pH‐Responsive Ultrasmall Iron Oxide Nanoassemblies for Activatable T 2 / T 1 Magnetic Resonance Imaging

Magnetic resonance (MR) imaging is a widely used noninvasive diagnostic technique, in which contrast‐enhanced imaging accounts for nearly half of all clinical MRI examinations. Although gadolinium‐based contrast agents are extensively employed, their potential safety concerns have motivated the development of alternative T 1 contrast agents. Ultrasmall iron oxide nanoparticles (USIONs, ≤5 nm) have emerged as promising candidates owing to their spin‐canting effects and high surface‐to‐volume ratio; however, their short circulation time and “always‐on” MR signals result in limited target‐to‐background contrast. Herein, we report a facile pH‐responsive smart nanoassembly for switchable T 2 / T 1 ‐weighted MR imaging. The resulting USIONs/polymer nanoassemblies encapsulate multiple USIONs within a condensed hydrophobic core, leading to enhanced magnetic coupling and dominant T 2 ‐weighted MR contrast under physiological conditions. Upon exposure to acidic conditions, the nanoassemblies undergo pH‐triggered disassembly, releasing monodispersed USIONs and concomitantly activating T 1 ‐weighted MR contrast, as evidenced by a pronounced decrease in the transversal relaxivity/longitudinal relaxivity ( r 2 / r 1 ) ratio from 210 to 66. This work presents a simple and versatile strategy for constructing pH‐responsive organic/inorganic nanoassemblies and provides an in vitro proof‐of‐concept platform for activatable MR imaging.