Breaking Through the Signal-to-Background Limit of Upconversion Nanoprobes Using a Target-Modulated Sensitizing Switch

Although lanthanide-doped upconversion nanoparticles (UCNPs) have shown great promise in biosensing and bioimaging owing to their excellent photophysical properties, researchers are facing a bottleneck of upconversion (UC) probes which is the limited signal-to-background ratio (SBR). Since UC nanoprobes are basically constructed with a luminescence resonance energy transfer (LRET) process to provide “off–on” signals, the SBR level is principally decided by the luminescence quenching efficiency which is very difficult to further improve through existing approaches. Herein, we put forward a new strategy for fabricating UC nanoprobes using an organic dye as target-modulated sensitizing switch. The dye functions as both the recognition unit for target and a potential sensitizer for upconversion luminescence (UCL). The reaction of the dye with target modulates its photophysical properties, which switches on the sensitization and affords a significantly improved SBR. The idea is validated with a proof-of-concept UC nanoprobe for glutathione (GSH) detection with the SBR of ∼30 (versus a SBR of less than 10 for most current UC nanoprobes). This probe showed good performance in GSH sensing both in vitro and in vivo. Our results indicate that the target-modulated sensitization is a useful new strategy to build UC nanoprobes. And we can reasonably expect that the breakthrough of SBR limit will make UC nanoprobe a more powerful tool in future studies