Size-Dependent Interactions of Degraded PET Nanoparticles with Human Serum Albumin: Thermodynamic and Molecular Insights

This study examines the interaction between degraded
polyethylene
terephthalate (PET) nanoparticles and human serum albumin (HSA), focusing
on the effects of nanoparticle size and surface modifications resulting
from degradation. PET degradation, induced via shock compression in
water, leads to significant chemical alterations, including the formation
of hydroxyl, carboxyl, and carbonyl groups. These modifications influence
the hydrophilicity of PET nanoparticles and their binding behavior
with HSA. The production of degraded PET nanoparticles involves subjecting
pristine PET to controlled shock compression in an aqueous environment,
which initiates chemical reactions similar to those that may occur
during degradation. The degradation process is characterized by a
progressive breakdown of polymer chains, leading to an increase in
functionalized surface groups that enhanced hydrophilicity. The performed
analysis of surface chemistry reveals that the introduction of oxygen-containing
groups alters the interaction properties of PET nanoparticles, making
them more prone to hydrogen bonding with water molecules while simultaneously
reducing their affinity for HSA binding. Molecular dynamics simulations,
umbrella sampling, and weighted histogram analysis are employed to
investigate the thermodynamic aspects of PET-HSA interactions. The
study identifies preferred binding sites of PET nanoparticles on HSA,
revealing that degraded PET nanoparticles preferentially bind to Domain
I and Domain III of HSA. Interaction energy analysis demonstrates
that larger PET nanoparticles exhibit stronger binding, whereas small
degraded nanoparticles have significantly reduced interaction energies,
indicating a higher likelihood of desorption. Further structural analysis
using root-mean-squared deviation (RMSD) and root-mean-squared fluctuation
(RMSF) confirms that PET binding does not significantly alter HSA’s
secondary structure. However, degradation significantly increases
PET hydrophilicity, weakening their adsorption onto HSA. Large PET
nanoparticles are strongly bound, whereas small degraded nanoparticles
remain unbound, raising concerns regarding their potential toxicity
due to free migration in the bloodstream. These findings provide crucial
insights into the biological implications of PET degradation, the
role of surface chemistry in determining nanoparticle interactions,
and their potential contributions to nanoplastic toxicity.