In Vivo NIR-II Fluorescence Lifetime Imaging of Whole-Body Vascular Using High Quantum Yield Lanthanide-Doped Nanoparticles

Second near infrared (NIR-II, 1000-1700 nm) fluorescence lifetime imaging is a powerful tool for biosensing, anti-counterfeiting, and multiplex imaging. However, the low photoluminescence quantum yield (PLQY) of fluorescence probes in NIR-II region limits its data collecting efficiency and accuracy, especially in multiplex molecular imaging in vivo. To solve this problem, lanthanide-doped nanoparticles (NPs) beta-NaErF4: 2%Ce@NaYbF4@NaYF4 with high PLQY and tunable PL lifetime through multi-ion doping and core-shell structural design, are presented. The obtained internal PLQY can reach up to 50.1% in cyclohexane and 9.2% in water under excitation at 980 nm. Inspired by the above results, a fast NIR-II fluorescence lifetime imaging of whole-body vascular in mice is successfully performed by using the homebuilt fluorescence lifetime imaging system, which reveals a murine abdominal capillary network with low background. A further demonstration of fluorescence lifetime multiplex imaging is carried out in molecular imaging of atherosclerosis cells and different organs in vivo through NPs conjugating with specific peptides and different injection modalities, respectively. These results demonstrate that the high PLQY NPs combined with the homebuilt fluorescence lifetime imaging system can realize a fast and high signal-to-noise fluorescence lifetime imaging; thus, opening a road for multiplex molecular imaging of atherosclerosis.

Automated summary

Second near infrared (NIR-II) fluorescence lifetime imaging in the range of 1000-1700 nm has versatile applications in biosensing, anti-counterfeiting, and multiplex imaging. However, the low photoluminescence quantum yield (PLQY) of fluorescence probes hinders its data collecting efficiency, especially in vivo multiplex molecular imaging. To address this issue, lanthanide-doped nanoparticles with high PLQY and tunable PL lifetime were developed. By utilizing these nanoparticles in a homebuilt fluorescence lifetime imaging system, fast and high signal-to-noise fluorescence lifetime imaging was achieved, enabling multiplex molecular imaging of atherosclerosis.