One-Step, Room-Temperature Synthesis of Glutathione-Capped Iron-Oxide Nanoparticles and their Application in In Vivo T₁-Weighted Magnetic Resonance Imaging

The room-temperature, aqueous-phase synthesis of iron-oxide nanoparticles (IO NPs) with glutathione (GSH) is reported. The simple, one-step reduction involves GSH as a capping agent and tetrakis(hydroxymethyl)phosphonium chloride (THPC) as the reducing agent; GSH is an anti-oxidant that is abundant in the human body while THPC is commonly used in the synthesis of noble-metal clusters. Due to their low magnetization and good water-dispersibility, the resulting GSH-IO NPs, which are 3.72 ± 0.12 nm in diameter, exhibit a low r₂ relaxivity (8.28 mm^-1s^-1) and r₂/r₁ ratio (2.28) - both of which are critical for T₁ contrast agents. This, together with the excellent biocompatibility, makes these NPs an ideal candidate to be a T₁ contrast agent. Its capability in cellular imaging is illustrated by the high signal intensity in the T₁-weighted magnetic resonance imaging (MRI) of treated HeLa cells. Surprisingly, the GSH-IO NPs escape ingestion by the hepatic reticuloendothelial system, enabling strong vascular enhancement at the internal carotid artery and superior sagittal sinus, where detection of the thrombus is critical for diagnosing a stroke. Moreover, serial T₁- and T₂-weighted time-dependent MR images are resolved for a rat's kidneys, unveiling detailed cortical-medullary anatomy and renal physiological functions. The newly developed GSH-IO NPs thus open a new dimension in efforts towards high-performance, long-circulating MRI contrast agents that have biotargeting potential. An unprecedented room-temperature, aqueous-phase synthesis of iron-oxide nanoparticles (IO NPs) capped with glutathione (GSH) is reported. The GSH-IO NPs can improve the signal intensity in T₁-weighted magnetic resonance imaging (MRI). The NPs avoid ingestion by the reticuloendothelial system, and they successfully reveal the detailed anatomy and physiological functions in animal models. As a result, these NPs provide a new route towards high-performance, long-circulating MRI contrast agents with bio-targeting potential.