期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 141, 期 15, 页码 6224-6233出版社
AMER CHEMICAL SOC
DOI: 10.1021/jacs.8b13376
关键词
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资金
- NIH [P30CA060553]
- Fondazione Cassa di Risparmio di Firenze
- COST Action [CA15209]
- NCI CCSG [P30 CA060553]
- NASA Ames Research Center [NNA06CB93G]
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.
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