In this work, poly(N-isopropyl acrylamide-co-acrylamide) [P(NIPAAm-co-AAm)] nanogels were modified by hydrolysis above the lower critical solution temperature (LCST) to localize carboxylic acid functional groups at the surface (surface hydrolysis). PNIPAAm copolymerized with 15% and 20% nominal AAm in the feed were prepared and compared to equivalent hydrogels with acrylic acid. The effect and extent of surface hydrolysis was confirmed by potentiometric titration and zeta potential. These surface modified nanogels were then modified with primary amine functionalized PEG chains. Surface hydrolysis-mediated PEGylation had little effect on the swelling response of the nanogels, while also preventing adsorption of model proteins in physiological relevant conditions. While both 15% and 20% AAm gels both decreased protein adsorption, only the 20% AAm gels resulted in fully preventing protein adsorption. The results presented here point to surface hydrolysis as a new route to passivate nanogels for use in vivo.
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