Toxicological Comparison between Gold Nanoparticles in Different Shapes: Nanospheres Exhibit Less Hepatotoxicity and Lipid Dysfunction and Nanotriangles Show Lower Neurotoxicity

Gold nanoparticles (AuNPs) in different shapes have been developed and investigated for the treatment of various diseases. However, the potential toxicological vulnerability of different organs to morphologies of AuNPs and the complication of the toxicological profile of AuNPs by other health risk factors (e.g., plastic particles) have rarely been investigated systematically. Therefore, in this study, we aimed to investigate the toxicological differences between the spherical and triangular AuNPs (denoted as AuS and AuT, respectively) and the toxicological modulations by micro- or nanosized polystyrene plastic particles (denoted as mPS and nPS, respectively) in mice. Systemic biochemical characterizations were performed after a 90 day oral gavage feeding to obtain toxicological comparisons in different organs. In the case of single exposure to gold nanoparticles, AuT was associated with significantly higher aspartate amino-transferase (168.2%, <i>P</i> < 0.05), superoxide dismutase (183.6%, <i>P</i> < 0.001), catalase (136.9%, <i>P</i> < 0.01), total cholesterol (132.6%, <i>P</i> < 0.01), high-density lipoprotein cholesterol (131.3%, <i>P</i> < 0.05), and low-density lipoprotein cholesterol (204.6%, <i>P</i> < 0.01) levels than AuS. In contrast, AuS was associated with a significantly higher nitric oxide level (355.1%, <i>P</i> < 0.01) than AuT. Considering the overall toxicological profiles in single exposure and coexposure with multiscale plastics, it has been found that AuS is associated with lower hepatotoxicity and lipid metabolism malfunction, and AuT is associated with lower neurotoxicity than AuS. This finding may facilitate the future therapeutic design by considering the priority in protections of different organs and utilizing appropriate material morphologies.