Protein Corona-Mediated Inhibition of Nanozyme Activity: Impact of Protein Shape

During
biomedical applications, nanozymes, exhibiting
enzyme-like
characteristics, inevitably come into contact with biological fluids
in living systems, leading to the formation of a protein corona on
their surface. Although it is acknowledged that molecular adsorption
can influence the catalytic activity of nanozymes, there is a dearth
of understanding regarding the impact of the protein corona on nanozyme
activity and its determinant factors. In order to address this gap,
we employed the AuNR@Pt@PDDAC [PDDAC, poly(diallyldimethylammonium
chloride)] nanorod (NR) as a model nanozyme with multiple activities,
including peroxidase, oxidase, and catalase-mimetic activities, to
investigate the inhibitory effects of the protein corona on the catalytic
activity. After the identification of major components in the plasma
protein corona on the NR, we observed that spherical proteins and
fibrous proteins induced distinct inhibitory effects on the catalytic
activity of nanozymes. To elucidate the underlying mechanism, we uncovered
that the adsorbed proteins assembled on the surface of the nanozymes,
forming protein networks (PNs). Notably, the PNs derived from fibrous
proteins exhibited a screen mesh-like structure with smaller pore
sizes compared to those formed by spherical proteins. This structural
disparity resulted in a reduced efficiency for the permeation of substrate
molecules, leading to a more robust inhibition in activity. These
findings underscore the significance of the protein shape as a crucial
factor influencing nanozyme activity. This revelation provides valuable
insights for the rational design and application of nanozymes in the
biomedical fields.