Self-assembly of Gd3+-bound keplerate polyanions into nanoparticles as a route for the synthesis of positive MRI contrast agents. Impact of the structure on the magnetic relaxivity

Abstract

The present work introduces Gd³⁺ complexes with giant keplerate polyanions as a promising basis for MRI contrast agents. The impact of Gd³⁺ binding with different building blocks of keplerates on the magnetic relaxivity of the complexes is revealed by comparative study of the keplerates [{Mo₆O₂₁}₁₂{Mo₂O₄(OAc)}₃₀]⁴²⁻, [{Mo₆O₂₁}₁₂{Mo₂O₄(HPO₄)}₃₀]⁷²⁻, and [{Mo₆O₂₁}₁₂{Mo₂O₂S₂(OAc)}₃₀]⁴²⁻. Unprecedentedly high longitudinal and transverse relaxivity values (up to 250 and 300 mM⁻¹ s⁻¹ correspondingly) are achieved for the keplerates possessing edl{Mo₂O₄(OAc)} and {Mo₂O₄(HPO₄²⁻)} moieties under their 1 : 1 complex formation with Gd³⁺. The transformation of the external pores from Mo₉O₉ to Mo₉O₆S₃ in the {Mo₂O₂S₂(OAc)}-keplerate and an increase in the Gd³⁺-to-keplerate ratio are the factors that decrease the relaxivity. The rapid degradation of the free keplerates in aqueous solutions restricts the use of the Gd³⁺-bound keplerates with 1 : 1 stoichiometry as MRI contrast agents. In this work, the optimized stoichiometry of the complexes, their self-assembly into ultra-small nanoparticles and their hydrophilic coating by a triblock copolymer are highlighted as tools for increasing both the colloid and chemical stability of the keplerate complexes. Optimal keplerate compositions have been identified to achieve a compromise of low cytotoxicity and high stability; these Gd³⁺-bound keplerates exhibit longitudinal and transverse relaxivity values (95 and 114 mM⁻¹ s⁻¹, respectively), well within the region of interest for MRI techniques.