  Recent surveys have shown that the number of nanoparticle-based formulations
actually used at the clinical level is significantly lower than expected a
decade ago. One reason for this is that the nanoparticle physicochemical
properties fall short for handling the complexity of biological environments
and for preventing nonspecific protein adsorption. In this study, we address
the issue of the interactions of plasma proteins with polymer coated surfaces.
To this aim, we use a non-covalent grafting-to method to functionalize iron
oxide sub-10 nm nanoparticles and iron oxide flat substrates, and compare their
protein responses. The functionalized copolymers consist in alternating
poly(ethylene glycol) (PEG) chains and phosphonic acid grafted on the same
backbone. Quartz Crystal Microbalance with dissipation was used to monitor the
polymer adsorption kinetics and to evaluate the resistance to protein
adsorption. On flat substrates, functionalized PEG copolymers adsorb and form a
brush in the moderate or in the highly stretched regimes, with density between
0.15 and 1.5 nm-2. PEG layers using phosphonic acid as linkers exhibit
excellent protein resistance. In contrast, layers prepared with carboxylic acid
as grafting agent exhibit mitigated protein responses and layer
destructuration. The present study establishes a correlation between the
long-term stability of PEG coated particles in biofluids and the protein
resistance of surfaces coated with the same polymers.
