The drive behind the growing interest
in understanding gold nanoparticle
(AuNP) cytotoxicity originates from the promise of AuNPs for diverse
biological applications across the fields of drug delivery, biosensing,
biological imaging, gene therapy, and photothermal therapy. Although
we continue to investigate the novel biomedical applications of AuNPs,
progress is currently stalled at the periphery of understanding the
forces that govern critical nano–bio interactions. In this
work, we systematically probe the size, shape, and surface capping
effects of nanogold by designing a set of eight unique AuNPs. This
allowed us to undertake a systematic study involving each of these
parameters in the context of their influence on the cytotoxicity and
cellular uptake by human prostate cancer cells (PC3) as a model biological
system. While studying the influence of these parameters, our study
also investigated the influence of serum proteins in forming different
levels of biological corona on AuNPs, thereby further influencing
the nano–bio interface. As such, increased cellular uptake
(by nanoparticle number) was observed with decreasing the AuNP size
and increased uptake levels were observed for gold nanospheres (of
the same size) stabilized with amino acids compared to citrate or
cetyltrimethylammonium bromide (CTAB). Spherical particles were found
to be taken up in greater numbers compared to the shapes with broad
flat faces. When measuring cytotoxicity, CTAB-stabilized rod- and
cube-shaped particles were well tolerated by the cells, whereas toxicity
was observed in the case of CTAB-stabilized spherical and prismatic
particles. These effects, however, are underpinned by different mechanisms.
Further, it is demonstrated that it is possible for different chemical
stabilizers to elicit varied cytotoxic effects. Although we find the
limited role of serum proteins in mediating toxicity, they do play
a critical role in influencing the cellular uptake of AuNPs, with
lower levels of uptake generally observed in the presence of serum.
Our findings offer a useful step in the direction of predicting the
biological interactions of AuNPs based on specific parameters of the
AuNP design.