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Open AccessArticle

A Metabolomic Approach for the In Vivo Study of Gold Nanospheres and Nanostars after a Single-Dose Intravenous Administration to Wistar Rats

UCIBIO/REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
LAQV/REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal
LAQV/REQUIMTE, Department of Drug Sciences, Laboratory of Pharmacology, Faculty of Pharmacy, University of Porto, 4150-755 Porto, Portugal
Authors to whom correspondence should be addressed.
Nanomaterials 2019, 9(11), 1606;
Received: 13 October 2019 / Revised: 5 November 2019 / Accepted: 6 November 2019 / Published: 12 November 2019
(This article belongs to the Special Issue Advances in Nanotoxicology)
Gold nanoparticles (AuNPs) are promising nanoplatforms for drug therapy, diagnostic and imaging. However, biological comparison studies for different types of AuNPs fail in consistency due to the lack of sensitive methods to detect subtle differences in the expression of toxicity. Therefore, innovative and sensitive approaches such as metabolomics are much needed to discriminate toxicity, specially at low doses. The current work aims to compare the in vivo toxicological effects of gold nanospheres versus gold nanostars (of similar ~40 nm diameter and coated with 11-mercaptoundecanoic acid) 24 h after an intravenous administration of a single dose (1.33 × 1011 AuNPs/kg) to Wistar rats. The biodistribution of both types of AuNPs was determined by graphite furnace atomic absorption spectroscopy. The metabolic effects of the AuNPs on their main target organ, the liver, were analyzed using a GC-MS-based metabolomic approach. Conventional toxicological endpoints, including the levels of ATP and reduced and oxidized glutathione, were also investigated. The results show that AuNPs preferentially accumulate in the liver and, to a lesser extent, in the spleen and lungs. In other organs (kidney, heart, brain), Au content was below the limit of quantification. Reduced glutathione levels increased for both nanospheres and nanostars in the liver, but ATP levels were unaltered. Multivariate analysis showed a good discrimination between the two types of AuNPs (sphere- versus star-shaped nanoparticles) and compared to control group. The metabolic pathways involved in the discrimination were associated with the metabolism of fatty acids, pyrimidine and purine, arachidonic acid, biotin, glycine and synthesis of amino acids. In conclusion, the biodistribution, toxicological, and metabolic profiles of gold nanospheres and gold nanostars were described. Metabolomics proved to be a very useful tool for the comparative study of different types of AuNPs and raised awareness about the pathways associated to their distinct biological effects. View Full-Text
Keywords: gold nanoparticles (AuNPs); shape; biodistribution; metabolomics; toxicity; in vivo gold nanoparticles (AuNPs); shape; biodistribution; metabolomics; toxicity; in vivo
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MDPI and ACS Style

Enea, M.; Araújo, A.M.; Peixoto de Almeida, M.; Soares, M.E.; Gonçalves-Monteiro, S.; Guedes de Pinho, P.; Pereira, E.; Bastos, M.L.; Carmo, H. A Metabolomic Approach for the In Vivo Study of Gold Nanospheres and Nanostars after a Single-Dose Intravenous Administration to Wistar Rats. Nanomaterials 2019, 9, 1606.

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