Corrugated-Surface Goethite Nanoparticles with Reduced Magnetization and Increased Surface Area for Enhanced T1 MRI Contrast Effect.

Gadolinium (Gd)-based MRI contrast agents are commonly used for T1 imaging but raise safety concerns, including nephrogenic systemic fibrosis and tissue buildup. Conventional iron oxide nanoparticles (IONPs), seen as safer options, often have residual magnetization, causing T2 effects and negative contrast, complicating interpretation. These limitations highlight the need for safer, positive-contrast agents with optimized relaxivity profiles. Here, we report the development of corrugated-surface iron oxide (COSIO) nanoparticles via a two-step seed-conversion strategy involving Fe3S4 intermediates and subsequent oxidative transformation into goethite (α-FeO(OH)). Unlike traditional ultrasmall IONPs, COSIO exhibits substantially reduced magnetization and a corrugated morphology that enhances water-accessible surface area, helping proton exchange. These two effects lower transverse relaxivity (r2) and increase longitudinal relaxivity (r1), respectively, leading to favorable T1 imaging performance. In vivo studies demonstrate that COSIO outperforms a clinical Gd-based contrast agent, Magnevist, in both tumor and cerebral vascular imaging, providing prolonged contrast retention and sharp vascular delineation without nonspecific enhancement. These findings highlight the significance of nanoscale morphological control in developing effective iron-based T1 MRI contrast agents.