title: Redox-triggered self-assembly of gadolinium-based MRI probes for sensing reducing environment.
abstract: Controlled self-assembly of small molecule gadolinium (Gd) complexes into nanoparticles (GdNPs) is emerging as an effective approach to design activatable magnetic resonance imaging (MRI) probes and amplify the r₁ relaxivity. Herein, we employ a reduction-controlled macrocyclization reaction and self-assembly to develop a redox activated Gd-based MRI probe for sensing a reducing environment. Upon disulfide reduction at physiological conditions, an acyclic contrast agent 1 containing dual Gd-chelates undergoes intramolecular macrocyclization to form rigid and hydrophobic macrocycles, which subsequently self-assemble into GdNPs, resulting in a ∼60% increase in r₁ relaxivity at 0.5 T. Probe 1 has high r₁ relaxivity (up to 34.2 mM(-1) s(-1) per molecule at 0.5 T) upon activation, and also shows a high sensitivity and specificity for MR detection of thiol-containing biomolecules.
authors.affiliation: Molecular Imaging Program, Departments of Radiology and Chemistry, and ‡Department of Materials Science and Engineering, Stanford University , Stanford, California 94305, United States.
authors.forename: Deju
authors.initials: D
authors.lastname: Ye
authors.forename: Prachi
authors.initials: P
authors.lastname: Pandit
authors.forename: Paul
authors.initials: P
authors.lastname: Kempen
authors.forename: Jianguo
authors.initials: J
authors.lastname: Lin
authors.forename: Liqin
authors.initials: L
authors.lastname: Xiong
authors.forename: Robert
authors.initials: R
authors.lastname: Sinclair
authors.forename: Brian
authors.initials: B
authors.lastname: Rutt
authors.forename: Jianghong
authors.initials: J
authors.lastname: Rao
mesh_terms: D005682:Gadolinium / Q000737:chemistry*; D005978:Glutathione / Q000378:metabolism; D006367:HeLa Cells; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D053768:Metal Nanoparticles / Q000737:chemistry; D010084:Oxidation-Reduction
chemical_list: D006573:Heterocyclic Compounds, 1-Ring; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D005682:Gadolinium; D005978:Glutathione