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  • Title: Ratiometric Imaging of MMP-2 Activity Facilitates Tumor Detection Using Activatable Near-Infrared Fluorescent Semiconducting Polymer Nanoparticles.
    Author: Zeng W, Wu L, Sun Y, Wang Y, Wang J, Ye D.
    Journal: Small; 2021 Sep; 17(36):e2101924. PubMed ID: 34309199.
    Abstract:
    Enzyme-activatable ratiometric near-infrared (NIR) fluorescent probes enabling noninvasive imaging of enzyme activity in vivo are promising for biomedical research; however, such probes with ratiometric fluorescence emissions both in NIR window under a single NIR light excitation are largely unexplored. Here, a quenched NIR fluorophore of Cy5.5 is integrated with NIR fluorescent poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b']dithiophene)-alt-4,7(2,1,3-benzothiadiazole)] (PCPDTBT)-based semiconducting polymer nanoparticles (SPNs), and an αv β3 integrin-targeting and matrix metalloproteinase-2 (MMP-2)-activatable ratiometric fluorescent probe (SPN-MMP-RGD) is developed. Under excitation at 660 nm, SPN-MMP-RGD shows "always-on" fluorescence of PCPDTBT (830 nm) and activatable fluorescence of Cy5.5 (690 nm) toward MMP-2, affording a remarkable ≈176-fold enhancement in fluorescence intensity ratio between 690 and 830 nm (I690 /I830 ) for sensitive detection of MMP-2 activity in vitro and in tumor cells. By virtue of ratiometric fluorescence imaging independently of probe's concentration, SPN-MMP-RGD can not only accurately report on MMP-2 levels regarding different tumor sizes, but also noninvasively delineate MMP-2-positive tiny gastric tumors metastasis in vivo. The authors' study reveals the potential of SPN-MMP-RGD for ratiometric fluorescence imaging of MMP-2 activity via combining two independent NIR fluorophores, which can be amenable for the design of other enzyme-activatable ratiometric NIR fluorescent probes for reliable in vivo imaging.
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