“Nanocubes in Nanocubes”: Using self-assembly to enhance the performance of
D. Acharya, G. Zhen, B. Muir, P. Hartley, L. Waddington, B. Moffat, P. Mulvaney
CSIRO Molecular Health Technology, AU
Keywords: biosensor, diagnostics
Abstract:Colloidal superparamagnetic iron oxide (SPIO) nanoparticles possess unique magnetic properties and their ability to shorten the effective transverse relaxation time (T2) during magnetic resonance imaging (MRI) makes them excellent contrast agents, as well as X-ray contrast agents. Their biocompatibility and ease of synthesis have made them an attractive choice in the clinic, however, there are issues in terms of their suboptimal biodistribution, poor blood half life which limits the ‘imaging window’ and they tend to show very slow clearance from the body. In this context we investigated the application of lyotropic liquid crystalline mesophase as a delivery vehicle for the SPIOs. Polar lipids such as glycerol monooleate and phytantriol are known to form various lyotropic phases when mixed with water. The bicontinuous cubic phase with reversed curvature is of particular interest and forms at sufficiently high concentration of water and room temperature. Furthermore this mesophase can be homogenised to form stable dispersions called cubosomes in presence of suitable emulsifiers.This study looks at the characterisation and performance of these cubosomes loaded with iron oxide for the diagnostic imaging field. This is a novel approach and one that leads to significant promise in this field. Various preparations of cubosomes loaded with SPIOs of different shape and size have been characterised in this study. Figure 1 illustrates materials with a high degree of regularity resulting from the nano-scale porosity of the self assembled matrix, and high internal and external surface area. This regularity and high loading of contrast agent results in enhanced T2 relaxation rates, see Figure 2. Imaging studies in mice brain were performed and the results, such as those of Figure 3, demonstrate good Xray phase contrast. Other MRI studies in mice have shown rapid clearance to the liver. In conclusion we have developed a novel, self assembling approach for the loading, delivery and imaging of nanoparticulate materials in vivo.