Polymer Topology Determines the Formation of Protein Corona on Core–Shell Nanoparticles

[Image: see text] Linear and cyclic poly(2-ethyl-2-oxazoline) (PEOXA) adsorbates provide excellent colloidal stability to superparamagnetic iron oxide nanoparticles (Fe(x)O(y) NPs) within protein-rich media. However, dense shells of linear PEOXA brushes cannot prevent weak but significant attractive interactions with human serum albumin. In contrast, their cyclic PEOXA counterparts quantitatively hinder protein adsorption, as demonstrated by a combination of dynamic light scattering and isothermal titration calorimetry. The cyclic PEOXA brushes generate NP shells that are denser and more compact than their linear counterparts, entirely preventing the formation of a protein corona as well as aggregation, even when the lower critical solution temperature of PEOXA in a physiological buffer is reached.