We have introduced isothermal titration calorimetry (ITC) to probe protein binding to polymer-grafted nanoparticles. ITC is sensitive enough to analyze the weak (soft corona) binding of less than one protein per particle. It provides quantitative measurements of the average number of proteins and the strength of their binding interactions. Monodisperse iron oxide nanoparticles can be grafted with very dense and stable polymer brushes using nitrodopamine anchor chemistry. This allows us to explore the effect of nanoparticle size, curvature, polymer shell chemistry, and polymer shell topology on their interaction with proteins. We have applied this to explore the limits of polymer brushes of poly(ethylene glycol), poly(2-alkyl-2-oxazoline), and poly(N-isopropyl acrylamide) to avoid adsorption of a protein corona on nanoparticles in the size range of 5-15 nm. Correctly designed, these particles have been thought to be stealth, i.e., not interacting with proteins and cells non-specifically. The ultra-sensitive ITC measurements show weak but significant binding of some blood proteins to nanoparticles densely grafted with linear polymer brushes. We show which type of blood serum proteins and protein properties bind to the particles despite the protective polymer shell. The protein adsorption strongly depends on the polymer brush grafting density also for very high grafting densities; it is less dependent on polymer chain length due to the high curvature of small nanoparticles. We also report the first results on the complete suppression of protein adsorption on polymer-grafted nanoparticles using such ultra-sensitive measurements of protein interactions. Full suppression of protein adsorption was only observed for nanoparticles densely grafted with cyclic poly(2-ethyl-2-oxazoline), which had the highest polymer segment density close to the core.

Protein corona formation on polymer-grafted nanoparticles probed with ITC shows the superiority of cyclic polymer brushes

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.