Abstract
The interaction of nanoparticles (NPs) with biological environments triggers the formation of a protein corona (PC), which significantly influences their behaviour in vivo. This review explores the evolving understanding of PC formation, focusing on the opportunity for decreasing or suppressing protein-NP interactions by macromolecular engineering of NP shells. The functionalization of NPs with a dense, hydrated polymer brush-shell is a powerful strategy to impart stealth properties in order to elude recognition by the immune system. While poly(ethylene glycol) (PEG) has been extensively used for this purpose, concerns regarding its stability and immunogenicity have prompted exploration of alternative polymers. The stealth properties of brush shells can be enhanced by tailoring functionalities and structural parameters, including molar mass, grafting density and polymer topology. Determining correlations between these parameters and biopassivity has enabled to obtain polymer-grafted NPs with high colloidal stability and prolonged circulation time in biological media.