Ratiometric Imaging of MMP‐2 Activity Facilitates Tumor Detection Using Activatable Near‐Infrared Fluorescent Semiconducting Polymer Nanoparticles

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 αvβ3 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.

Tunning Intermolecular Interaction of Peptide-Conjugated AIEgen in Nano-Confined Space for Quantitative Detection of Tumor Marker Secreted from Cells

“…Moreover, the fluorescence intensity of MP could be gradually increased with an increasing concentration of MMP-2, indicating its potential for the quantitative detection of MMP-2 (Figure G and SI Figure S9). Then, the Michaelis–Menten constant was also calculated ( K m = 13.02 μM) based on a kinetic study on the reaction between MP and MMP-2 (Figure H), suggesting the satisfying binding affinity of MP for MMP-2. − …”

Enhancing the therapeutic efficacy of nanoparticles for cancer treatment using versatile targeted strategies

“…In addition, Zhang’s group synthesized camptothecin-encapsulated mesoporous silica nanoparticles surface functionalized with targeting cRGD and MMP-2 responsive fluorescence imaging groups, acting as a diagnostic platform as well as for tumor location. These advanced nanoplatforms were able to efficiently undergo enzymatic hydrolysis in overexpressed MMP-2 environments to improve tumor treatment by the release of their cargoes [ 236 ]. Further, some amphiphilic block copolymers (such as PCL-PEG) are suitable for the preparation of versatile delivery platforms against cancer.…”

Matrix Metalloproteinases in Helicobacter pylori–Associated Gastritis and Gastric Cancer

“…These sensors can be used for the determination of MMP activity in cell lines and, probably, for in vivo imaging, taking into account their low autofluorescence and high tissue transparency [132]. Since specific MMPs are increased in primary gastric cancer and metastases, the NIR fluorescent probes can be potentially used for a noninvasive detection of tumors localization and size [88,133].…”