Europium-Doped Nanoparticles for Cellular Luminescence Lifetime Imaging via Multiple Manipulations of Aggregation...

Luminescence lifetime imaging (LLIM) holds great promise in biomedical research owing to its excellent sensitivity and remarkable temporal-spatial resolution, but the development of effective long-lived luminescent probes for LLIM remains an unmet need. Herein, we designed two water-dispersible europium-doped nanoparticles (Eu-D1 and Eu-D2 NPs) for cellular LLIM, showing intense red luminescence emission and an increased lifetime of 4 orders of magnitude (∼56 000 times) than undoped NPs, which could be attributed to the multiple manipulations of their aggregation states, including efficient Förster resonance energy transfer (FRET), suppressed self-quenching, and restrained solvent effects. With good bioavailability, the as-developed NPs were demonstrated as reliable candidates for long-lifetime imaging agents. Such a simple and versatile strategy could be extended to develop various luminescent nanoprobes for advanced high-precision bioimaging.