The development of stable aqueous suspensions of PEGylated SPIONs for biomedicalapplications

Abstract

We report here the development of stable aqueous suspensions of biocompatiblesuperparamagnetic iron oxide nanoparticles (SPIONs). These so-called ferrofluids are usefulin a large spectrum of modern biomedical applications, including novel diagnostic tools andtargeted therapeutics. In order to provide prolonged circulation times for the nanoparticlesin vivo, the initial iron oxide nanoparticles were coated with a biocompatible polymerpoly(ethylene glycol) (PEG). To permit covalent bonding of PEG to the SPION surface,the latter was functionalized with a coupling agent, 3-aminopropyltrimethoxysilane (APS).This novel method of SPION PEGylation has been reproduced in numerous independentpreparations. At each preparation step, particular attention was paid to determine thephysico-chemical characteristics of the samples using a number of analytical techniquessuch as atomic absorption, Fourier transform infrared (FT-IR) spectroscopy and Ramanspectroscopy, transmission electron microscopy (TEM), photon correlation spectroscopy(PCS, used for hydrodynamic diameter and zeta potential measurements) andmagnetization measurements. The results confirm that aqueous suspensions of PEGylatedSPIONs are stabilized by steric hindrance over a wide pH range between pH 4 and 10.Furthermore, the fact that the nanoparticle surface is nearly neutral is in agreementwith immunological stealthiness expected for the future biomedical applicationsin vivo.