A novel “AND” logic platform based on ICT and FRET for constructing near-infrared dual-locked fluorescence probe

In this study, a new “AND” logic platform based on intramolecular charge transfer (ICT) and Förster resonance energy transfer (FRET) is developed for constructing a near-infrared dual-locked fluorescence probe with high resistance to pH in biological environments. Using esterase and glutathione (GSH) as representative activators, the developed dual-locked probe BBQ650-SS-ClHC-E discriminates cancer cells from normal cells. The esterase substrate in the probe blocks the ICT process, while the GSH substrate acts as a linker to connect the fluorescence part with the quencher part to induce the FRET process. The fluorescence activation at 732 nm operates as an “AND” logic that depends on the “ICT-on” and “FRET-off” states in the presence of both esterase and GSH. BBQ650-SS-ClHC-E can successfully discriminate HeLa, 4T1, and RAW264.7 cancer cells from HFL1 normal cells and 4T1 tumor-bearing cells in living mice. This new platform can be used to develop dual-locked fluorescence probes.