10.1021/acsami.6b02856.s001 Ying Li Ying Li Yuyang Gu Yuyang Gu Wei Yuan Wei Yuan Tianye Cao Tianye Cao Kai Li Kai Li Shiping Yang Shiping Yang Zhiguo Zhou Zhiguo Zhou Fuyou Li Fuyou Li 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 American Chemical Society 2016 NaYbF r 2 relaxivity surface quenching effect trimodal lymphatic bioimaging upconversion MRI multifunctional contrast agent core HU NaDyF 4 Nanocomposites middle CaF 2 layer NaDyF 4 nanocomposite novel multifunctional nanoprobe introduction CT Tm nm UCL multimodality bioimaging 2016-07-01 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/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/3497663 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.