Paper: Core-shell particles really are invisible to cells

In a recent research paper, we have tried to shed light on a few questions that are holding back the development of nanoparticles for medicine. Can nanoparticles really be made “stealth” for cells in the body? Are there mechanical mechanisms induced by the constant flow of body fluids that aid the detection and uptake of nanoparticles? Is the weak correlation between lab and in vivo results due to the choice of too simplified cell systems?

Nanoparticles with dense shells of hydrated polymers have been in clinical use since the 1990s. Since then, they have become workhorses in modern medicine in the form of imaging contrast agents and drug delivery vehicles. They are also increasingly being used for therapy and theranostics. Although unsurpassed in performance, their efficacy has fallen short of expectations.

Researchers at the Institute for Biologically Inspired Materials (BIMat) are searching for the missing understanding that would make it possible to improve nanoparticles used in medicine. This research is made possible by exquisitely well-defined model systems developed in an ERC project. Such model systems allow for investigating individual parameters in the interaction of nanoparticles and cells.

In our recent publication “Poly(ethylene glycol) Grafting of Nanoparticles Prevents Uptake by Cells and Transport Through Cell Barrier Layers Regardless of Shear Flow and Particle Size” in ACS Biomaterials Science & Engineering, we showed that small nanoparticles with dense poly(ethylene glycol) brushes are not taken up by cells or passing between cells in epithelial barrier layers. These results were independent of the investigated cell types, which covered a broad range of cells relevant to the tissues that are known to be exposed to nanoparticles in this size range. Furthermore, we showed that mechanical stimuli in the form of shear flow did not influence cell uptake, as had been indicated in some previous studies using particles of larger size.

The results mean that significant improvements can be made for nanoparticles in clinical use if they are synthesized with a dense and stable polymer brush of sufficient thickness to avoid adsorption of a hard protein corona to the particle surface.