Surface Modification of Gadolinium Oxide Thin Films and Nanoparticles using Poly(ethylene glycol)-Phosphate

The performance of nanomaterials for biomedical applications is highly dependent on the nature and the quality of surface coatings. In particular, the development of functionalized nanoparticles for magnetic resonance imaging (MRI) requires the grafting of hydrophilic, nonimmunogenic, and biocompatible polymers such as poly(ethylene glycol) (PEG). Attached at the surface of nanoparticles, this polymer enhances the steric repulsion and therefore the stability of the colloids. In this study, phosphate molecules were used as an alternative to silanes or carboxylic acids, to graft PEG at the surface of ultrasmall gadolinium oxide nanoparticles (US-Gd₂O₃, 2–3 nm diameter). This emerging, high-sensitivity “positive” contrast agent is used for signal enhancement in <i>T</i>₁-weighted molecular and cellular MRI. Comparative grafting assays were performed on Gd₂O₃ thin films, which demonstrated the strong reaction of phosphate with Gd₂O₃ compared to silane and carboxyl groups. Therefore, PEG-phosphate was preferentially used to coat US-Gd₂O₃ nanoparticles. The grafting of this polymer on the particles was confirmed by XPS and FTIR. These analyses also demonstrated the strong attachment of PEG-phosphate at the surface of Gd₂O₃, forming a protective layer on the nanoparticles. The stability in aqueous solution, the relaxometric properties, and the MRI signal of PEG-phosphate-covered Gd₂O₃ particles were also better than those from non-PEGylated nanoparticles. As a result, reacting PEG-phosphate with Gd₂O₃ particles is a promising, rapid, one-step procedure to PEGylate US-Gd₂O₃ nanoparticles, an emerging “positive” contrast agent for preclinical molecular and cellular applications