Core–Shell–Shell NaYbF4:Tm@CaF2@NaDyF4 Nanocomposites for Upconversion/T2‑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 NaYbF4:Tm@CaF2@NaDyF4 composed of an ∼9.5 nm NaYbF4:Tm nanocrystal as the core, ∼2 nm CaF2 as the middle layer, and 1–2 nm NaDyF4 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 r2 relaxivity of 41.1 mM–1 s–1. These results confirmed that the introduction of a middle CaF2 layer was necessary as a barrier to reduce cross-relaxation and the surface quenching effect, thus enhancing the upconversion emission of Tm3+. This citrate-modified NaYbF4:Tm@CaF2@NaDyF4 nanocomposite was used as a multifunctional contrast agent for trimodal lymphatic bioimaging with T2-weighted magnetic resonance imaging (MRI), CT, and UCL imaging. The concept of fabricating a core–multishell nanostructure and the introduction of a Dy3+-based host as an outer layer is a useful strategy and can be used to develop a novel multifunctional nanoprobe for multimodality bioimaging.