High-stability spherical lanthanide nanoclusters for magnetic resonance imaging

High-nuclear lanthanide clusters have shown great potential for the administration of high-dose mononuclear gadolinium chelates in magnetic resonance imaging (MRI). The development of high-nuclear lanthanide clusters with excellent solubility and high stability in water or solution has been challenging and is very important for expanding the performance of MRI. We used N-methylbenzimidazole-2-methanol (HL) and LnCl₃·6H₂O to synthesize two spherical lanthanide clusters, Ln₃₂ (Ln = Ho, Ho₃₂; and Ln = Gd, Gd₃₂), which are highly stable in solution. The 24 ligands L^- are all distributed on the periphery of Ln₃₂ and tightly wrap the cluster core, ensuring that the cluster is stable. Notably, Ho₃₂ can remain highly stable when bombarded with different ion source energies in HRESI-MS or immersed in an aqueous solution of different pH values for 24 h. The possible formation mechanism of Ho₃₂ was proposed to be Ho(III), (L)^- and H₂O → Ho₃(L)₃/Ho₃(L)₄ → Ho₄(L)₄/Ho₄(L)₅ → Ho₆(L)₆/Ho₆(L)₇ → Ho₁₆(L)₁₉ → Ho₂₈(L)₁₅ → Ho₃₂(L)₂₄/Ho₃₂(L)₂₁/Ho₃₂(L)₂₃. To the best of our knowledge, this is the first study of the assembly mechanism of spherical high-nuclear lanthanide clusters. Spherical cluster Gd₃₂, a form of highly aggregated Gd(III), exhibits a high longitudinal relaxation rate (1 T, r₁ = 265.87 mM^-1·s^-1). More notably, compared with the clinically used commercial material Gd-DTPA, Gd₃₂ has a clearer and higher-contrast T₁-weighted MRI effect in mice bearing 4T1 tumors. This is the first time that high-nuclear lanthanide clusters with high water stability have been utilized for MRI. High-nuclear Gd clusters containing highly aggregated Gd(III) at the molecular level have higher imaging contrast than traditional Gd chelates; thus, using large doses of traditional gadolinium contrast agents can be avoided.