Zwitterion-Coated Ultrasmall MnO Nanoparticles Enable Highly Sensitive T₁‑Weighted Contrast-Enhanced Brain Imaging

Manganese oxide nanoparticles (NPs) have attracted increasing attention recently as contrast agents (CAs) for magnetic resonance imaging (MRI). However, the clinical translation and popularization of conventional MnO NPs are hampered by their relatively poor imaging performance. Herein, we report the construction of ultrasmall MnO NPs (USMnO) via a one-pot synthetic approach that show a much better capability of T₁-weighted contrast enhancement for MRI (r₁ = 15.6 ± 0.4 mM^–1 s^–1 at 0.5 T) than MnCl₂ and conventional large-sized MnO NPs (MnO-22). These USMnO are further coated with zwitterionic dopamine sulfonate (ZDS) molecules, which improves their biocompatibility and prevents nonspecific binding of serum albumins. Interestingly, USMnO@ZDS are capable of passing through the blood–brain barrier (BBB), which enables the acquisition of clear images showing brain anatomic structures with T₁-weighted contrast-enhanced MRI. Therefore, our USMnO@ZDS could be used as a promising MRI CA for the flexible and accurate diagnosis of brain diseases, which is also instructive for the construction of manganese-based CA with a high MRI performance.