Grafting of P(OEGA) Onto Magnetic Nanoparticles Using Cu(0) Mediated Polymerization: Comparing Grafting “from” and “to” Approaches in the Search for the Optimal Material Design of Nanoparticle MRI Contrast Agents

Abstract

Superparamagnetic iron oxide nanoparticles (IONPs) have been studied extensively as negative contrast agents to enhance MRI efficacy. For optimal effective clinical use in T2/T2* weighted MRI imaging, the aim is to maximize relaxivity (r2) of IONPs, and minimize r1 relaxivity. A prerequisite for successful clinical use of magnetic nanoparticles is colloidal stability in biologically relevant media; biocompatible polymers with antifouling properties such as poly(ethylene glycol) (PEG) can be coated on the surface of IONPs, to improve stability and to impart longer blood circulation times. Our research aim was to optimize IONPs for use as contrast agents by achieving high grafting density and therefore colloidal stability, while retaining the magnetic properties of the IONP core. To attain the optimal material design the chemical functionalities and chain length of the polymeric layer must be precisely controlled. In this paper we describe the synthesis of poly(oligoethylene glycol acrylate) (P(OEGA)) functionalized magnetic iron oxide nanoparticles (IONP) made using a grafting “from” approach. Cu(0)-mediated living radical polymerization (LRP) was used to grow polymer chains of predetermined length from the surface of prefunctionalized IONPs. The polymers chain were further extended via an iterative addition of the same (or another) monomer with high efficiency demonstrating the retention of polymer chain end functionality. IONPs with different lengths of the P(OEGA) layer were also synthesized using a grafting “to” approach as a comparison study. Colloidal stabilities and MRI relaxivites of functionalized IONPs were investigated in both water and fetal calf serum (FCS). The grafting “from” approach proved to be superior to the grafting “to” approach as we were able to produce polymer coated IONPs with much higher r2 / r1 relaxivity ratios in water. At 9.4 T, the r2/r1 relaxivity values that we attained were about 6-fold higher than the commercial, clinically used, MRI contrast agent Resovist.