title: Long-circulating perfluorooctyl bromide nanocapsules for tumor imaging by 19FMRI.
abstract: PLGA-PEG nanocapsules containing a liquid core of perfluorooctyl bromide were synthesized by an emulsion-evaporation process and designed as contrast agents for (19)F MRI. Physico-chemical properties of plain and PEGylated nanocapsules were compared. The encapsulation efficiency of PFOB, estimated by (19)F NMR spectroscopy, is enhanced when using PLGA-PEG instead of PLGA. PLGA-PEG nanocapsule diameter, measured by Dynamic Light Scattering is around 120 nm, in agreement with Transmission Electron microscopy (TEM) observations. TEM and Scanning Electron Microscopy (SEM) reveal that spherical core-shell morphology is preserved. PEGylation is further confirmed by Zeta potential measurements and X-ray Photoelectron Spectroscopy. In vitro, stealthiness of the PEGylated nanocapsules is evidenced by weak complement activation. Accumulation kinetics in the liver and the spleen was performed by (19)F MRI in mice, during the first 90 min after intravenous injection. In the liver, plain nanocapsules accumulate faster than their PEGylated counterparts. We observe PEGylated nanocapsule accumulation in CT26 xenograft tumor 7 h after administration to mice, whereas plain nanocapsules remain undetectable, using (19)F MRI. Our results validate the use of diblock copolymers for PEGylation to increase the residence time of nanocapsules in the blood stream and to reach tumors by the Enhanced Permeation and Retention (EPR) effect.
authors.affiliation: Univ Paris-Sud, UMR CNRS 8612, LabEx LERMIT, 5 rue Jean-Baptiste Clément, Châtenay-Malabry, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Diou
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tsapis
authors.forename: Céline
authors.initials: C
authors.lastname: Giraudeau
authors.forename: Julien
authors.initials: J
authors.lastname: Valette
authors.forename: Claire
authors.initials: C
authors.lastname: Gueutin
authors.forename: Fanchon
authors.initials: F
authors.lastname: Bourasset
authors.forename: Sandrine
authors.initials: S
authors.lastname: Zanna
authors.forename: Christine
authors.initials: C
authors.lastname: Vauthier
authors.forename: Elias
authors.initials: E
authors.lastname: Fattal
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology*; D003287:Contrast Media / Q000138:chemical synthesis; D005260:Female; D005466:Fluorocarbons / Q000737:chemistry; D006842:Hydrocarbons, Brominated; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size
chemical_list: D003287:Contrast Media; D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; D053769:Nanocapsules; C003072:perflubron