Identifying Trends in Gold Nanoparticle Toxicity and Uptake: Size, Shape, Capping Ligand, and Biological Corona

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.