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

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.