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.