Journal
CHEMICAL SCIENCE
Volume 8, Issue 4, Pages 2723-2728Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c6sc04322d
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Funding
- Singapore NRF Investigatorship [R279-000-444-281]
- National University of Singapore [R279-000-482-133]
- Institute of Materials Research and Engineering of Singapore [IMRE/14-8P1110]
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Direct monitoring of multiple enzyme activities in a given biological process is extremely important for disease diagnosis. Herein, we report a single fluorescent probe that targets two caspase activities in living cells. The probe consists of three parts that includes two AIE fluorogens with distinctive green and red emission colors excitable at a single wavelength, and a hydrophilic peptide as the substrate of the apoptosis initiator caspase-8 and the effector caspase-3. The probe is non-fluorescent in aqueous media. The green and red fluorescence can be sequentially turned on when the peptide substrate is cleaved by the cascade activation of caspase-8 and caspase-3 in early apoptotic HeLa cells induced by hydrogen peroxide. This sequential fluorescence turn-on allows real-time monitoring of the caspase cascade activation during the apoptotic process, which was further explored for evaluating the therapeutic efficiency of anticancer drugs. The probe design strategy developed in this study also proved to be general, which opens a new avenue for real-time, multiplexed imaging of cellular enzyme activity in a biological process.
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