The development of T1/T2 dual-modality contrast agents in magnetic resonance imaging (MRI) is beneficial for achieving accurate imaging and eliminating artifacts. However, T1 and T2 agents in the case of direct contact will interfere with each other, and the intrinsic mechanism remains unclear yet.
      To disclose the underlying mechanism governing the relaxometric properties of T1/T2 dual-modality contrast agents, herein NaDyF₄@NaREF₄@NaGdF₄:Yb,Er (RE =Gd, Er, Y) core-shell-shell structured nanoparticles were designed to integrate T1 signal units (Gd³⁺) and T2 signal units (Dy³⁺) in a single nanocrystal and systematically investigated the interaction between T1 and T2 agents by varying the NaREF₄ spacer layer. Careful relaxometric studies in combination with theoretical analysis reveal that strong coupling interaction between the electron clouds of Dy³⁺ and Gd³⁺ decreases the r1 value of the core-shell-shell nanoparticles. But this interaction can be manipulated by the spacer layer NaREF₄ containing RE element with weak distortion ability of electron cloud such as Y³⁺ to effectively suppress the negative impact of Dy³⁺. The mechanism was supported by upconversion luminescence studies, that is, when NaYF₄ is involved to separate Dy³⁺ in the core and RE³⁺ in the outer shell, the upconversion luminescence is sufficiently enhanced, which supports that the NaYF₄ spacer layer can efficiently reduce the interactions between Dy³⁺ and Gd³⁺ for achieving high performance magnetic/upconversion particles for T1/T2 MR and optical imaging applications. In addition, a thicker NaYF₄ spacer layer is also found to be favorable for achieving higher r1 value.
      Although the negative impact of Dy³⁺ on both r1 and upconversion luminescence efficiency are not completely ruled out with NaYF₄ spacer layer, the current study offers a reliable understanding for tailoring the relaxometric properties and upconversion luminescent properties of RE nanoparticles that are potentially useful for biomedical imaging applications.

                                                                                                                                                                                                         Jiayi Huang et al.