PEG-copolymer-coated iron oxide nanoparticles that avoid the reticuloendothelial system and act as kidney MRI contrast agents

Abstract

In vitro experiments have shown the great potential of magnetic nanocarriers for multimodal imaging diagnosis and non-invasive therapies. However, their extensive clinical application is still jeopardized by a fast retention in the reticuloendothelial system (RES). The other issue that restrains their potential performance is slow degradation and excretion, which increases their risks of toxicity. We report a promising case in which multicore iron oxide nanoparticles coated with a poly(4-vinylpyridine) polyethylene glycol copolymer show low RES retention and high urinary excretion, as confirmed by single photon emission computerized tomography (SPECT), gamma counting, magnetic resonance imaging (MRI) and electron microscopy (EM) biodistribution studies. These iron oxide-copolymer nanoparticles have a high PEG density in their coating which may be responsible for this effect. Moreover, they show a clear negative contrast in the MR imaging of the kidneys. These nanoparticles with an average hydrodynamic diameter of approximately 20 nm were nevertheless able to cross the glomerulus wall which has an effective pore size of approximately 6 nm. A transmission electron microscopy inspection of kidney tissue revealed the presence of iron containing nanoparticle clusters in proximal tubule cells. This therefore makes them exceptionally useful as magnetic nanocarriers and as new MRI contrast agents for the kidneys.