title: One-step, room-temperature synthesis of glutathione-capped iron-oxide nanoparticles and their application in in vivo T1-weighted magnetic resonance imaging.
abstract: 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(-1) s(-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.
authors.affiliation: Department of Chemistry, National Taiwan University, Taipei, 10617, Taiwan.
authors.forename: Chien-Liang
authors.initials: CL
authors.lastname: Liu
authors.forename: Yung-Kang
authors.initials: YK
authors.lastname: Peng
authors.forename: Shang-Wei
authors.initials: SW
authors.lastname: Chou
authors.forename: Wei-Hsuan
authors.initials: WH
authors.lastname: Tseng
authors.forename: Yu-Jui
authors.initials: YJ
authors.lastname: Tseng
authors.forename: Hsieh-Chih
authors.initials: HC
authors.lastname: Chen
authors.forename: Jong-Kai
authors.initials: JK
authors.lastname: Hsiao
authors.forename: Pi-Tai
authors.initials: PT
authors.lastname: Chou
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D001921:Brain / Q000378:metabolism; D003287:Contrast Media / Q000737:chemistry; D005290:Ferric Compounds / Q000737:chemistry*; D005978:Glutathione / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D007668:Kidney / Q000473:pathology; D008027:Light; D008279:Magnetic Resonance Imaging; D053768:Metal Nanoparticles / Q000737:chemistry*; D008670:Metals / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000737:chemistry; D051381:Rats; D012542:Scattering, Radiation; D013696:Temperature
chemical_list: D001672:Biocompatible Materials; D003287:Contrast Media; D005290:Ferric Compounds; D008670:Metals; D009943:Organophosphorus Compounds; C014850:tetramethylolphosphonium chloride; C000499:ferric oxide; D005978:Glutathione
keywords: bio-imaging; biomedical applications; contrast agents; glutathione; iron; nanomedicine