title: Individually Stabilized, Superparamagnetic Nanoparticles with Controlled Shell and Size Leading to Exceptional Stealth Properties and High Relaxivities.
abstract: Superparamagnetic iron oxide nanoparticles (SPION) have received immense interest for biomedical applications, with the first clinical application as negative contrast agent in magnetic resonance imaging (MRI). However, the first generation MRI contrast agents with dextran-enwrapped, polydisperse iron oxide nanoparticle clusters are limited to imaging of the liver and spleen; this is related to their poor colloidal stability in biological media and inability to evade clearance by the reticuloendothelial system. We investigate the qualitatively different performance of a new generation of individually PEG-grafted core-shell SPION in terms of relaxivity and cell uptake and compare them to benchmark iron oxide contrast agents. These PEG-grafted SPION uniquely enable relaxivity measurements in aqueous suspension without aggregation even at 9.4 T magnetic fields due to their extraordinary colloidal stability. This allows for determination of the size-dependent scaling of relaxivity, which is shown to follow a d2dependence for identical core-shell structures. The here introduced core-shell SPION with ∼15 nm core diameter yield a higher R2relaxivity than previous clinically used contrast agents as well as previous generations of individually stabilized SPION. The colloidal stability extends to control over evasion of macrophage clearance and stimulated uptake by SPION functionalized with protein ligands, which is a key requirement for targeted MRI.
authors.affiliation: Department of Nanobiotechnology, Institute for Biologically Inspired Materials, University of Natural Resources and Life Sciences , Muthgasse 11, 1190 Vienna, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lassenberger
authors.affiliation: Department of Nanobiotechnology, Institute for Biologically Inspired Materials, University of Natural Resources and Life Sciences , Muthgasse 11, 1190 Vienna, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Scheberl
authors.affiliation: Department of Biomedical Imaging and Image-guided Therapy, Division of Molecular and Gender Imaging, Medical University Vienna , Waehringer Guertel 18-20, 1090 Vienna, Austria.|Department of Neurosurgery, University of Erlangen-Nürnberg , Schwabachanlage 6, 91054 Erlangen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Stadlbauer
authors.affiliation: Department of Biomedical Imaging and Image-guided Therapy, Division of Molecular and Gender Imaging, Medical University Vienna , Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Stiglbauer
authors.affiliation: Department of Biomedical Imaging and Image-guided Therapy, Division of Molecular and Gender Imaging, Medical University Vienna , Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Helbich
authors.affiliation: Department of Nanobiotechnology, Institute for Biologically Inspired Materials, University of Natural Resources and Life Sciences , Muthgasse 11, 1190 Vienna, Austria.
authors.forename: Erik
authors.identifier: http://orcid.org/0000-0003-1417-5576
authors.initials: E
authors.lastname: Reimhult
mesh_terms: D003287:Contrast Media; D003911:Dextrans; D005290:Ferric Compounds; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles
chemical_list: D003287:Contrast Media; D003911:Dextrans; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles
keywords: core−shell; macrophage nanoparticle uptake; size-dependent relaxivity; superparamagnetic iron oxide nanoparticles; targeted magnetic resonance imaging