Ultrasmall Hydrophilic Gd‐Free Contrast Agents via Ligand Directed Hydrolysis for Efficient Magnetic Resonance Imaging

Abstract A Mn‐anchored ultrasmall hydrophilic TiO 2 based contrast agent (TMn‐PMM) is prepared via ligand directed hydrolysis with high relaxivity (71.4 mM −1 s −1 under 0.5 T, which is 16.7 times higher than that of commercial Gd‐contrast agents). Results indicate that the presences of ligands (oleylamine/oleic acid) tend to obtain ultrasmall TiO 2 with higher degree of crystallinity even after ligand removal by etching, which lead to less surface oxygen vacancy than that obtained with ethanol. The well‐dispersed Mn sites and rich hydroxyl groups (O─H) in TMn‐PMM significantly increase the effective active sites for interaction with surrounding water protons, in addition to extending rotational correlation time ( τ R ), thus, affording TMn‐PMM with satisfied magnetic resonance imaging (MRI) performance in vivo. Moreover, the ultrasmall size and zwitterionic polymer coating of TMn‐PMM ensure excellent biocompatibility with desirable body clearance.