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Bimodal Fluorescence-Magnetic Resonance Contrast Agent for Apoptosis Imaging
journal contribution
posted on 2019-03-28, 00:00 authored by Hao Li, Giacomo Parigi, Claudio Luchinat, Thomas J. MeadeEffective 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.
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CP 1MR signal enhancementBimodal Fluorescence-Magnetic Resonance Contrast AgentDEVDaggregation-driven FL-MR probe designprobe design platformFL-MR turn-on responseapoptosiMR signal quantificationbimodal fluorescence-magnetic resonancemultimodal molecular imagingcancer therapy responsecaspase probe 1
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