title: Sensitive CEST agents based on nucleic acid imino proton exchange: detection of poly(rU) and of a dendrimer-poly(rU) model for nucleic acid delivery and pharmacology.
abstract: It is shown that the exchange properties of the imino and hydroxyl protons of polyuridilic acid (poly(rU)) allow use of this compound as a chemical-exchange saturation transfer (CEST) contrast agent. A proton/proton sensitivity enhancement factor of over 5000 per imino proton allowed the detection of a few micromolar of polymer (2000 uridine units; 644 kD) with a 50% change in the water signal. The enhancement factor would increase further at even lower concentrations, opening up the submicromolar range. When poly(rU) was complexed to a dendrimer carrying 250 positive charges, the stoichiometry was approximately one RNA for 10 dendrimers. The sensitivity enhancement was reduced but remained large (2300/imino proton), bringing enhanced CEST visibility to the dendrimers. The net charge of the complex was positive, suggesting that the complexed dendrimers would still interact with cell membranes, and that the RNA-dendrimer complex could provide a model for a gene delivery system with good CEST visibility.
authors.affiliation: Johns Hopkins University School of Medicine, Department of Radiology, Baltimore, Maryland 21205, USA.
authors.forename: Karim
authors.initials: K
authors.lastname: Snoussi
authors.forename: Jeff W M
authors.initials: JW
authors.lastname: Bulte
authors.forename: Maurice
authors.initials: M
authors.lastname: Guéron
authors.forename: Peter C M
authors.initials: PC
authors.lastname: van Zijl
mesh_terms: D003287:Contrast Media / Q000737:chemistry*; D008954:Models, Biological; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011072:Poly U / Q000737:chemistry*; D011522:Protons; D014162:Transfection / Q000379:methods
chemical_list: D003287:Contrast Media; D011522:Protons; D011072:Poly U