Blood Half-Life Study of Magnetic Fluorescent Silica Nanoparticles by Using MR T2 Relaxation Measurement: Long Circulating SPIO

Iron-oxide-based nanoparticles have been used as MRI contrast agents because of their T-2 and T-2(*) shortening effect properties. Recently, we developed a material consisting of magnetic and fluorescent silica-coated nano-particles (MFSNs) that incorporated rhodamine isothiocyanate (RITC). A commercial and conventional T-2 contrast agent is coated with a hydrophilic polymer, like dextran or carboxymethyl dextran, to reduce bio-toxicity and to increase biocompatibility. In contrast, our MFSN is surface-modified with silica and polyethyleneglycol (PEG) to make it biocompatible and water-soluble. The MFSN has multi-modal magnetic and fluorescent properties. Therefore it can be used in confocal imaging, as well as magnetic resonance imaging (MRI). Various applications of this useful material in the biological and medical fields are strongly expected. For such applications, various physical and biological properties, like size, T-2 relaxivity (r(2)) and blood half-life (T-1/2), have to be studied in advance. In the present study, a transmission electron microscope (TEM) was used to measure the characteristics of MFSN. The average size of the MFSN particles is about, 70 nm and the MFSN is categorized as a superparamagnetic iron oxide (SPIO). The r(2) is similar to 130 mM(-1)s(-1) (Fe), as big as the value for commercial SPIO agents. The blood half-life (T-1/2 similar to 2.5 hours), as measured by using nuclear magnetic resonance (NMR) spin-spin relaxation, was much longer than for conventional SPIO agents as a result of PEGylation. This study is the first report of a "long circulating SPIO" with a big hydrophilic size and a long blood half-life. In conclusion, MFSN, with its property of long circulation, may be a good agent for macrophage imaging at a specific inflammation site, for tumor imaging and for cellular labeling.