Exploring the influence of internal surface modification of paramagnetic mesoporous silica nanoparticles on MRI relaxation dynamics

Paramagnetic mesoporous silica nanoparticles (MSNs) containing immobilised Gd3+-macrocycles are widely investigated as platforms for enhancing magnetic resonance imaging (MRI) contrast, yet the influence of the local chemical surface environment on relaxation dynamics remains underexplored. In this work, we systematically examine how internal surface functionalisation modulates the relaxometric behaviour of Gd3+-chelate modified MSNs. Monodisperse MSNs were prepared with constant Gd3+ loading and varying either proximal thiol or phenyl groups. Thiol-functionalised particles exhibited a clear enhancement in relaxivity with high thiol grafting densities. Fast field-cycling NMR fitting parameters indicated that thiols progressively restrict local rotational dynamics, likely due to changes in local viscosity inside pores coupled with changes in the hydration layer structure around the Gd3+-chelate, reaching a plateau once the grafting density exceeds the density of Gd3+-chelates. In contrast, phenyl groups produce relaxivity enhancement through steric restrictions and hydrophobic crowding that limit chelate motion. Variable-temperature studies confirm that relaxation is dominated by local rotational dynamics rather than water exchange in both cases. These findings demonstrate that different surface modifiers enhance MRI performance via distinct mechanisms, highlighting internal surface chemistry as a key consideration in the design of nanoparticulate contrast agents.