Nucleophilic cross‐linked, dextran coated iron oxide nanoparticles as basis for molecular imaging: synthesis, characterization, visualization and comparison with previous product. (22nd April 2014)

• Record Type: Journal Article
• Authors: Borny, Robert; Lechleitner, Thomas; Schmiedinger, Thomas; Hermann, Martin; Tessadri, Richard; Redhammer, Günther; Neumüller, Josef; Kerjaschki, Dontscho; Berzaczy, Gundula; Erman, Gürkan; Popovic, Martin; Lammer, Johannes; Funovics, Martin
• Is Part Of: Contrast media & molecular imaging. Volume 10:Number 1(2015:Jan./Feb.)
• Page Start: 18
• Page End: 27
• Publication Date: 2014-04-22
• Subjects: Diagnostic imaging -- Periodicals; Magnetic resonance imaging -- Periodicals; Contrast media (Diagnostic imaging) -- Periodicals; Contrast Media -- Periodicals; Diagnostic Imaging -- Periodicals; Substances de contraste -- Périodiques; Diagnostics moléculaires -- Périodiques; Imagerie médicale; Substance de contraste; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.0754
• DOI: 10.1002/cmmi.1595
• Languages: English
• ISSNs: 1555-4309

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>We present a new synthesis protocol for a multivalent, multimodality, nucleophilic nanoparticle ideal for <italic>in vivo</italic> 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<sup>2+</sup> and Fe<sup>3+</sup> in the presence of 10 kDa dextran monodispersed from the aerosol phase. Cross‐linking was achieved with epichlorhydrin, nuclophilication with NH<sub>3</sub>, 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 <italic>r</italic><sub>1</sub> and <italic>r</italic><sub>2</sub> were 10.9 and 148.17 m<sc>m</sc><sup>−1</sup> s<sup>−1</sup>. 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. Copyright © 2014 John Wiley & Sons, Ltd.</p> </abstract>