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Ratiometric Imaging of MMP‐2 Activity Facilitates Tumor Detection Using Activatable Near‐Infrared Fluorescent Semiconducting Polymer Nanoparticles
Author(s) -
Zeng Wenhui,
Wu Luyan,
Sun Yidan,
Wang Yuqi,
Wang Jinfang,
Ye Deju
Publication year - 2021
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.202101924
Subject(s) - fluorescence , fluorophore , in vivo , fluorescence lifetime imaging microscopy , nanoparticle , biophysics , materials science , preclinical imaging , conjugated system , matrix metalloproteinase , chemistry , near infrared spectroscopy , polymer , nanotechnology , biochemistry , optics , physics , microbiology and biotechnology , composite material , biology
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 α v β 3 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 ( I 690 / I 830 ) 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.