Polyethylene glycol backfilling mitigates the negative impact of the protein corona on nanoparticle cell targeting

Qin Dai, Carl Walkey, Warren CW Chan

Angewandte Chemie International Edition, Volume 53, Issue 20 | DOI: 10.1002/anie.201309464


In protein‐rich environments such as the blood, the formation of a protein corona on receptor‐targeting nanoparticles prevents target recognition. As a result, the ability of targeted nanoparticles to selectively bind to diseased cells is drastically inhibited. Backfilling the surface of a targeted nanoparticle with polyethylene glycol (PEG) molecules is demonstrated to reduce the formation of the protein corona and re‐establishes specific binding. The length of the backfilled PEG molecules must be less than the length of the ligand linker; otherwise, PEG interferes with the binding of the targeting ligand to its corresponding cellular receptor.