title: Nucleophilic cross-linked, dextran coated iron oxide nanoparticles as basis for molecular imaging: synthesis, characterization, visualization and comparison with previous product.
abstract: We present a new synthesis protocol for a multivalent, multimodality, nucleophilic nanoparticle ideal for in vivo imaging. Stability requirements necessitated covalent cross-linking of the carbohydrate cage, easy functionalization the introduction of sterically accessible amine groups. The new protocol aimed at more uniform particle size, less clustering and superior magnetic properties compared with commercial nanoparticles. Particles were precipitated from Fe(2+) and Fe(3+) in the presence of 10 kDa dextran monodispersed from the aerosol phase. Cross-linking was achieved with epichlorhydrin, nuclophilication with NH3, purification with ultrafiltration and dialysis. Particles and a commercial product (Rienso®, Takeda Pharma) underwent physicochemical characterizations. Biocompatibility was assessed by Resazurin on LLC-PK1 cells; the internalization rate was measured for three cell lines (HAEC, HASMC, HT29). Core size was 5.61 ± 1.25 nm; hydrodynamic size was 49.56 ± 11.73 nm. The number of sterically accessible amine groups averaged 9.9. The cores showed cubic magnetite structure. Values of r1 and r2 were 10.9 and 148.17 mM(-1) s(-1). Cellular viability was unchanged after incubation. Introduction of aerosol phase dextran resulted in a reduction of the overall hydrodynamic diameter and a narrower size distribution of the synthesized particles. Electron tomography visualized for the first time the postulated 'hairy layer' of the dextran coating and enabled the measurement of the overall diameter of 100.2 ± 7.92 nm. The resulting nanoparticle is biocompatible, functionalizable and detectable at nanomolar concentrations with MRI and optical imaging. It can potentially serve as a platform for multimodal molecular imaging and targeted therapy approaches.
authors.affiliation: Division of Cardiovascular and Interventional Radiology, Department of Biomedical Imaging, Medical University, Vienna, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Borny
authors.forename: Thomas
authors.initials: T
authors.lastname: Lechleitner
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmiedinger
authors.forename: Martin
authors.initials: M
authors.lastname: Hermann
authors.forename: Richard
authors.initials: R
authors.lastname: Tessadri
authors.forename: Günther
authors.initials: G
authors.lastname: Redhammer
authors.forename: Josef
authors.initials: J
authors.lastname: Neumüller
authors.forename: Dontscho
authors.initials: D
authors.lastname: Kerjaschki
authors.forename: Gundula
authors.initials: G
authors.lastname: Berzaczy
authors.forename: Gürkan
authors.initials: G
authors.lastname: Erman
authors.forename: Martin
authors.initials: M
authors.lastname: Popovic
authors.forename: Johannes
authors.initials: J
authors.lastname: Lammer
authors.forename: Martin
authors.initials: M
authors.lastname: Funovics
mesh_terms: D003287:Contrast Media / Q000737:chemistry; D003911:Dextrans / Q000737:chemistry; D005290:Ferric Compounds / Q000737:chemistry; D006801:Humans; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry; D057054:Molecular Imaging; D010316:Particle Size
chemical_list: D003287:Contrast Media; D003911:Dextrans; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; C000499:ferric oxide
keywords: CLIO; MION; Rienso®; cross-linked iron oxide particles; hairy layer; multimodal molecular imaging; particle synthesis; physiochemical characterization