Anti-fouling magnetic nanoparticles for siRNA delivery

Abstract

Iron oxide nanoparticles (IONPs), with a diameter of 8 nm, have been coated with two different polymers, i.e. poly(oligoethylene glycol) methyl ether acrylate (P(OEG-A)) and poly(dimethylaminoethyl acrylate) (P(DMAEA)). The polymers were attached to the nanoparticle surface using two different strategies, with the aim of creating an internal layer of P(DMAEA) and an outer shell of P(OEG-A). The subsequent polymer-stabilized IONPs were characterized using ATR, XPS and TGA, proving the presence of polymers on the IONP surfaces with a grafting density ranging from 0.05 to 0.22 chain per nm². High grafting densities were demonstrated when the two homopolymers were assembled on the surfaces of the IONPs simultaneously. The polymer composition at the surfaces of the IONPs could be controlled by manipulating the feed ratio P(OEG-A)–P(DMAEA) present in solution. These hybrid organic–inorganic particles (70–150 nm) proved to be stable in both water and 50 vol% fetal bovine serum (FBS). In addition, zeta-potential measurements confirmed that P(OEG-A) chains effectively mask the positive charge originating from P(DMAEA) thereby limiting protein adsorption on these particles. Hybrid nanoparticles were exploited for the complexation of siRNA, thereby generating IONP siRNA nano-carriers with anti-fouling P(OEG-A) shells. The transfection efficiency was measured using human neuroblastoma SHEP cells both in the presence and in the absence of a magnetic field in FBS. The transfection efficiency was determined by both fluorescence microscopy and flow cytometry. Cytotoxicity studies revealed that the IONP carriers were non-toxic to SHEP cells. In addition, studies on the proton transverse relaxation enhancement properties of these stabilized IONPs indicated high relaxivities (∼160 s⁻¹ per mM of Fe).