently, before the onset of severe complications
Summary
Optical Imaging (OI) is a powerful, highly sensitive and cost effective non-invasive diagnostic technique routinely used in chemical biology.1 ‘Activity’ or ‘smart’ fluorescent probes are highly advantageous for use in OI, and typically display a rapid and selective fluorescence activation mechanism resulting in a high signal-to-noise ratio against the background signal. One of the key processes in disruption is intraplaque hemorrhage (IPH), a bleed within the plaque itself, and strongly associated with more complete plaque disruption causing thrombosis and blockage of the lumen.[13,14] atherosclerosis is accelerated by IPH, and often results in the onset of ischemic stroke and myocardial infarction.[15] In contrast, stable plaques display the opposite features and are significantly less prone to rupture In this perspective, we summarise the design aims and activation mechanisms that may guide the future development of enzyme-activated probes for disease diagnosis and prognosis. Chemical probes for other biological targets secreted by macrophages, such as cytokines, will not be discussed
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