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

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 mono- and multi-phosphonic 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 mono-functionalized polymers exhibit a mitigated stability over time, whereas the multi-functionalized 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.