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  • br Summary and perspectives In

    2019-09-20


    Summary and perspectives In recent decades, enormous advances have been achieved in the development of enzyme-activatable imaging probes, enabling the accurate detection of enzyme activity in vivo to better understand the biological function of enzymes in disease processes. Activatable probes are characterized by high sensitivity and specificity, which are superior to “always on” probes because the switch from the “off” to “on” state upon interaction with a specific enzyme at the target site allows signal amplification to detect enzyme activity in real time. However, the majority of the currently reported enzyme-activatable probes are only responsive to the hydrolase family (e.g., protease 52., 55., kinase [56]). The design of new activatable imaging probes for the detection of other 2-Arachidonoyl Glycerol clinical of enzymes remains a challenge. However, the continuously emerging strategies (e.g., RIME) will pave the way to design activatable probes for in vivo imaging of protein disulfide isomerase [46] and oxidoreductase 57., 58.. Future advances in the in vivo molecular imaging of enzyme activity will greatly benefit from the progress towards the quantitative detection of enzymes. Quantitative imaging requires knowledge of both the location and concentration of a specific enzyme, which is dependent on the simultaneous measurement of both the product and substrate concentrations at the same location. However, the dynamic in vivo environment presents significant barriers to quantification. Traditional imaging studies are normally dependent on a single imaging modality, which may lead to an inaccurate or even false quantitative results. Therefore, it is necessary to develop new activatable imaging probes with a combination of two or three imaging modalities to provide an additional imaging signal for the quantitative measurement of the probe concentration, independent of enzyme activity [59]. Indeed, the use of a continuous PET signal to correct the MMP activity measured through optical imaging using an MMP-activatable bimodal probe was recently demonstrated, suggesting a high potential for the quantitative measurement of enzyme levels in vivo [60]. Considering the great progress that has been made, we strongly believe that activatable imaging probes will find more applications in clinics, including (i) earlier and more accurate diagnosis of diseases, (ii) imaging-guided surgery, and (iii) real-time assessment of therapeutic efficacy.
    Conflict of interest
    Acknowledgments This work was supported by the National Natural Science Foundation of China (21505070, 21632008) and Natural Foundation of Jiangsu Province (BK20150567).
    Introduction Organophosphorus compounds are a group of highly toxic substances which are extremely applied as pesticides, insecticides and chemical warfare agents [1]. Extensive uses of these compounds enhanced general concerns because of their adverse effects on human health and environment by contamination of soil, sediments and groundwater. Considering the recent progression in bio science, the use of microorganisms for degradation of these toxic substances as an economic and less disruptive way in comparison to other conventional methods would appear to be very interesting [2]. Organophosphorus hydrolase (OPH) (EC 3.1.8.1) is a biocatalyst which is capable to hydrolyze various organophosphorus compounds. However, low thermostability and specification of this enzyme restricted its industrial applications substantially [3]. Therefore, different techniques such as enzyme immobilization are used currently to make the enzyme more stable even under harsh conditions. Immobilization will improve the enzyme characteristics by keeping its natural catalytic surrounding for repeated operations. The immobilized enzymes would have higher endurance in organic solvents and are capable to reuse for several batches of hydrolysis reactions. As well as, in the reactions which are catalyzed by immobilized enzymes in a heterogeneous environment, termination of the reaction is conveniently accessible just by physical isolation of the enzyme from the solution [4], [5]. Numerous methods have been used for enzyme immobilization such as covalent coupling or physical adsorption to a carrier, entrapment in polymeric networks and encapsulation [6], [7]. The immobilization via multipoint tight covalent binding on insoluble matrices will lead to rigidify the tertiary structure of enzymes and has attracted much attention because of its diverse advantages like low enzyme leakage even in severe reaction conditions and efficient usage of bioconjugates in various types of bioreactors. The activity of biocatalyst will decrease during the covalent immobilization, but the consequent remarkable improvement in stability of the enzyme which is immobilized in optimal conditions would overcome this slight enzyme deactivation [8], [9].