In the last few years, zwitterionic polymers have been developed as antifouling surface coatings. However, their ability to completely suppress protein adsorption at the surface of nanoparticles (NPs) in complex biological media remains undemonstrated. We have developed several polymeric zwitterionic nanoparticle ligands and investigated the formation of hard (irreversible) and soft (reversible) protein corona around fluorescent quantum dots (QDs) as model nanoparticles coated with sulfobetaine (SB), phosphorylcholine (PC) and carboxybetaine (CB) in model albumin solutions and in whole serum. We show for the first time a complete absence of protein corona around SB-coated NPs, while PC- CB-or PEG-coated NPs undergo reversible adsorption or partial aggregation. Single NP tracking in the cytoplasm of live cells corroborate these in vitro observations. This absence of protein adsorption was also tested on other nanomaterials, including iron oxide and gold NPs.
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