Core–Shell–Shell NaYbF<sub>4</sub>:Tm@CaF<sub>2</sub>@NaDyF<sub>4</sub> Nanocomposites for Upconversion/T<sub>2</sub>‑Weighted MRI/Computed Tomography Lymphatic Imaging

To circumvent the defects of different bioimaging techniques, the development of multifunctional probes for multimodality bioimaging is required. In the present study, a lanthanide-based core–shell–shell nanocomposite NaYbF<sub>4</sub>:Tm@CaF<sub>2</sub>@NaDyF<sub>4</sub> composed of an ∼9.5 nm NaYbF<sub>4</sub>:Tm nanocrystal as the core, ∼2 nm CaF<sub>2</sub> as the middle layer, and 1–2 nm NaDyF<sub>4</sub> as the outermost shell was designed and synthesized. Following surface modification with the ligand, citrate acid, this nanocomposite was hydrophilic, emitted intense upconversion luminescence (UCL), and displayed a high X-ray computed tomography (CT) value of ∼490 Hounsfield units (HU) and excellent <i>r</i><sub>2</sub> relaxivity of 41.1 mM<sup>–1</sup> s<sup>–1</sup>. These results confirmed that the introduction of a middle CaF<sub>2</sub> layer was necessary as a barrier to reduce cross-relaxation and the surface quenching effect, thus enhancing the upconversion emission of Tm<sup>3+</sup>. This citrate-modified NaYbF<sub>4</sub>:Tm@CaF<sub>2</sub>@NaDyF<sub>4</sub> nanocomposite was used as a multifunctional contrast agent for trimodal lymphatic bioimaging with T<sub>2</sub>-weighted magnetic resonance imaging (MRI), CT, and UCL imaging. The concept of fabricating a core–multishell nanostructure and the introduction of a Dy<sup>3+</sup>-based host as an outer layer is a useful strategy and can be used to develop a novel multifunctional nanoprobe for multimodality bioimaging.