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Sci Rep. 2019 Mar 13;9(1):4366. doi: 10.1038/s41598-019-40579-6.

Cationic gold nanoparticles elicit mitochondrial dysfunction: a multi-omics study.

Author information

1
Nanosafety & Nanomedicine Laboratory, Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.
2
Department of Medical Biochemistry & Biophysics, Karolinska Institutet, 171 77, Stockholm, Sweden.
3
Department of Biosciences & Nutrition, Karolinska Institutet, 141 83, Huddinge, Sweden.
4
Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.
5
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO, 80309, USA.
6
CICbiomaGUNE, 20009, San Sebastian, Spain.
7
ISM, UMR CNRS 5255, Université de Bordeaux, 33405, Talence, France.
8
Nanosafety & Nanomedicine Laboratory, Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden. Bengt.Fadeel@ki.se.

Abstract

Systems biology is increasingly being applied in nanosafety research for observing and predicting the biological perturbations inflicted by exposure to nanoparticles (NPs). In the present study, we used a combined transcriptomics and proteomics approach to assess the responses of human monocytic cells to Au-NPs of two different sizes with three different surface functional groups, i.e., alkyl ammonium bromide, alkyl sodium carboxylate, or poly(ethylene glycol) (PEG)-terminated Au-NPs. Cytotoxicity screening using THP-1 cells revealed a pronounced cytotoxicity for the ammonium-terminated Au-NPs, while no cell death was seen after exposure to the carboxylated or PEG-modified Au-NPs. Moreover, Au-NR3+ NPs, but not the Au-COOH NPs, were found to trigger dose-dependent lethality in vivo in the model organism, Caenorhabditis elegans. RNA sequencing combined with mass spectrometry-based proteomics predicted that the ammonium-modified Au-NPs elicited mitochondrial dysfunction. The latter results were validated by using an array of assays to monitor mitochondrial function. Au-NR3+ NPs were localized in mitochondria of THP-1 cells. Moreover, the cationic Au-NPs triggered autophagy in macrophage-like RFP-GFP-LC3 reporter cells, and cell death was aggravated upon inhibition of autophagy. Taken together, these studies have disclosed mitochondria-dependent effects of cationic Au-NPs resulting in the rapid demise of the cells.

PMID:
30867451
DOI:
10.1038/s41598-019-40579-6
Free PMC Article

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