Surface modified superparamagnetic iron oxide nanoparticles (SPIONs) for high efficiency folate-receptor targeting with low uptake by macrophages

Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) designed to interact with tumor cells have received increasing interest in the past few years, due to their potential for applications such as magnetic resonance imaging (MRI) contrast enhancement, drug delivery, and hyperthermia. However, the stability of these nanoparticles under physiological conditions, and their ability to selectively target tumor cells are challenges which need to be addressed. In this work, SPIONs were first modified with poly(glycidyl methacrylate) (PGMA) via atom transfer radical polymerization (ATRP). The epoxy groups in PGMA were then reacted with ethylenediamine to generate amino groups, which were conjugated with different amounts of folic acid (FA) for cancer cells targeting. The as-synthesized folic acid conjugated SPIONs (SPIONs–PGMA–FA) are hydrophilic and highly stable in an aqueous medium. The targeting efficiency of the folic acid-conjugated nanoparticles was investigated with different cell lines. The uptake of SPIONs–PGMA–FA by KB (human epidermoid carcinoma) cells is about three and five times higher than that of macrophages and 3T3 fibroblasts, respectively. No significant cytotoxicity was observed when the three types of cells were incubated with nanoparticles at a concentration of 0.5 mg mL⁻¹ or less. The nanoparticles also exhibited high MR enhancement effects with r₂ and r₂/r₁ values of 191.4 mM⁻¹ s⁻¹ and 98 respectively in a 3T magnetic field. Hence, these nanoparticles can potentially be used to selectively target cancer cells for imaging as well as hyperthermia.