A cysteine/lipid droplets sequentially activated dual-locked fluorescent probe for accurate bioimaging of tumor tissues

The previous activatable probe toward one analyte can still produce imprecise signal as a result of the challenge cased by accurate identification in complex biological environment. As smarter molecules, dual-locked probes are able to respond to two different analyte with one or more output signals, which display significantly reduced background interference and increased spatial resolution. In this study, a smart cysteine/lipid droplets sequence-activated dual-locked fluorescent probe CN–NO2 has been designed and synthesized for the detection of tumor tissues. The recognition group of CN–NO2 removed after reacting with cysteine (Cys) and undergoing intramolecular rearrangement to generate complete fluorophores. This structure had a strong solvent effect; it could recognize lipid droplets (LDs) in cells, thus exhibiting fluorescence without secondary molecular adjustment. The fluorescence of CN–NO2 was enhanced 1752-fold after double unlocking. Importantly, the unlocking process only takes 10 min. Furthermore, the fluorescence of CN–NO2 was amplified remarkable and anchored at LDs after reacting with Cys in A549 cells. Therefore, CN–NO2 clearly indicated the site of mouse xenograft tumor in vivo. Such sequence-activated dual-locked fluorescent probes are envisioned to execute more analysis and diagnostic tasks giving these unique characteristics.