Mn(II)-Conjugated silica nanoparticles as potential MRI probes

Novel Mn(II)-based nanoprobes were rationally designed as high contrast enhancing agents for magnetic resonance imaging (MRI) and obtained by anchoring a Mn(II)-CDTA derivative to the surface of organo-modified silica nanoparticles (SiNPs). Large payloads of paramagnetic metal-chelates have been immobilized on biocompatible SiNPs with spherical shape and narrow size distribution of 80-90 nm, resulting in a relaxivity gain of 250% at clinical fields (0.5 T) as compared to the free chelate. Such substantial efficacy enhancement of the nanoprobes is mainly attributed to the restriction of the rotational dynamics of the conjugated complex, as revealed by comprehensive ¹H-NMR relaxometric investigations. The paramagnetic nanospheres exhibit good colloidal stability over time in biological matrices, allowing for MRI applications. High image contrast was found in T_1w-MRI images collected at 1 T on phantoms containing relatively small amounts of contrast agent (CA), for which low cellular toxicity was observed on three different cell lines. Preliminary in vivo studies on healthy mice demonstrated the efficiency of the novel Mn-based silica nanoparticle as T_1w-MRI probes, resulting in significant contrast enhancement in the liver. These findings demonstrate that these novel Mn-SiNPs are high efficacy CAs suitable for preclinical MRI applications.