Preparation of Robust Metal-Free Magnetic Nanoemulsions Encapsulating Low-Molecular-Weight Nitroxide Radicals and Hydrophobic Drugs Directed Toward MRI-Visible Targeted Delivery

Chemistry. 2017 Nov 7;23(62):15713-15720. doi: 10.1002/chem.201702785. Epub 2017 Oct 12.

Abstract

With a view to developing a theranostic nanomedicine for targeted drug delivery systems visible by magnetic resonance (MR) imaging, robust metal-free magnetic nanoemulsions (mean particle size less than 20 nm) consisting of a biocompatible surfactant and hydrophobic, low molecular weight 2,2,5-trimethyl-5-(4-alkoxy)phenylpyrrolidine-N-oxyl radicals were prepared in pH 7.4 phosphate-buffered saline (PBS). The structure of the nanoemulsions was characterized by electron paramagnetic resonance spectroscopy, and dynamic light scattering and small-angle neutron-scattering measurements. The nanoemulsions showed high colloidal stability, low cytotoxicity, enough reduction resistance to excess ascorbic acid, and sufficient contrast enhancement in the proton longitudinal relaxation time (T1 ) weighted MR images in PBS in vitro (and preliminarily in vivo). Furthermore, the hydrophobic anticancer drug paclitaxel could be encapsulated inside the nanoparticles, and the resulting paclitaxel-loaded nanoemulsions were efficiently incorporated into HeLa cells to suppress cell growth.

Keywords: EPR spectroscopy; drug delivery; imaging agents; magnetic nanoparticles; radicals.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry*
  • Antineoplastic Agents, Phytogenic / toxicity
  • Ascorbic Acid / chemistry
  • Brain / diagnostic imaging
  • Cell Proliferation / drug effects
  • Drug Carriers / chemistry*
  • Dynamic Light Scattering
  • Electron Spin Resonance Spectroscopy
  • HeLa Cells
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Magnetic Resonance Imaging
  • Magnetite Nanoparticles / chemistry*
  • Mice
  • Molecular Weight
  • Neutron Diffraction
  • Nitrogen Oxides / chemistry*
  • Oxidation-Reduction
  • Paclitaxel / chemistry*
  • Paclitaxel / toxicity
  • Particle Size
  • Scattering, Small Angle

Substances

  • Antineoplastic Agents, Phytogenic
  • Drug Carriers
  • Magnetite Nanoparticles
  • Nitrogen Oxides
  • nitroxyl
  • Paclitaxel
  • Ascorbic Acid