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. 2024 Oct 9;9(42):42990-43004.
doi: 10.1021/acsomega.4c05961. eCollection 2024 Oct 22.

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

Lan Zhang  1 , Yuyang Ma  1   2 , Zhiliang Wei  3 , Qian Li  1
Affiliations

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

Lan Zhang et al. ACS Omega. .

Abstract

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%, P < 0.05), superoxide dismutase (183.6%, P < 0.001), catalase (136.9%, P < 0.01), total cholesterol (132.6%, P < 0.01), high-density lipoprotein cholesterol (131.3%, P < 0.05), and low-density lipoprotein cholesterol (204.6%, P < 0.01) levels than AuS. In contrast, AuS was associated with a significantly higher nitric oxide level (355.1%, P < 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.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Schematic diagram of the experimental design.
Figure 2
Figure 2
Basic characterizations of AuNPs and PS particles used in this study. TEM images (a,b) and extinction spectra (c,d) of AuS and AuT. SEM images of nPS (e) and mPS (f).
Figure 3
Figure 3
H&E staining (a–d) and organ coefficients (e–j) in the single exposure to AuNPs. H&E stained images of liver (a,b) and kidney (c,d) for the AuS and AuT groups. Yellow and blue arrows denoted inflammatory cell infiltration. Comparisons of organ coefficients between AuS and AuT in the liver (e), kidney (f), brain (g), heart (h), lung (i), and spleen (j). ***P < 0.001.
Figure 4
Figure 4
Biochemical markers in a single exposure to AuNPs. Hepatotoxicity was assessed by ALT (a), AST (b), SOD (c), CAT (d), GSH (e), and MDA (f). Nephrotoxicity was evaluated by BUN (g) and CRE (h). Neurotoxicity was represented by AChE (i) and NO (j). Inflammatory perturbation was assessed by TNF-α (k), IL-1β (l), and IL-6 (m). Lipid metabolism dysfunction was evaluated by TG (n), T-CHO (o), HDL-C (p), and LDL-C (q). *P < 0.05, **P < 0.01, and ***P < 0.001.
Figure 5
Figure 5
Comparisons of gut microbiota between the AuS and AuT groups. Ace index (a), Chao index (b), Shannon index (c), and Simpson index (d) in gut microbiota after exposure to AuNPs; (e) Venn diagram for OTUs; (f) PCoA separation between the AuS and AuT groups; (g) dominant microbiotas at the family level; and (h) heatmap of gut microbial genes involved in diseases at Level 2 of the KEGG pathway annotation. *P < 0.05.
Figure 6
Figure 6
H&E staining (a–h) and organ coefficients (i–n) in the coexposures. H&E stained images of liver (a–d) and kidney (e–h) for the AuSnPS, AuTnPS, AuSmPS, and AuTmPS groups. Yellow and blue arrows denoted inflammatory cell infiltration. Comparisons of organ coefficients among the coexposure groups for the liver (e), kidney (f), brain (g), heart (h), lung (i), and spleen (j). *P < 0.05, **P < 0.01, and ***P < 0.001.
Figure 7
Figure 7
Biochemical markers in the coexposure to AuNPs and PS particles. Hepatotoxicity was assessed by ALT (a), AST (b), SOD (c), CAT (d), GSH (e), and MDA (f). Nephrotoxicity was evaluated by BUN (g) and CRE (h). Neurotoxicity was represented by AChE (i) and NO (j). Inflammatory perturbation was assessed by TNF-α (k), IL-1β (l), and IL-6 (m). Lipid metabolism dysfunction was evaluated by TG (n), T-CHO (o), HDL-C (p), and LDL-C (q). *P < 0.05, **P < 0.01, and ***P < 0.001.
Figure 8
Figure 8
Comparisons of gut microbiota among the groups with coexposures. Ace index (a), Chao index (b), Shannon index (c), and Simpson index (d) in gut microbiota after coexposures; (e) Venn diagram for OTUs; (f) dominant microbiotas at the family level; (g) heatmap of gut microbial genes involved in diseases at the Level 2 of the KEGG pathway annotation. *P < 0.05.
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