Environmental
pollution with plastic polymers has become a global
problem, leaving no continent and habitat unaffected. Plastic waste
is broken down into smaller parts by environmental factors, which
generate micro- and nanoplastic particles (MNPPs), ultimately ending
up in the human food chain. Before entering the human body, MNPPs
make their first contact with saliva in the human mouth. However,
it is unknown what proteins attach to plastic particles and whether
such protein corona formation is affected by the particle’s
biophysical properties. To this end, we employed polystyrene MNPPs
of two different sizes and three different charges and incubated them
individually with saliva donated by healthy human volunteers. Particle
zeta potential and size analyses were performed using dynamic light
scattering complemented by nanoliquid chromatography high-resolution
mass spectrometry (nLC/HRMS) to qualitatively and quantitatively reveal
the protein soft and hard corona for each particle type. Notably,
protein profiles and relative quantities were dictated by plastic
particle size and charge, which in turn affected their hydrodynamic
size, polydispersity, and zeta potential. Strikingly, we provide evidence
of the latter to be dynamic processes depending on exposure times.
Smaller particles seemed to be more reactive with the surrounding
proteins, and cultures of the particles with five different cell lines
(HeLa, HEK293, A549, HepG2, and HaCaT) indicated protein corona effects
on cellular metabolic activity and genotoxicity. In summary, our data
suggest nanoplastic size and surface chemistry dictate the decoration
by human saliva proteins, with important implications for MNPP uptake
in humans.