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 similar to 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.