Direct immobilization of manganese chelates on silica nanospheres for MRI applications

The development of tissue specific magnetic resonance imaging (MRI) contrast agents (CAs) is very desirable to achieve high contrast ratio combined with excellent anatomical details. To this end, we introduce a highly effective manganese(II) containing silica material, with the aim to shorten the longitudinal (T₁) relaxation time. The microporous silica nanospheres (MSNSs) with enlarged porosity and specific surface area were prepared by a surfactant assisted aqueous method. Subsequently, the surface silanol groups were amino-functionalized, reacted with diethylenetriaminepentaacetic (DTPA) dianhydride and finally deposited with Mn²⁺. After comprehensive characterization, the MRI properties of functionalized MSNSs were investigated. The resulting nanospheres demonstrated substantial contrast enhancement during the in vitro MRI investigations, which was also evidenced by significant contrast enhancement on T₁-weighted MR images in vivo. Moreover, in vitro cytotoxicity assay of functionalized MSNSs on hepatocyte mono- and hepatocyte-Kuppfer cell co-cultures showed no significant decrease in cell viability. Our findings confirmed our hypothesis, that Mn²⁺-chelating MSNSs are appropriate candidates for liver-specific T₁-weighted MRI CAs with high relaxivities (r₁=7.18mM^-1s^-1).