Poly(ethylene glycol) Grafting of Nanoparticles Prevents Uptake by Cells and Transport Through Cell Barrier Layers Regardless of Shear Flow and Particle Size.

It has long been a central tenet of biomedical research that coating of nanoparticles with hydrated polymers can improve their performance in biomedical applications. However, the efficacy of the approach in vivo is still debated. In vitro model systems to test the performance of engineered nanoparticles for in vivo applications often use nonrepresentative cell lines and conditions for uptake and toxicity tests. We use our platform of monodisperse iron oxide nanoparticles densely grafted with nitrodopamide-poly(ethylene glycol) (PEG) to probe cell interactions with a set of cell types and culture conditions that are relevant for applications in which nanoparticles are injected into the bloodstream. In the past, these particles have proved to have excellent stability and negligible interaction with proteins and membranes under physiological conditions. We test the influence of flow on the uptake of nanoparticles. We also investigate the transport through endothelial barrier cell layers, as well as the effect that PEG-grafted iron oxide nanoparticles have on cell layers relevant for nanoparticles injected into the bloodstream. Our results show that the dense PEG brush and resulting lack of nonspecific protein and membrane interaction lead to negligible cell uptake, toxicity, and transport across barrier layers. These results contrast with far less well-defined polymer-coated nanoparticles that tend to aggregate and consequently strongly interact with cells, for example, by endocytosis.