Spin‐State Modulation of Iron Oxide Nanoparticles via Cobalt(III) Engineering Enables Precision MRI Contrast at Ultra‐High‐Field

Abstract The development of high‐performance magnetic resonance imaging (MRI) contrast agents remains a key challenge in precision diagnostics, particularly under ultra‐high‐field (UHF) conditions. Herein, a novel class of trivalent cobalt(III)‐engineered iron oxide (TCoEIO) nanoparticles is reported and synthesized via a scalable and reproducible thermal decomposition strategy with precisely tuned metal precursor ratios. The incorporation of Co(III) ions into the spinel lattice significantly modulates the electronic spin configuration, enhancing the longitudinal relaxivity ( r ₁ = 17 m m ⁻¹ ·s ⁻¹ ), which is ≈5 times higher than that of clinical Gd‐based contrast agents (e.g., Gd‐DTPA), while maintaining strong transverse relaxivity ( r ₂ = 134 m m ⁻¹ ·s ⁻¹ ), yielding an optimal r ₂ / r ₁ ratio of 7.9. These nanoparticles exhibit excellent colloidal stability, water dispersibility, and biocompatibility, making them suitable for in vivo applications. Quantitative analysis reveals a 45.2% increase in T ₁ signal‐to‐noise ratio and 46.1% decrease in T ₂ within 30–60 min post‐injection of nanoparticles on UHF‐MRI (7.0 T), demonstrating pronounced dual‐mode contrast and favorable pharmacokinetics. Furthermore, their surface chemistry allows for facile functionalization, enabling potential integration into multi‐modal platforms. This work highlights the potential of electronic structure engineering in nanomaterials for advanced imaging applications and paves the way for the clinical translation of contrast agents tailored for next‐generation diagnostic platforms.