Activated Surface Charge‐Reversal Manganese Oxide Nanocubes with High Surface‐to‐Volume Ratio for Accurate Magnetic Resonance Tumor Imaging

Investigating the surface structure, including crystal surface and surface‐coating ligands, of nanoparticulate T₁ contrast agent may help to understand the T₁ relaxation enhancement in vitro and in vivo. This study presents a novel strategy to develop high‐performance T₁ magnetic resonance imaging (MRI) contrast agents through optimizing the nanocrystal surface and the nanobio interface. Based on the optimized crystal surface, the novel manganese oxide nanocubes (MOCs) show significantly higher surface‐to‐volume ratio and an approximately threefold higher r₁ value compared to traditional manganese oxide nanospheres. Concurrently, transferring MOCs into aqueous media by dopamine derivatization can avoid the oxidation of Mn(II) ions and provide abundant magnetic core. This optimized surface endows MOCs with a high chemical exchange efficiency during T₁ relaxation. Of particular significance, a rationally designed pH‐induced charge‐switchable surfaces can be negatively charged and corona‐free in blood and positively charged surface in tumor sites. This unique feature improves the circulation behavior of this intelligent T₁ contrast agent in blood and increases cancer cell uptake to achieve accurate detection of solid tumor, holding great potential in aiding early and precise tumor diagnosis. This study provides a novel tool for sophisticated design of high‐performance T₁ MRI contrast agents in bioimaging applications.