Preventing corona effects: multi-phosphonic acid poly(ethylene glycol) copolymers for stable stealth iron oxide nanoparticles

TL;DR

This paper develops phosphonic acid poly(ethylene glycol) copolymer coatings for iron oxide nanoparticles, significantly reducing protein corona formation and cellular uptake, thus enhancing stability and potential for biomedical applications.

Contribution

It introduces a novel, scalable coating strategy using multi-phosphonic acid PEG copolymers that outperform existing coatings in stability and low cellular uptake.

Findings

Coatings with multiple phosphonic acid groups improve nanoparticle stability.

PEGylated particles show extremely low cellular uptake (~100 femtograms per cell).

Surface chemistry is crucial in nanoparticle-cell interactions.

Abstract

When disperse in biological fluids, engineered nanoparticles are selectively coated with proteins, resulting in the formation of a protein corona. It is suggested that the protein corona is critical in regulating the conditions of entry into the cytoplasm of living cells. Recent reports describe this phenomenon as ubiquitous and independent of the nature of the particle. For nanomedicine applications however, there is a need to design advanced and cost-effective coatings that are resistant to protein adsorption and that increase the biodistribution in vivo. In this study, phosphonic acid poly(ethylene glycol) copolymers were synthesized and used to coat iron oxide particles. The copolymer composition was optimized to provide simple and scalable protocols as well as long-term stability in culture media. It is shown that polymers with multiple phosphonic acid functionalities and PEG chains outperform other types of coating, including ligands, polyelectrolytes and carboxylic acid functionalized PEG. PEGylated particles exhibit moreover exceptional low cellular uptake, of the order of 100 femtograms of iron per cell. The present approach demonstrates that the surface chemistry of engineered particles is a key parameter in the interactions with cells. It also opens up new avenues for the efficient functionalization of inorganic surfaces.