Bimodal Fluorescence-Magnetic Resonance Contrast Agent for Apoptosis Imaging

Abstract

Effective cancer therapy largely depends on inducing apoptosis in cancer cells via chemotherapy and/or radiation. Monitoring apoptosis in real-time provides invaluable information for evaluating cancer therapy response and screening preclinical anticancer drugs. In this work, we describe the design, synthesis, characterization and in vitro evaluation of caspase probe 1 (CP1), a bimodal fluorescence-magnetic resonance (FL-MR) probe that exhibits simultaneous FL-MR turn-on response to caspase-3/7. Both caspases exist as inactive zymogens in normal cells but are activated during apoptosis and are unique biomarkers for this process. CP1 has three distinct components: a DOTA-Gd(III) chelate that provides the MR signal enhancement, tetraphenylethylene as the aggregation induced emission luminogen (AIEgen), and DEVD peptide which is a substrate for caspase-3/7. In response to caspase-3/7, the water-soluble peptide DEVD is cleaved and the remaining Gd(III)-AIEgen (Gad-AIE) conjugate aggregates leading to increased FL-MR signals. CP1 exhibited sensitive and selective dual FL-MR turn-on response to caspase-3/7 in vitro and was successfully tested by fluorescence imaging of apoptotic cells. Remarkably, we were able to use the FL response of CP1 to quantify the exact concentrations of inactive and active agents and accurately predict the MR signal in vitro. We have demonstrated that the aggregation-driven FL-MR probe design is a unique method for MR signal quantification. This probe design platform can be adapted for a variety of different imaging targets, opening new and exciting avenues for multimodal molecular imaging.

Fluorescent probes for organelle-targeted bioactive species imaging

“…The advancement of microscopic imaging technology has introduced new opportunities for visualizing subtle intracellular structures. To investigate the critical events in living cells on the organelle and even more subtle levels, elaborately designed fluorescent probes are indispensable 15. Currently, benefiting from their easy design, preparation and functionalization, fluorescent molecular and nanoprobes are being widely employed for biological imaging 1a,b,f,2c.…”

Simultaneous detection of small molecule thiols with a simple 19F NMR platform

“…We believed that this method could easily detect other kinds of enzyme activities by rational fusion of Cys (Cys-Py 4F ) into recognition sequences. [40][41][42]…”

Internally Responsive Nanomaterials for Activatable Multimodal Imaging of Cancer

“…Meade and co‐workers prepared a caspase‐3/7 activatable FL/MR contrast agent where both signals were enhanced after activation. [ 73 ] This fluorogenic caspase probe (CP1) combined a Gd 3+ ‐chelate, a tetraphenylethylene unit for aggregation‐induced emission luminogen (AIEgen), and a caspase‐3/7 cleavable substrate (DEVD peptide). Once the DVED peptide is cleaved by caspase‐3/7, the remaining Gd 3+ ‐chelate‐AIEgen moieties aggregated together.…”