Anchoring Ligand-Effect on Bright Contrast-Enhancing Property of Hollow Mn<sub>3</sub>O<sub>4</sub> Nanoparticle in T<sub>1</sub>‑Weighted Magnetic Resonance Imaging

Here, we describe and conceptualize the influence of surface engineering for hollow manganese oxide nanoparticles (<b>HMONs</b>)-based contrast agents for magnetic resonance imaging (MRI). A systematic study has been conducted for enhancing the relaxivities of <b>HMONs</b> by functionalizing their surface with various capping ligands having different anchoring groups (carboxylate, alcohol, thiol, and amine). Among all studied ligands, carboxylate-anchored ligands exhibit significant increase in magnetization value upon surface capping of <b>HMON</b>. Contrary to the previous hypotheses based on the surface-Mn<sup>2+</sup> ions accessibility to water molecules, we proposed surface capping induced magnetization in <b>HMON</b> is responsible for the enhanced relaxivity (<i>r</i><sub>1</sub>) value. Further, <i>in vivo</i> imaging efficacy of oleate-capped HMON (<b>OA-HMON</b>) has been demonstrated in mouse brain. This study provides an insightful understanding of contrast enhancement and modulation by surface ligands on manganese oxide-based T<sub>1</sub>-contrast agents.