Polyethylene glycol-based biocompatible and highly stable superparamagnetic iron oxide nanoclusters for magnetic resonance imaging

We developed a simple emulsion and solvent-evaporation approach for the clustering of iron oxide nanoparticles using a polyethylene glycol (PEG)-based nonionic surfactant, D-alpha-tocopheryl poly(ethylene glycol 1000) succinate (TPGS). To obtain well-constructed clusters of iron oxide nanoparticles (IONPs), the synthetic parameters (the solvent systems and reaction temperature) were investigated. The rate of solvent evaporation is critical to optimise the formation of clusters which were spherical in shape, had a diameter of approximately 97 nm, and were highly stable for storage at room temperature. This greener synthetic approach displays the benefits of high yield and waste reduction compared to previous reports. In addition, IONP clusters of 50 μg mL−1 retained over 84% of the viability of KB cells and the structure of the clusters can be observed by transmission electron microscopy after cellular internalisation. The mechanism of cellular uptake of the IONP clusters was speculated to be via an energy-dependent endocytic pathway because the internalisation was significantly inhibited at 4 °C. These IONP clusters also had higher saturation magnetisation and r2 relaxation (253.85 s−1 mM−1) values and better T2-weighted contrast performance (r2/r1 = 20.5) than commercial Resovist®. The contrast signal for magnetic resonance imaging was efficiently increased by the IONP clusters in vivo, especially in the liver and tumour regions. Iron staining of both tissues confirmed the accumulation of the nanoparticles in both areas. Thus, these clusters, which were prepared with the use of a nonionic polymer surfactant, can potentially serve as efficient contrast agents for magnetic resonance applications.