There has been much interest in integrating various inorganic
nanoparticles
(nanoscale colloids) in biology and medicine. However, buildup of
a protein corona around the nanoparticles in biological media, driven
by nonspecific interactions, remains a major hurdle for the translation
of nanomedicine into clinical applications. In this study, we investigate
the interactions between gold nanoparticles and serum proteins using
a series of dihydrolipoic acid (DHLA)-based ligands. We employed gel
electrophoresis combined with UV–vis absorption and dynamic
light scattering to correlate protein adsorption with the nature and
size of the ligand used. For instance, we found that AuNPs capped
with DHLA alone promote nonspecific protein adsorption. In comparison,
capping AuNPs with polyethylene glycol- or zwitterion-appended DHLA
essentially prevents corona formation, regardless of ligand charge
and size. Our results highlight the crucial role of surface chemistry
and core material in protein corona formation and offer valuable information
for the design of colloidal nanomaterials for biological applications.