Monophosphonic versus Multiphosphonic Acid Based PEGylated Polymers for Functionalization and Stabilization of Metal (Ce, Fe, Ti, Al) Oxide Nanoparticles in Biological Media

Abstract

Over the last decade, engineered nanoparticles have been developed as therapeutic, diagnostic, and theranostic agents, leading to the development of nanomedicine.[1–5] Recent studies have shown however that nanomedicine has not met the initial expectations regarding translation to the clinics. In a literature survey, Wilhelm et al. have found that with regard For applications in nanomedicine, particles need to be functionalized to prevent protein corona formation and/or aggregation. Most advanced strategies take advantage of functional polymers and assembly techniques. Nowadays there is an urgent need for coatings that are tailored according to a broad range of surfaces and that can be produced on a large scale. Herein, we synthesize monophosphonic and multiphosphonic acid based poly(ethylene glycol) (PEG) polymers with the objective of producing efficient coats for metal oxide nanoparticles. Cerium, iron, titanium, and aluminum oxide nanoparticles of different morphologies (spheres, platelets, nanoclusters) and sizes ranging from 7 to 40 nm are studied in physiological and in protein rich cell culture media. It is found that the particles coated with monofunctionalized polymers exhibit a mitigated stability over time (<1 week), whereas the multifunctionalized copolymers provide resilient coatings and long-term stability (> months). With the latter, PEG densities in the range 0.2–0.5 nm−2 and layer thickness about 10 nm provide excellent performances. The study suggests that the proposed coating allows controlling nanomaterial interfacial properties in biological environments. PEGylated Metal Oxide Nanoparticles