Real-time monitoring of cell apoptosis and drug screening using fluorescent light-up probe with aggregation-induced emission characteristics

• Main Authors: Kwok, Ryan T. K., Shi, Haibin, Liu, Jianzhao, Xing, Bengang, Tang, Ben Zhong, Liu, Bin
• Other Authors: School of Physical and Mathematical Sciences
• Format: Article
• Language: English
• Published: 2013
• Online Access: https://hdl.handle.net/10356/97650; http://hdl.handle.net/10220/11235
• Institution: Nanyang Technological University

Real-time monitoring of cell apoptosis could provide valuable insights into early detection of therapy efficiency and evaluation of disease progression. In this work, we designed and synthesized a new live-cell-permeable, fluorescent light-up probe for real-time cell apoptosis imaging. The probe is comprised of a hydrophilic caspase-specific Asp-Glu-Val-Asp (DEVD) peptide and a hydrophobic tetraphenylethene (TPE) unit, a typical fluorogen with aggregation-induced emission characteristics. In aqueous solution, the probe is almost nonfluorescent but displays significant fluorescence enhancement in response to caspase-3/-7, which are activated in the apoptotic process and able to cleave the DEVD moieties. This fluorescence “turn-on” response is ascribed to aggregation of cleaved hydrophobic TPE residues, which restricts the intramolecular rotations of TPE phenyl rings and populates the radiative decay channels. The light-up nature of the probe allows real-time monitoring of caspase-3/-7 activities both in solutions and in living cells with a high signal-to-noise ratio. The probe provides a new opportunity to screen enzyme inhibitors and evaluate the apoptosis-associated drug efficacy.