Journal
CHEMICAL SCIENCE
Volume 5, Issue 10, Pages 3845-3852Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c4sc01392a
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Funding
- Stanford University National Cancer Institute (NCI) Centers of Cancer Nanotechnology Excellence [1U54CA151459-01]
- NCI ICMIC@-Stanford [1P50CA114747-06]
- Susan Komen Breast Cancer Foundation
- NIH [R25 CA118681]
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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 r(1) 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 T-1-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.
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