Emitting/Sensitizing Ions Spatially Separated Lanthanide Nanocrystals for Visualizing Tumors Simultaneously through Up‐ and Down‐Conversion Near‐Infrared II Luminescence In Vivo

Near-infrared lights have received increasing attention regarding imaging applications owing to their large tissue penetration depth, high spatial resolution, and outstanding signal-to-noise ratio, particularly those falling in the second near-infrared window (NIR II) of biological tissues. Rare earth nanoparticles containing Er3+ ions are promising candidates to show up-conversion luminescence in the first near-infrared window (NIR I) and down-conversion luminescence in NIR II as well. However, synthesizing particles with small size and high NIR II luminescence quantum yield (QY) remains challenging. Er3+ ions are herein innovatively combined with Yb3+ ions in a NaErF4 @NaYbF4 core/shell manner instead of being codoped into NaLnF4 matrices, to maximize the concentration of Er3+ in the emitting core. After further surface coating, NaErF4 @NaYbF4 @NaYF4 core/shell/shell particles are obtained. Spectroscopy studies are carried out to show the synergistic impacts of the intermediate NaYbF4 layer and the outer NaYF4 shell. Finally, NaErF4 @NaYbF4 @NaYF4 nanoparticles of 30 nm with NIR II luminescence QY up to 18.7% at room temperature are obtained. After covalently attaching folic acid on the particle surface, tumor-specific nanoprobes are obtained for simultaneously visualizing both subcutaneous and intraperitoneal tumor xenografts in vivo. The ultrahigh QY of down-conversion emission also allows for visualization of the biodistribution of folate receptors.