title: Imaging PEG-like nanoprobes in tumor, transient ischemia, and inflammatory disease models.
abstract: The iron chelator deferoxamine (DFO), approved for the treatment of iron overload, has been examined as a therapeutic in a variety of conditions which iron may exacerbate. To evaluate the potential of DFO-bearing PEG-like nanoprobes (DFO-PNs) as therapeutics, we determined their pharmacokinetics (PK) in normal mice, and imaged their accumulation in a tumor model and in models of transient brain ischemia and inflammation. DFO-PNs consist of a DFO, a Cy5.5, and PEG (5 kDa or 30 kDa) attached to Lys-Cys scaffold. Tumor uptake of a [(89)Zr]:DFO-PN(10) (30 kDa PEG, diameter 10 nm) was imaged by PET, surface fluorescence, and fluorescence microscopy. DFO-PN(10) was internalized by tumor cells (fluorescence microscopy) and by cultured cells (by FACS). [(89)Zr]:DFO-PN(4.3) (5 kDa PEG, diameter 4.3 nm) concentrated at incision generated inflammations but not at sites of transient brain ischemia. DFO-PNs are fluorescent, PK tunable forms of DFO that might be investigated as antitumor or anti-inflammatory agents.
authors.forename: Moses Q
authors.initials: MQ
authors.lastname: Wilks
authors.forename: Marc D
authors.initials: MD
authors.lastname: Normandin
authors.forename: Hushan
authors.initials: H
authors.lastname: Yuan
authors.affiliation: ⊥School of Materials Science and Engineering, Chonnam National University, Gwangju, South Korea, 500-757.
authors.forename: Hoonsung
authors.initials: H
authors.lastname: Cho
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Guo
authors.forename: Fanny
authors.initials: F
authors.lastname: Herisson
authors.forename: Cenk
authors.initials: C
authors.lastname: Ayata
authors.forename: Dustin W
authors.initials: DW
authors.lastname: Wooten
authors.forename: Georges
authors.initials: G
authors.lastname: El Fakhri
authors.forename: Lee
authors.initials: L
authors.lastname: Josephson
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000175:diagnosis*; D002232:Carbocyanines / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D003676:Deferoxamine / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D007249:Inflammation / Q000175:diagnosis*; D007502:Iron Chelating Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D049329:Nanostructures / Q000032:analysis / Q000737:chemistry; D009369:Neoplasms / Q000175:diagnosis*; D061848:Optical Imaging; D011092:Polyethylene Glycols / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D051381:Rats; D017208:Rats, Wistar
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D007502:Iron Chelating Agents; D011092:Polyethylene Glycols; D003676:Deferoxamine