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Issue 10, 2014
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Caspase-responsive smart gadolinium-based contrast agent for magnetic resonance imaging of drug-induced apoptosis

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Abstract

Non-invasive detection of caspase-3/7 activity in vivo has provided invaluable predictive information regarding tumor therapeutic efficacy and anti-tumor drug selection. Although a number of caspase-3/7 targeted fluorescence and positron emission tomography (PET) imaging probes have been developed, there is still a lack of gadolinium (Gd)-based magnetic resonance imaging (MRI) probes that enable high spatial resolution detection of caspase-3/7 activity in vivo. Here we employ a self-assembly approach and develop a caspase-3/7 activatable Gd-based MRI probe for monitoring tumor apoptosis in mice. Upon reduction and caspase-3/7 activation, the caspase-sensitive nano-aggregation MR probe (C-SNAM: 1) undergoes biocompatible intramolecular cyclization and subsequent self-assembly into Gd-nanoparticles (GdNPs). This results in enhanced r1 relaxivity—19.0 (post-activation) vs. 10.2 mM−1 s−1 (pre-activation) at 1 T in solution—and prolonged accumulation in chemotherapy-induced apoptotic cells and tumors that express active caspase-3/7. We demonstrate that C-SNAM reports caspase-3/7 activity by generating a significantly brighter T1-weighted MR signal compared to non-treated tumors following intravenous administration of C-SNAM, providing great potential for high-resolution imaging of tumor apoptosis in vivo.

Graphical abstract: Caspase-responsive smart gadolinium-based contrast agent for magnetic resonance imaging of drug-induced apoptosis

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Supplementary files

Article information


Submitted
12 May 2014
Accepted
17 May 2014
First published
03 Jun 2014

Chem. Sci., 2014,5, 3845-3852
Article type
Edge Article
Author version available

Caspase-responsive smart gadolinium-based contrast agent for magnetic resonance imaging of drug-induced apoptosis

D. Ye, A. J. Shuhendler, P. Pandit, K. D. Brewer, S. S. Tee, L. Cui, G. Tikhomirov, B. Rutt and J. Rao, Chem. Sci., 2014, 5, 3845
DOI: 10.1039/C4SC01392A

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