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

• Published in: Chemical science (Cambridge) Vol. 5; no. 10; pp. 3845 - 3852
• Main Authors: Ye, Deju, Shuhendler, Adam J., Pandit, Prachi, Brewer, Kimberly D., Tee, Sui Seng, Cui, Lina, Tikhomirov, Grigory, Rutt, Brian, Rao, Jianghong
• Format: Journal Article
• Language: English
• Published: England 01.01.2014
• Subjects: Apoptosis; Biocompatibility; Biomedical materials; Imaging; Magnetic resonance imaging; Self assembly; Surgical implants; Tumors
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/C4SC01392A

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 .