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Article

Simultaneous Monitoring of Multi-Enzyme Activity and Concentration in Tumor Using a Triply Labeled Fluorescent In Vivo Imaging Probe

1
Wyss Institute and Harvard Medical School, Boston, MA 02115, USA
2
Neurochemistry Laboratory, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
3
Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(9), 3068; https://doi.org/10.3390/ijms21093068
Received: 6 April 2020 / Revised: 21 April 2020 / Accepted: 22 April 2020 / Published: 27 April 2020
(This article belongs to the Special Issue Biomarkers for Diagnosis and Prognosis in Urological Tumors)
The use of fluorescent imaging probes that monitor the activity of proteases that experience an increase in expression and activity in tumors is well established. These probes can be conjugated to nanoparticles of iron oxide, creating a multimodal probe serving as both a magnetic resonance imaging (MRI) agent and an indicator of local protease activity. Previous works describe probes for cathepsin D (CatD) and metalloproteinase-2 (MMP2) protease activity grafted to cross-linked iron oxide nanoparticles (CLIO). Herein, we have synthesized a triply labeled fluorescent iron oxide nanoparticle molecular imaging (MI) probe, including an AF750 substrate concentration reporter along with probes for cathepsin B (CatB) sand MMP2 protease activity. The reporter provides a baseline signal from which to compare the activity of the two proteases. The activity of the MI probe was verified through incubation with the proteases and tested in vitro using the human HT29 tumor cell line and in vivo using female nude mice injected with HT29 cells. We found the MI probe had the appropriate specificity to the activity of their respective proteases, and the reporter dye did not activate when incubated in the presence of only MMP2 and CatB. Probe fluorescent activity was confirmed in vitro, and reporter signal activation was also noted. The fluorescent activity was also visible in vivo, with injected HT29 cells exhibiting fluorescence, distinguishing them from the rest of the animal. The reporter signal was also observable in vivo, which allowed the signal intensities of the protease probes to be corrected; this is a unique feature of this MI probe design. View Full-Text
Keywords: cathepsin B; matrix metalloprotease-2; biomarker; near-infrared fluorescent probe; molecular imaging cathepsin B; matrix metalloprotease-2; biomarker; near-infrared fluorescent probe; molecular imaging
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MDPI and ACS Style

Tam, J.; Pilozzi, A.; Mahmood, U.; Huang, X. Simultaneous Monitoring of Multi-Enzyme Activity and Concentration in Tumor Using a Triply Labeled Fluorescent In Vivo Imaging Probe. Int. J. Mol. Sci. 2020, 21, 3068. https://doi.org/10.3390/ijms21093068

AMA Style

Tam J, Pilozzi A, Mahmood U, Huang X. Simultaneous Monitoring of Multi-Enzyme Activity and Concentration in Tumor Using a Triply Labeled Fluorescent In Vivo Imaging Probe. International Journal of Molecular Sciences. 2020; 21(9):3068. https://doi.org/10.3390/ijms21093068

Chicago/Turabian Style

Tam, Jenny, Alexander Pilozzi, Umar Mahmood, and Xudong Huang. 2020. "Simultaneous Monitoring of Multi-Enzyme Activity and Concentration in Tumor Using a Triply Labeled Fluorescent In Vivo Imaging Probe" International Journal of Molecular Sciences 21, no. 9: 3068. https://doi.org/10.3390/ijms21093068

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