In Vivo High-Contrast Biomedical Imaging in the Second Near-Infrared Window Using Ultrabright Rare-Earth Nanoparticles.

Intravital luminescence imaging in the second near-infrared window (NIR-II) enables noninvasive deep-tissue imaging with high spatiotemporal resolution of live mammals because of the properties of suppressed light scattering and diminished autofluorescence in the long-wavelength region. Herein, we present the synthesis of a downconversion luminescence rare-earth nanocrystal with a core-shell-shell structure (NaYF@NaYbF:Er,Ce@NaYF:Ca). The structure efficiently maximized the doping concentration of the sensitizers and increased Er luminescence while preventing cross relaxation. Furthermore, Ce doping in the middle layer efficiently limited the upconversion pathway and increased downconversion by 24-fold to produce bright 1550 nm luminescence under 975 nm excitation. Finally, optimizing the inert shell coating of NaYF:Ca and liposome encapsulation reduced the luminescence quenching impact by water and improved biological metabolism. Thus, our synthesized biocompatible, ultrabright NIR-II probes provide high contrast and resolution for through-scalp and through-skull luminescence imaging of mice cerebral vasculature without craniotomy as well as imaging of mouse hindlimb microvessels.