Non-immunogenic Dextran-Coated Superparamagnetic Iron Oxide Nanoparticles: A Biocompatible, Size-Tunable Contrast Agent for Magnetic Resonance Imaging

Int J Nanomedicine. 2017 Jul 24;12:5223-5238. doi: 10.2147/IJN.S138108. eCollection 2017.

Abstract

Iron oxide-based contrast agents have been in clinical use for magnetic resonance imaging (MRI) of lymph nodes, liver, intestines, and the cardiovascular system. Superparamagnetic iron oxide nanoparticles (SPIONs) have high potential as a contrast agent for MRI, but no intravenous iron oxide-containing agents are currently approved for clinical imaging. The aim of our work was to analyze the hemocompatibility and immuno-safety of a new type of dextran-coated SPIONs (SPIONdex) and to characterize these nanoparticles with ultra-high-field MRI. Key parameters related to nanoparticle hemocompatibility and immuno-safety were investigated in vitro and ex vivo. To address concerns associated with hypersensitivity reactions to injectable nanoparticulate agents, we analyzed complement activation-related pseudoallergy (CARPA) upon intravenous administration of SPIONdex in a pig model. Furthermore, the size-tunability of SPIONdex and the effects of size reduction on their biocompatibility were investigated. In vitro, SPIONdex did not induce hemolysis, complement or platelet activation, plasma coagulation, or leukocyte procoagulant activity, and had no relevant effect on endothelial cell viability or endothelial-monocytic cell interactions. Furthermore, SPIONdex did not induce CARPA even upon intravenous administration of 5 mg Fe/kg in pigs. Upon SPIONdex administration in mice, decreased liver signal intensity was observed after 15 minutes and was still detectable 24 h later. In addition, by changing synthesis parameters, a reduction in particle size <30 nm was achieved, without affecting their hemo- and biocompatibility. Our findings suggest that due to their excellent biocompatibility, safety upon intravenous administration and size-tunability, SPIONdex particles may represent a suitable candidate for a new-generation MRI contrast agent.

Keywords: MRI; SPION uptake; hemocompatibility; hypersensitivity reaction; superparamagnetic iron oxide nanoparticles.

MeSH terms

  • Administration, Intravenous
  • Animals
  • Biocompatible Materials / chemistry
  • Cell Survival / drug effects
  • Complement Activation / drug effects*
  • Contrast Media / administration & dosage*
  • Contrast Media / adverse effects
  • Contrast Media / chemistry*
  • Dextrans / chemistry
  • Drug Hypersensitivity / etiology
  • Ferric Compounds / chemistry
  • Humans
  • Liver / drug effects
  • Magnetic Resonance Imaging / methods
  • Magnetite Nanoparticles / administration & dosage
  • Magnetite Nanoparticles / adverse effects
  • Magnetite Nanoparticles / chemistry*
  • Mice
  • Monocytes / drug effects
  • Particle Size
  • Rabbits
  • Swine

Substances

  • Biocompatible Materials
  • Contrast Media
  • Dextrans
  • Ferric Compounds
  • Magnetite Nanoparticles
  • ferric oxide